A controlled study of Tourette syndrome. V. Depression and mania.

To evaluate the role of depression and mania in Tourette syndrome (TS), we have examined 246 TS patients, 17 attention-deficit disorder (ADD) patients, 15 patients with ADD associated with TS, and 47 controls, using (1) the standardized National Institutes of Mental Health Diagnostic Interview Schedule questions for a life history of major depression and/or mania and (2) a modified Beck depression score for evaluation of depression at the time of the examination. The results were combined into depression, Beck, and mania scores. Among the controls, 2.1% had a depression score greater than 9, and none had a score greater than 10. Among the TS patients, 22.9% had a score greater than 9 and the scores ranged up to the maximum of 18 (P less than .0005). None of the pure ADD patients had a score greater than 6, whereas 20% of the ADD-secondary-to-TS (ADD 2(0) TS) patients had scores greater than or equal to 9. Among grade 3 TS patients, 46.6% had scores greater than or equal to 9. There were no differences in the frequency of depression in the TS patients with or without ADD. Comparable results were obtained for the Beck depression score, except that the percent with a score greater than or equal to 8 was higher for the TS patients with ADD (23.7%) than for those without ADD (9.3%). There was a good correlation between the depression score and the Beck score (r = .63), but no correlation between the ADD-with-hyperactivity (ADDH) score and either the depression score (r = .086) or the Beck score (r = .077). Among the controls, none had a mania score greater than or equal to 4, compared with 19.1% of the total TS patients (P = less than .0005), 11.8% of the ADD patients (P = .002), and 26.6% of the ADD 2(0) TS patients (P = .0005). Although some of the mania questions would be expected to be answered positively by ADDH patients, the correlation coefficient between the ADDH scores and the mania scores was only moderate (r = .29), whereas the correlation with the depression score was much higher (r = .63). There was minimal correlation between the number of tics and either the depression score (r = .267) or the Beck score (r = .193). We conclude that depression and manic-depressive symptoms are common in TS patients and are an integral part of the disorder rather than being secondary to motor or vocal tics.     

Proportion of S-phase tumor cells measured by flow cytometry is an independent prognostic factor in meningioma tumors.

Meningiomas are tumors in arachnoid cells which represent up to one fifth of all intracranial tumors and up to a quarter of spinal neoplasias. Although meningiomas have classically been considered to be benign tumors, it has also been well-established that they show a heterogeneous clinical outcome. To the best of our knowledge no study has yet been performed in which the independent prognostic value of both DNA ploidy and cell cycle has been simultaneously assessed in a large series of meningioma tumors. The aim of the present study was to prospectively explore the prognostic value of DNA ploidy status and the proliferative rate of tumor cells in a series of 105 consecutive meningioma patients studied at diagnosis. Both the presence of DNA aneuploidy and the proportion of S-phase tumor cells were analyzed in all cases in fresh tumors obtained during diagnostic surgery. From the technical point of view, we followed the recommendations of the Consensus Conference on Flow Cytometry DNA Analysis held in October 1992. Our results show that meningioma tumors display a relatively low incidence of DNA aneuploidy (14%), and they usually show a low proliferative rate (mean percentage of S-phase cells of 1.3 +/- 0.3%). The presence of DNA aneuploidy was associated with a higher incidence of aggressive histopathologic subtypes (P = 0.045), a greater age (P = 0.009), location at the cerebral convexity (P = 0.004), and a greater proportion of S-phase cells (P = 0.005). In contrast, no significant association between the DNA ploidy status of meningioma patients and their disease-free survival was found (P = 0. 1). Regarding the proliferative activity of neoplastic cells, we found that a high proportion of S-phase cells (>1.8%) was associated with a significantly lower mean age (P = 0.007), aggressive histopathologic subtypes (P = 0.03), a higher incidence of DNA aneuploidy (P = 0.004), and a significantly shorter disease-free survival (P < 0.004). Multivariate analysis of prognostic factors showed that the proportion of S-phase tumor cells was the most powerful independent prognostic factor in meningioma patients (P = 0.02). In summary, we conclude that the proportion of S-phase tumor cells represents the individual parameter with the highest value for predicting disease-free survival in meningioma patients.     

Adenosine cyclic 3',5'-monophosphate and steroid production by small ovarian follicles from Booroola ewes with and without a fecundity gene

The tissue contents of adenosine cyclic 3',5'-monophosphate (cAMP) in freshly dissected follicles (0.13-1.00 mm diam.) were significantly higher in Booroola ewes containing a major fecundity gene (FF and F+ ewes) compared to those values in Booroolas with no copy of the gene (++ animals; P less than 0.025). After a 1 h incubation with LH + FSH, the respective proportions of follicles with a diameter of 0.13-0.52 mm (n = 288) and 0.53-1.00 mm (n = 271) that had synthesized greater than or equal to 0.6 pmol cAMP and greater than or equal to 1.0 pmol cAMP were significantly influenced by genotype (Booroola ewes homozygous for the F-gene, FF greater than heterozygous, F+ greater than ++; P less than 0.01 for both follicle size ranges). The contents of progesterone, androstenedione, testosterone and oestradiol-17 beta in minced ethanolic extracts of freshly dissected follicles (n = 188) were undetectable regardless of Booroola genotype. However, when follicles of 0.53-1.00 mm but not 0.13-0.52 mm diameter were cultured for 48 h with LH + FSH under 70 kPa of a 50% O2, 45% N2 and 5% CO2 gas mixture, the proportions that synthesized high levels of progesterone (greater than or equal to 4.0 ng), androstenedione (greater than or equal to 3 ng), and oestradiol (greater than or equal to 0.8 ng) were significantly influenced by genotype (FF greater than F+ greater than or equal to ++; P less than 0.05 for each steroid). No significant genotypic differences were noted for testosterone synthesis. Collectively, these results show that the Booroola F-gene has an influence on the maturation of ovarian follicles from an early stage of growth.     

Relationship of macroscopic appearance of the surface of bovine ovarian follicles concentrations of steroids in follicular fluid, and maturation of oocytes in vitro

The relationship among opaqueness of the surface of bovine ovarian follicles, concentrations of follicular steroids, and capacity of oocytes to achieve nuclear maturation in vitro was examined in this study. Follicles greater than or equal to 5 mm in diameter were classified as clear (n=68) or opaque (n=72) based on their surface appearance. An oocyte and follicular fluid (FF) were removed from each follicle. Each oocyte was cultured, and the concentration of estradiol (E), progesterone (P), and testosterone (T) was determined for each sample of FF. Oocytes that extruded the first polar body by 30 h in culture were considered mature. All other oocytes were immature. More (p less than 0.05) mature oocytes came from clear (56%) than opaque follicles (29%). Clear follicles had lower concentrations of E (p less than 0.05) and P (p less than 0.10) in FF than opaque follicles. Follicles with mature oocytes had greater (p less than 0.05) concentrations of P than follicles with immature oocytes. Follicles were separated into three categories based on ratio of P:E in FF: high = P:E greater than or equal to 10, medium = P:E greater than or equal to 1 less than 10, and low = P:E less than 1. The percentage of mature oocytes from clear follicles was similar for high (64%), medium (48%), and low (57%) P:E groups; however, the percentage of mature oocytes from opaque follicles was greater (p less than 0.05) for the high (59%) than for the medium (21%) or low (19%) P:E groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flow cytometric analysis of head and neck carcinoma DNA index and S-fraction from paraffin-embedded sections: comparison with malignancy grading

Archival, paraffin-embedded, pathology specimens representing pretreatment tissue biopsies from 73 patients with epidermoid carcinoma of the head and neck were analyzed for DNA Index and %S-phase cells by flow cytometry and were scored for quantitative histomorphology. The DNA fluorescence/light scatter size patterns derived from paraffin-embedded specimens were shown to be essentially the same as those from mechanically disaggregated, ethanol-fixed cells obtained from the same tissue specimen. Patterns ranged from lymphocyte-like to highly abnormal DNA Index cytokinetic patterns. The DNA Index values ranged from 0.70 to 3.50 (median 1.42), with an aneuploidy frequency of 63/73 (86%). DNA distribution %S ranged from 4% to 45% (mean 19), with the microscopic malignancy grading showing broad heterogeneity (mean 2.1, range 1.0-3.0, where 1.0-1.7 = well differentiated, 1.8-2.3 = moderately differentiated, 2.4-3.0 = poorly differentiated). Cross-comparison of these data showed that (1) the tumor %S was dependent on DNA Index (higher %S at higher ploidy), (2) low to high malignancy tumors were randomly distributed between diploid/near diploid tumors and high-degree DNA abnormality tumors, and (3) proliferative activity values broadly overlapped between low to high malignancy scored tumors. However, those carcinomas characterized by high DNA Index (greater than or equal to 1.50) and high %S-phase fractions (greater than or equal to 20) had a five fold higher incidence of high-degree malignancy, invasive tumors than diploid/near diploid (%S less than or equal to 19) tumors.     

Embryonic development and incidence of aneuploidy in two rabbit strains of different fecundity

The correlation between strain fecundity and (i) development and (ii) rate of aneuploidy was studied in rabbit preimplantation embryos obtained from 2 strains of different fecundity. Embryos were investigated at Days 3-6 (preimplantation development) or Days 2, 4 and 6 post coitum (aneuploidy). Embryonic size and cell proliferation varied on the days of investigation, but with no consistent tendency in favour of one strain. The incidence of aneuploidy did not differ significantly between embryos from the 2 strains (P greater than 0.05). The multifactorially determined criterion of prolificacy was not selectively correlated with overall differences in embryonic preimplantation growth and rate of aneuploidy.     

Genetic alterations in gastric precancerous lesions

To investigate the occurrence of 17p (p53) loss of heterozygosity (LOH) and increased 4N or aneuploidy in gastric precancerous lesions (GPL), and their association with Helicobacter pylori (H pylori) infection. A total of 78 gastric mucosal biopsy specimens, including 10 normal mucosa and 68 gastric precancerous lesions [chronic atrophic gastritis (CAG, n = 20), intestinal metaplasia (IM, n = 12), low grade dysplasia (LGD, n = 15), and high grade dysplasia (HGD, n = 21)] were studied using PCR and flow cytometry. A modified Giemsa staining technique was used to detect H pylori. The study was performed in Erzurum Numune Hospital between 2007 and 2009. 17p (p53) LOH was observed in (1/20) 5% of CAG, in (2/12) 16% of IM, in (3/15) 20% of LGD and in (11/21) 53% of HGD. There was correlation between prevalence of 17p (p53) LOH and histological type of GPL (P = 0.004). Similarly, increased 4N or aneuploidy was detected in (1/20) 5% of CAG, in (1/12) 8% of IM, in (2/15) 13% of LGD and in (9/21) 43% of HGD. The correlation was found between aneuploidy and histological type of GPL (P = 0.009). However, there was no correlation between presence of H pylori infection in histological type of GPL (P = 0.921). On the other hand, a significant association was found between increased 4N or aneuploidy and 17p (p53) LOH in all of GPL (P = 0.0001). However, there was no statistically significant association between H pylori infection and 17p (p53) LOH or increased 4N/aneuplody in GPL. 17p (p53) LOH and increased 4N or aneuploidy are closely related to the early stages of gastric carcinogenesis.     

Effect of GnRH treatment during the anovulatory season on multiple ovulation rate and on follicular development during the ensuing pregnancy in mares

Seasonally anovulatory mares were injected, i.m., twice daily with a GnRH analogue (GnRH-A), and hCG was given when the largest follicle reached 35 mm in diameter. In Exp. 1, treatment was initiated on 23 December when the largest follicle per mare was less than or equal to 17 mm. An ovulatory response (ovulation within 21 days) occurred in 17 of 30 (57%) GnRH-A-treated mares on a mean of 15.8 days. The shortest interval to ovulation in control mares (N = 10) was 57 days. The diameter of the largest follicle first increased significantly 6 days after start of treatment. In Exp. 2, treatment was begun on 15 January and mares were categorized according to the largest follicle at start of treatment. The proportion of mares ovulating within 21 days increased significantly according to initial diameter of largest follicle (less than or equal to 15 mm, 9/25 mares ovulated; 15-19 mm, 13/21; 20-24 mm, 20/24; greater than 25 mm, 3/3). The multiple ovulation rate was greater (P less than 0.01) for treated mares (27/86 mares had multiple ovulations) than for control mares (2/35). Treated mares in which the largest follicle at start of treatment was greater than or equal to 25 mm had a higher (P less than 0.01) multiple ovulation rate (9/14) than did mares in which the largest follicle was less than 25 mm (18/72). The pregnancy rate for single ovulators was not different between control mares (26/30 pregnant mares) and treated mares (43/54).(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between concentrations of cortisol in ovarian follicular fluid and various biochemical markers of follicular differentiation in cyclic and anovulatory cattle

Concentrations of cortisol were determined in pooled fluid of small (less than 10 mm) and large (greater than or equal to 10 mm) follicles of cyclic cattle (Exp. 1), and in fluid of the largest follicle of 17 post-partum anovulatory cows (Exp. 2). In Exp. 1, concentrations of cortisol in small follicles were greater (P less than 0.05) than in large follicles (14.7 versus 13.2 ng/ml), and varied significantly with stages of the cycle; small and large follicles had the highest cortisol concentration during the early luteal phase of the cycle. Large follicles had 2-fold greater concentrations of oestradiol than did small follicles, whereas small follicles had 2-fold greater concentrations of androstenedione than did large follicles. Across pools of follicular fluid, cortisol concentrations were correlated only to androstenedione concentrations (r = 0.65, P = 0.07). In Exp. 2, concentrations of cortisol did not significantly differ between oestrogen-active (oestradiol greater than progesterone in follicular fluid) and oestrogen-inactive (progesterone greater than oestradiol) follicles, although oestrogen-active follicles had a 24-fold greater concentration of oestradiol than did oestrogen-inactive follicles. Cortisol concentrations were correlated to hCG binding capacity of thecal cells (r = -0.35, P = 0.08) and to follicular diameter (r = 0.45, P less than 0.05). These results suggest that normally fluctuating concentrations of cortisol in follicular fluid of cattle play little or no active role in follicular differentiation in vivo.     

Physiological and behavioral responses of gray wolves (Canis lupus) to immobilization with tiletamine and zolazepam

We conducted a series of experiments to examine the efficacy of Telazol (TEL) for immobilization of captive gray wolves (Canis lupus). Ten wolves were immobilized with either 5 or 10 mg/kg TEL. There was no difference in induction time (6.5 +/- 0.8 versus 5.8 +/- 1.2 min; P = 0.63) between the two doses, but the time to initial arousal was longer for the higher dose (P = 0.0008). Wolves were again immobilized with 10 mg/kg TEL and upon initial arousal were given additional doses of either 5.0 mg/kg TEL or 2.5 mg/kg ketamine (KET) to maintain immobilization. Wolves given boosters of TEL had longer second recovery times than wolves given KET (P = 0.01). There were no differences in induction times or arousal times for wolves immobilized with TEL that had been reconstituted with sterile water and stored at 20 C for 30 days (P greater than or equal to 0.11) or 60 days (P greater than or equal to 0.27) when compared to immobilization times using fresh solution. Induction times for wolves given TEL reconstituted with water and propylene glycol and stored for 60 days at -9 C were longer (P less than 0.05) than such times for wolves given standard TEL, but time to initial arousal was unchanged (P greater than or equal to 0.44). There were no differences in heart rates (P = 0.36), blood pressures (P = 0.32), respiratory rates (P = 0.91), and rectal temperatures (P = 0.62) between the two TEL doses. Telazol was shown to be an effective and safe immobilizing agent for gray wolves.     

The population mean predicts the number of deviant individuals.

OBJECTIVE--To examine the relation between the prevalence of deviation and the mean for the whole population in characteristics such as blood pressure and consumption of alcohol. DESIGN--Re-examination of standardised data from the Intersalt study, an international, multicentre study on the determinants of blood pressure. SETTING AND SUBJECTS--Samples of adults representing 52 populations in 32 countries. MAIN OUTCOME MEASURES--The relations, expressed as correlation coefficients, between the mean population values for blood pressure, body mass index, alcohol consumption, and sodium intake and the prevalence of, respectively, hypertension (greater than or equal to 140 mm Hg), obesity (body mass index greater than or equal to 30 kg/m2), high alcohol intake (greater than or equal to 300 ml/week), and high sodium intake (greater than or equal to 250 mmol/day). RESULTS--There were close and independent associations between the population mean and the prevalence of deviance for each of the variables examined: correlation coefficients were 0.85 for blood pressure, 0.94 for body mass index, 0.97 for alcohol intake, and 0.78 for sodium intake. CONCLUSIONS--These findings imply that distributions of health related characteristics move up and down as a whole: the frequency of "cases" can be understood only in the context of a population''s characteristics. The population thus carries a collective responsibility for its own health and well being, including that of its deviants.     

Changes in gonadotrophin secretion and ovarian antral follicular activity in seasonally breeding sheep throughout the year

Overall, significantly more antral follicles greater than or equal to 1 mm diameter were present in Romney ewes during anoestrus than in the breeding season (anoestrus, 35 +/- 3 (mean +/- s.e.m.) follicles per ewe, 23 sheep; Day 9-10 of oestrous cycle, 24 +/- 1 follicles per ewe, 22 sheep; P less than 0.01), although the mean numbers of preovulatory-sized follicles (greater than or equal to 5 mm diam.) were similar (anoestrus, 1.3 +/- 0.2 per ewe; oestrous cycle, 1.0 +/- 0.1 per ewe). The ability of ovarian follicles to synthesize oestradiol did not differ between anoestrus and the breeding season as assessed from the levels of extant aromatase enzyme activity in granulosa cells and steroid concentrations in follicular fluid. Although the mean plasma concentration of LH did not differ between anoestrus and the luteal phase of the breeding season, the pattern of LH secretion differed markedly; on Day 9-10 of the oestrous cycle there were significantly more (P less than 0.001) high-amplitude LH peaks (i.e. greater than or equal to 1 ng/ml) in plasma and significantly fewer (P less than 0.001) low amplitude peaks (less than 1 ng/ml) than in anoestrous ewes. Moreover, the mean concentrations of FSH and prolactin were significantly lower during the luteal phase of the cycle than during anoestrus (FSH, P less than 0.05, prolactin, P less than 0.001). It is concluded that, in Romney ewes, the levels of antral follicular activity change throughout the year in synchrony with the circannual patterns of prolactin and day-length. Also, these data support the notion that anovulation during seasonal anoestrus is due to a reduced frequency of high-amplitude LH discharges from the pituitary gland.     

Effects of lactational and reproductive status on ovarian follicular waves in llamas (Lama glama)

The effects of lactational status and reproductive status on patterns of follicle growth and regression were studied in 41 llamas. Animals were examined daily by transrectal ultrasonography for at least 30 days. The presence or absence of a corpus luteum and the diameter of the largest and second largest follicle in each ovary were recorded. Llamas were categorized as lactating (N = 16) or non-lactating (N = 25) and randomly allotted to the following groups (reproductive status): (1) unmated (anovulatory group, N = 14), (2) mated by a vasectomized male (ovulatory non-pregnant group, N = 12), (3) mated by an intact male and confirmed pregnant (pregnant group, N = 15). Ovulation occurred on the 2nd day after mating with a vasectomized or intact male in 26/27 (96%) ovulating llamas. Interval from mating to ovulation (2.0 +/- 0.1 days) and growth rate of the preovulatory follicle (0.8 +/- 0.2 mm/day) were not affected by lactational status or the type of mating (vasectomized vs intact male). Waves of follicular activity were indicated by periodic increases in the number of follicles detected and an associated emergence of a dominant follicle that grew to greater than or equal to 7 mm. There was an inverse relationship (r = -0.2; P = 0.002) between the number of follicles detected and the diameter of the largest follicle. Successive dominant follicles emerged at intervals of 19.8 +/- 0.7 days in unmated and vasectomy-mated llamas and 14.8 +/- 0.6 days in pregnant llamas (P = 0.001). Lactation was associated with an interwave interval that was shortened by 2.5 +/- 0.05 days averaged over all groups (P = 0.03). Maximum diameter of anovulatory dominant follicles ranged from 9 to 16 mm and was greater (P less than 0.05) for non-pregnant llamas (anovulatory group, 12.1 +/- 0.4 mm; ovulatory group, 11.5 +/- 0.2 mm) than for pregnant llamas (9.7 +/- 0.2 mm). In addition, lactation was associated with smaller (P less than 0.05) maximum diameter of dominant follicles averaged over all reproductive statuses (10.4 +/- 0.2 vs 11.7 +/- 0.3 mm). The corpus luteum was maintained for a mean of 10 days after ovulation in non-pregnant llamas and to the end of the observational period in pregnant llamas. The presence (ovulatory non-pregnant group) and persistence (pregnant group) of a corpus luteum was associated with a depression in the number of follicles detected and reduced prominence of dominant follicles (anovulatory group greater than ovulatory non-pregnant group greater than pregnant group).(ABSTRACT TRUNCATED AT 400 WORDS)     

Flow cytometric analysis of DNA aneuploidy in primary and metastatic human solid tumors

DNA histograms were measured by flow cytometry for 656 human solid tumors (365 primary and 291 metastatic). The proportion of aneuploid cells in cell suspensions obtained by mechanical disaggregation was significantly higher than those obtained after enzymatic disaggregation (collagenase + DNAse) of the same tumor. A strong correlation was observed between the values of DNA-indices measured after staining with propidium iodide and with 4',-6-diamidino-2-phenylindole (r = 0.97). Aneuploid cells were observed in 430 tumors (66%); 30 of these had two aneuploid stemlines, and two had three aneuploid stemlines. The overall frequency of aneuploidy was 61% among primary and 71% among metastatic tumors. The median value of the DNA index was 1.67 for 224 primary aneuploid tumors and 1.68 for 206 metastatic aneuploid tumors. For most diseases, the largest proportion of aneuploid primary and metastatic tumors had DNA-indices in the hypertriploid region. No major differences in frequency and degree of aneuploidy was observed between primary and metastatic tumors. For carcinomas of the bladder and prostate, frequency of aneuploidy was higher among poorly differentiated, than among moderately and well-differentiated tumors. For carcinomas of the breast and for sarcomas, tumors with DNA-indices of greater than 2.0 were observed mostly in the poorly differentiated group. For patients with carcinomas of the bladder and prostate most tumors at earlier stages of disease were diploid; whereas most tumors at later stages of disease were aneuploid. For patients with carcinomas of the ovary, colon, and kidney, no relationship between stage of disease and aneuploidy was evident.     

A comparison of histological and non-histological indices of atresia and follicular function

Histological indices of atresia for bovine follicles greater than or equal to 5 mm in diameter were compared with potential non-histological indices of atresia such as opaqueness of the exposed surface of non-excised follicles, concentrations of steroids in follicular fluid (FF) and specific binding of gonadotropins by granulosal cells. Each non-excised follicle was classified as clear (n=86), intermediate (n=79), or opaque (n=115), on the basis of the appearance of its exposed surface. A section of tissue from each follicle was evaluated histologically for atresia and assigned to one of the following categories: non-atretic, intermediately atretic, strongly atretic, or luteinized-atretic. Concentrations of estradiol (E), progesterone (P), and testosterone (T) and capacity of granulosal cells to bind radioactive ovine follicle-stimulating hormone (oFSH) and human chorionic gonadotropin (hCG) were determined for each follicle. Overall incidence of atresia was similar for clear (n=66%), intermediate (60%), and opaque (72%) follicles. Opaque follicles, however, were more likely to be strongly atretic (42%) than were clear (21%) or intermediate (23%) follicles. Non-atretic and intermediately atretic follicles had similar concentrations of E, P, and T and similar capacities to bind gonadotropins. Strongly atretic and luteinized-atretic follicles contained a higher concentration of P, lower E, and a reduced capacity of granulosal cells to bind oFSH than non-atretic and intermediately atretic follicles. A ratio of P:E in FF greater than or equal to 10 usually (greater than 90%) indicated that a follicle was atretic. However, lesser ratios of P:E did not accurately indicate whether follicles were atretic.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of flushing of blastocysts on days 10-13 on the life-span of the corpora lutea in the pig

Blastocysts were flushed out of both uterine horns of gilts on Days 10, 11, 12 or 13. In mated non-pregnant gilts flushing had no effect on progesterone profile or cycle length (20.8 +/- 0.4 versus 20.6 +/- 0.6 days in the preflush cycle, N = 6, mean +/- s.e.m.). Flushing the blastocysts out of the uterine horns on Day 10 resulted in a cycle with a normal progesterone profile and a normal length (21.2 +/- 0.4 days, N = 5). Flushing on Days 11, 12 or 13 resulted in a normal cycle or in maintenance of the CL for 3-13 days as indicated by elevated progesterone concentrations and an increased interoestrous interval of, respectively, 22.0 +/- 1.2 versus 19.8 +/- 0.6 days (Day 11; N = 6), 24.8 +/- 1.4 versus 21.0 +/- 0.6 days (Day 12; N = 5; P less than 0.05) and 26.3 +/- 2.3 versus 20.5 +/- 0.4 days (Day 13; N = 6; P less than 0.05). There was a positive relationship between the change in interoestrous interval and the interval between the first observed standing oestrus and flushing of the blastocysts (rs = 0.350; n = 22; P less than 0.1). There was a large variation in the diameter of the blastocysts flushed on the same day. Only in those gilts in which the blastocysts were greater than or equal to 8 mm or filamentous were the CL maintained for 3 or more days. These results indicate that a first signal for maternal recognition of pregnancy is generated on Day 12 and that blastocysts greater than or equal to 8 mm are required for prolongation of CL function for 3 or more days. Since CL function is only extended for a maximum of 13 days (mean 7.4 +/- 1.0), a second signal seems necessary to maintain the CL for the whole period of pregnancy.     

Decreased follicular steroids and insulin-like growth factor-I and increased atresia in diabetic gilts during follicular growth stimulated with PMSG

Four streptozotocin-diabetic gilts (maintained on exogenous insulin for 3 months) and 4 normoglycaemic gilts were treated with 600 i.u. PMSG. Diabetic gilts had insulin therapy removed at the time of PMSG administration. Plasma glucose averaged 463 +/- 5 mg/100 ml for diabetic gilts and 82 +/- 4 mg/100 ml for control gilts over the 72-h sampling period. Serum insulin was lower in diabetic than in normoglycaemic gilts (glycaemic state by time interaction; P less than 0.0001). At ovary removal 75 h after PMSG, numbers and percentages of large (greater than or equal to 7 mm) and medium (3-6 mm) non-atretic follicles were similar for diabetic and control gilts (31 vs 68%; s.e.m. = 7; P less than 0.05). Diabetic gilts had a greater percentage of atretic follicles over all size classes (50 vs 21%; s.e.m. = 7; P less than 0.03). After PMSG, LH was suppressed within 12 h in control gilts and remained similar to values in diabetic gilts until 72 h, when LH was elevated in 2 diabetic gilts (glycaemic state by time interaction; P less than 0.001). Pulsatile LH patterns during 52-55 h after PMSG were not affected by glycaemic state. Serum concentrations of IGF-I tended (P less than 0.1) to be lower in diabetic gilts. Concentrations of oestradiol and FSH in serum were similar in diabetic and control gilts. Follicular fluid concentrations of oestradiol in follicles greater than or equal to 7 mm were lower in diabetic than normoglycaemic gilts (341 vs 873 ng/ml; s.e.m. = 86; P less than 0.05). Testosterone was higher in follicles 3-6 mm in diameter in diabetic than in normoglycaemic gilts (142 vs 80 ng/ml; s.e.m. = 26; P less than 0.05). Progesterone concentrations in follicular fluid were not affected by glycaemic state. Concentrations of IGF-I in follicles greater than or equal to 7 mm were lower in diabetic than control gilts (150 vs 200 ng/ml; s.e.m. = 13; P less than 0.05). We conclude that follicles of diabetic gilts respond to external gonadotrophic stimulation with decreased hormone production and increased ovarian follicular atresia, despite an absence of effects on circulating gonadotrophin and oestradiol concentrations.     

胸腔积液中肺腺癌细胞EGFR突变状态与DNA含量的相关性

摘要 目的：探究胸腔积液中肺腺癌细胞表皮生长因子受体（epidermalgrowthfactorreceptor,EGFR）突变状态与DNA含量的相关性,以期探究EGFR突变状态是否同肿瘤的恶性程度存在一定关联。方法：选择2015年1月至2020年1月于我院接受EGFR基因检测以及基因定量分析的591例肺腺癌患者为研究对象,按照其是否出现EGFR基因突变将其分为突变组（335例）与非突变组（256例）,两组患者的胸腔积液均使用激光图像细胞仪开展DNA含量以及非整倍体峰检测,并开展组间差异性比较。结果：（1）将591例患者按照年龄、性别及是否吸烟等临床特征进行分组对比显示,性别（P=0.034）与吸烟（P=0.007）同肺腺癌患者胸腔积液细胞出现EGFR突变具有一定关联,而年龄因素与是否出现突变无明显相关性（P>0.05）;（2）突变组患者的最大DNA指数（DI）、大于5C细胞的平均DI以及大于9C细胞的平均DI均明显高于非突变组,组间差异明显（P<0.05）;（3）开展DNA非整倍体细胞峰比较显示突变组在单峰、双峰占比中明显高于非突变组,而无峰占比明显低于非突变组（P<0.05）,多峰占比方面两组差异不大（P>0.05）。结论：经研究显示,同未出现EGFR突变的肺腺癌患者相比较,发生EGFR突变的肺腺癌患者明显DI值更高,非整倍体细胞以及非整倍体峰值也呈现异常升高态,这提示EGFR发生突变的肺腺癌患者恶变洗吧的侵袭性更强。     

Cell death mechanisms associated with G2 radiosensitivity in patients with prostate cancer and benign prostatic hyperplasia

Cells respond to genotoxic insults such as ionizing radiation by halting in the G2 phase of the cell cycle. Delayed cell death (mitotic death) can occur when the cell is released from G2, and specific spindle defects form endopolyploid cells (endoreduplication/tetraploidy). Enhanced G2 chromosomal radiosensitivity has been observed in many cancers and genomic instability syndromes, and it is manifested by radiation-induced chromatid aberrations observed in lymphocytes of patients. Here we compare the G2 chromosomal radiosensitivity in prostate patients with benign prostatic hyperplasia (BPH) or prostate cancer with disease-free controls. We also investigated whether there is a correlation between G2 chromosomal radiosensitivity and aneuploidy (tetraploidy and endoreduplication), which are indicative of mitotic cell death. The G2 assay was carried out on all human blood samples. Metaphase analysis was conducted on the harvested chromosomes by counting the number of aberrations and the mitotic errors (endoreduplication/tetraploidy) separately per 100 metaphases. A total of 1/14 of the controls were radiosensitive in G2 compared to 6/15 of the BPH patients and 15/17 of the prostate cancer patients. Radiation-induced mitotic inhibition was assessed to determine the efficacy of G2 checkpoint control in the prostate patients. There was no significant correlation of G2 radiosensitivity scores and mitotic inhibition in BPH patients (P = 0.057), in contrast to prostate cancer patients, who showed a small but significant positive correlation (P = 0.029). Furthermore, there was no significant correlation between G2 radiosensitivity scores of BPH patients and endoreduplication/ tetraploidy (P = 0.136), which contrasted with an extremely significant correlation observed in prostate cancer patients (P < 0.0001). In conclusion, cells from prostate cancer patients show increased sensitivity to the induction of G2 aberrations from ionizing radiation exposure but paradoxically show reduced mitotic indices and aneuploidy as a function of aberration frequency.     

Follicular dynamics and dominance in Booroola x Finnish Landrace and Booroola x Suffolk ewes heterozygous for the F gene

To study the influence of the F gene on follicular dynamics and dominance, 2-year-old Booroola x Finnish Landrace (BFL, N = 17) and Booroola x Suffolk (BS, N = 18) ewes were compared with contemporary purebred Finn (FL, N = 18) and Suffolk (S, N = 18) ewes. In Exp. 1, oestrous cycles of ewes were synchronized during the breeding season with progestagen-impregnated sponges. At sponge removal (Day 0), 14 days after insertion, ewes of each of the 4 genetic groups were assigned to Group 1 in which all follicles visible on both ovaries were destroyed by electrocauterization except for the largest (F1) which was marked, Group 2 in which all visible follicles on both ovaries were destroyed, or Group 3 in which the 3 largest follicles of both ovaries were identified as F1, F2 and F3 and marked. At 48 h after treatment (Day 2), follicular growth was evaluated. At Day 0, the mean number of small follicles (1-3 mm) was higher (P less than 0.05) for BS, S and BFL (35.8, 35.1 and 32.9) than FL (24.9) ewes. Large follicles (greater than or equal to 4 mm) were more numerous (P less than 0.05) in FL (3.5) than in BS (2.1) ewes, BFL and S ewes being intermediate. Diameter of the F1 follicle was larger (P less than 0.05) for S (7.6 mm) than FL, BS and BFL (5.8, 5.1 and 5.1 mm) ewes. In Group 1, all F1 follicles marked at Day 0 ovulated at oestrus after sponge removal for BFL, BS and S ewes while in FL ewes, 2 of 6 F1 follicles regressed. In ewes ovulating, only the F1 follicle ovulated except for one S ewe which shed one more ovum. In Group 2, there were no follicles greater than or equal to 4 mm at Day 2 and no ewes ovulated after treatment. In Group 3, the proportion of marked follicles that ovulated was higher for S ewes than in those of the prolific genotypes. The number of follicles not marked at Day 0 but ovulating (compared to the total number of ovulations) was higher in BFL, BS and FL (8/11, 9/13 and 9/13) than S (3/10) ewes. In Exp. 2, prolific (BFL + BS) and non-prolific (S) ewes were compared following destruction of follicles greater than or equal to 3 mm with the F1 left intact (Treatment 1) or destroyed (Treatment 2), 12 days after sponge insertion.(ABSTRACT TRUNCATED AT 400 WORDS)