Further studies on the histological,cytological and cytogenetic effects of nogalamycin in mammals

The histological, cytological and cytogenetic effects of nogalamycin were studied in rats, mice and cultured human leukocytes. Four standard test systems were used in the cytological studies: (1) analysis of spermatogonial cells, (2) cytological evaluation of bone marrow metaphase plates, (3) micronucleus test in polychromatic erythrocytes, and (4) determination of chromosomal aberrations in cultured human leukocytes. The results of the studies indicated that the types and frequencies of cytological errors induced by the drug were not significantly different from the concurrent control.The reduced incidence of fertile matings from 22 to 35 days after treatment is attributed to the cytostatic effect of nogalamycin (NM) on spermatogonia and spermatocytes. Subsidence of NM-induced inhibition of spermatogonium differentiation and spermatocyte maturation occured 37 days post-treatment. Accordingly, fertile matings, which had reached a zero level by the 23rd day, occurred 35 days after treatment, and reached the control level between 47 and 49 days post-treatment.     

Del (10)p autosomal deletion syndrome: clinical, cytogenetic and gene marker studies.

A 46,XX,del(10)p13 karyotype (Paris Conference, 1971) was identified in a 5-year-old Negro girl with mental and growth retardation, brachy- and trigonocephaly, downward slanting palpebral fissures, hypotelorism, epicanthal folds, ptosis, strabismus, dysplastic nose, high-arched palate, microdontia, small low-set posteriorly rotated ears, asymmetrical thorax, wide-spaced nipples, and minor abnormalities of hands and feet. Both parents and a brother had normal karyotypes. Expression of more than 50 polymorphic gene loci determining blood groups, serum proteins and red cell enzymes was studied. The results did not permit localization of a gene locus on the deleted segment of chromosome 10. The proposita was heterozygous for the Rh and MN blood groups and for the red cell enzymes adenosine deaminase, glutamate pyruvate transaminase and esterase D. These gene loci are thereby excluded from region 10p13 yields 10pter.     

Isodicentric Y chromosome: cytogenetic,molecular and clinical studies and review of the literature

Dicentrics are among the most common structural abnormalities of the human Y chromosome. Predicting the phenotypic consequences of different duplications and deletions of dicentric Y chromosomes is usually complicated by varying degrees of mosaicism (45,X cell lines), which may, in some cases, remain undetected. Molecular studies in patients with dicentric Y chromosomes have been few, and only two studies have attempted to determine the presence of SRY (the putative testis-determining factor gene). We report an 18-year-old female with short stature, amenorrhea, hirsutism, hypoplastic labia minora, and clitoromegaly who has a 45,X/46,X,idic(Y)(p11.32)/47,X,idic(Y)(p11.32),idic(Y) (p11.32) karyotype. Southern analysis using Y-specific probes (Y97, 2D6, 1F5, pY3.4) and polymerase chain reaction (PCR) analysis using primers for ZFY and SRY were positive for all loci tested, indicating that almost all of the Y chromosome was present. Our findings and an extensive review of the literature emphasize the importance of molecular analyses of abnormal Y chromosomes before any general conclusions can be reached concerning the relative effects of the Y-chromosome abnormality and mosaicism on sexual differentiation.     

Partial trisomy 9 : clinical and cytogenetic correlations.

A study of three new cases with different trisomies involving chromosome 9 and a review of about 100 cases of partial trisomy 9 reported in the literature, suggested some cytogenetical and clinical correlations and lead us to propose the nomenclature of Rethore's syndrome type 1 and type 2.     

Familial systemic lupus erythematosus: a comparison of clinical manifestations and antibody presentation in three ethnic groups.

The serologic and clinical features of patients from pedigrees multiplex for systemic lupus erythematosus (SLE) were evaluated among three ethnic groups: Hispanics, African-Americans and European-Americans. Data were obtained from a registry of 123 pedigrees, composed of 4 Hispanic, 40 African-American and 79 European-American pedigrees. All patients met at least four criteria for the diagnosis of SLE per the American College of Rheumatology. Clinical information was obtained through review of the medical records and questionnaires completed by the participants. Ethnicity by self-identification was found to be an important factor influencing the prevalence of serologic results and clinical features. Anti-nRNP occurred more frequently in African-Americans (45.7%) than in European-Americans (7.5%) or Hispanics (0%) (p<0.0000001), as did anti-Sm (18.5% vs 1.6% and 0%, respectively) (p<0.000001). Malar rash, photosensitivity and oral ulcers were most frequent in the Hispanic population while proteinuria and leukopenia predominated in the African-American population. Arthritis and lymphopenia were present in a similar proportion in all ethnic groups. These results show that many of the ethnic differences known for isolated cases of SLE are also present in familial cases of SLE.     

46,XX/46,XX,r (2)(p25q37) mosaicism: clinical and cytogenetic studies.

A severely mentally retarded and physically handicapped girl is described who has 46,XX/46,XX,r(2)(p25q37) mosaicism. This is the first ring 2 chromosome to be described in Man. Studies of the behaviour of the ring showed that it was stable in diploid cells which had increased in frequency over a period of seven years, but unstable in tetraploid cells which were at a much higher frequency than in normal individuals. It is concluded that in some cases the phenotypic consequences of ring chromosome formation may be due more to their disturbing the regulation of cell division than to the loss of genetic material. Current models of ring chromosome behaviour do not account for the induction of tetraploidy.     

Familial hyperlysinemia: enzyme studies, diagnostic methods, comments on terminology.

Enzyme assays of skin fibroblasts from five children with familial hyperlysinemia from unrelated families are added to the previous report of three children from two unrelated families. In all instances there was a deficiency in lysine-ketoglutarate reductase, saccharopine dehydrogenase, and saccharopine oxidoreductase activities. To complete the studies on the enzymes associated with familial hyperlysinemia, saccharopine oxidoreductase was partially purified from human liver and characterized. The activity did not separate from that of lysine-ketoglutarate reductase or saccharopine dehydrogenase. A simple screening test for familial hyperlysinemia is described based on the evolution of 14CO2 from lysine-14C by skin fibroblasts. The test differentiated, without overlap, seven patients with familial hyperlysinemia from control subjects. The relation of the two genetic entities involving lysine degradation, familial hyperlysinemia and saccharopinuria, is discussed. It is suggested that familial hyperlysinemia, type I, be applied to patients with major defects in lysine-ketoglutarate reductase and saccharopine dehydrogenase, and that familial hyperlysinemia, type II, to be used to designate patients in whom significant amounts of lysine-ketoglutarate reductase are retained. The nomenclature would be consistent with that of an analogous disease, orotic aciduria.     

Molecular, cytogenetic, and clinical investigations of Prader-Willi syndrome patients.

Thirty-seven patients presenting features of the Prader-Willi syndrome (PWS) have been examined using cytogenetic and molecular techniques. Clinical evaluation showed that 29 of these patients fulfilled diagnostic criteria for PWS. A deletion of the 15q11.2-q12 region could be identified molecularly in 21 of these cases, including several cases where the cytogenetics results were inconclusive. One clinically typical patient is deleted at only two of five loci normally included in a PWS deletion. A patient carrying a de novo 13;X translocation was not deleted for the molecular markers tested but was clinically considered to be "atypical" PWS. In addition, five cases of maternal heterodisomy and two of isodisomy for 15q11-q13 were observed. All of the eight patients who did not fulfill clinical diagnosis of PWS showed normal maternal and paternal inheritance of chromosome 15 markers; however, one of these carried a ring-15 chromosome. A comparison of clinical features between deletion patients and disomy patients shows no significant differences between the two groups. The parental ages at birth of disomic patients were significantly higher than those for deletion patients. As all typical PWS cases showed either a deletion or disomy of 15q11.2-q12, molecular examination should provide a reliable diagnostic tool. As the disomy patients do not show either any additional or more severe features than typical deletion patients do, it is likely that there is only one imprinted region on chromosome 15 (within 15q11.2-q12).     

Familial resemblance for anthropometric traits in dizygotic twins and siblings

Familial resemblance for fifty anthropometric traits was studied on a sample of 45 MZ, 101 DZ twin pairs and their 125 singleton siblings. Intraclass correlation coefficients were significant for all the traits. However, resemblance within DZ twin pairs was significantly greater than within sibs for 22 variables, showing that the former had a more correlated environment than the latter. The study also showed that head and facial traits were relatively more stable to the environmental factors than the body traits and hence more suitable for cross-cultural comparisons. The study listed measures of girth and skinfold, thickness as the most labile traits.     

Morphologic and hormonal correlates of true hermaphroditism in the rabbit

A macro-microscopical and histological investigation of the urogenital system organs of a rabbit-hermophrodite has been performed with an aim to compare the content of sex steroids in the peripheral and in the gonadal blood estimated by means of radioimmunological methods. Certain anomalies have been found out in the development of external and internal sex organs, kidneys and urinary bladder. Testosterone and estradiol concentration in blood flowing from the ovotestis is decreased, as it is in the periphral blood. The rabbit urogenital system organs have been studied from the 12th day of the intrauterine development up to the 10th day of the postnatal life. The results of the investigation performed make it possible to consider that the developmental anomalies in the rabbit-hermophrodite have, evidently, appeared between the 20th--25th days of its intrauterine development as a result of certain disbalance of sex steroids.     

Myelomonocytic leukemia: clinical, cytological, and cytogenetic studies of acute, subacute, and chronic forms (author's transl)]

44 patients suffering from myelomonocytic leukemia (MML) have been observed over the last four years. They have been subclassified in acute myelomonocytic and acute monoblastic leukemias (AMML, n = 12; AMoL, n = 10), subacute myelomonocytic leukemias (SMML, n = 13), and chronic myelomonocytic leukemias (CMML, n = 9) on the basis of bone marrow cytology(blast and promonocyte counts, maturation of granulopoesis) and cytochemical findings (peroxydase and unspecific esterase reaction). This subclassification has been proved to be of prognostic relevance by its good correlation with the mean survival times (AMML : 4.5 months, AMoL : 2.4 months, SMML : 8 months, CMML : 18 months). The acute forms have been treated in general with combined cytostatic chemotherapy, whereas SMML and CMML have been treated this way only in case of progression to an acute phase. These progressions to an AMML have been observed more often and earlier in subacute forms than in chronic forms. The diagnosis of SMML and CMML is supported by the finding of sea-blue histiocytes in the bone marrow, increased lysozyme levels in serum and urine and by the absence of the Philadelphia-Chromosome.     

Segregation of FRAXE in a large family: clinical, psychometric, cytogenetic, and molecular data.

During an ongoing study on X-linked mental retardation, we ascertained a large family in which mild mental retardation was cosegregating with a fragile site at Xq27-28. Clinical, psychometric, cytogenetic, and molecular studies were performed. Apart from mild mental retardation, affected males and females did not show a specific clinical phenotype. Psychometric assessment of four representative affected individuals revealed low academic achievements, with verbal and performance IQs of 61-75 and 70-82, respectively. Cytogenetically the fragile site was always present in affected males and was not always present in affected females. With FISH the fragile site was located within the FRAXE region. The expanded GCC repeat of FRAXE was seen in affected males and females either as a discrete band or as a broad smear. No expansion was seen in unaffected males, whereas three unaffected females did have an enlarged GCC repeat. Maternal transmission of FRAXE may lead to expansion or contraction of the GCC repeat length, whereas in all cases of paternal transmission contraction was seen. In striking contrast to the situation in fragile X syndrome, affected males may have affected daughters. In addition, there appears to be no premutation of the FRAXE GCC repeat, since in the family studied here all males lacking the normal allele were found to be affected.     

Comparison of gas and liquid ventilation: clinical, physiological, and histological correlates.

To differentiate the effects of gas and liquid ventilation on cardiopulmonary function during early development, we compared the clinical, physiological, and histological profiles of gas- and liquid-ventilated preterm lambs (n = 16; 108-116 days gestation). Immediately after cesarean section delivery, ventilation commenced using gas delivered by a volume ventilator (n = 9) or liquid perfluorochemical (n = 7) delivered by a mechanically assisted liquid ventilation system. Pulmonary gas exchange, acid-base status, vital signs, and respiratory compliance were assessed during the 3-h protocol; sections of the lungs were obtained for histological analyses when the animals were killed. Six of nine gas-ventilated lambs expired from respiratory failure before 3 h, with the remaining animals experiencing severe respiratory insufficiency, pneumothoraces, and cardiovascular deterioration. Six of seven liquid-ventilated lambs survived with good gas exchange and cardiovascular stability and without fluorothorax; one experienced ventricular fibrillation before 1 h and expired despite pulmonary stability. Respiratory compliance was significantly greater in the liquid- than in the gas-ventilated lambs. Histological analyses of gas-ventilated lungs demonstrated nonhomogeneous lung expansion, with thick-walled gas exchange spaces containing proteinaceous exudate, hemorrhage, and hyaline membranes. In contrast, liquid-ventilated lungs appeared clear, with thin-walled and uniformly expanded gas exchange spaces that were free of hyaline membranes and luminal debris. Morphometric analyses demonstrated that surface area and gas exchange index were greater in the liquid- than in the gas-ventilated lambs. These results indicate that elimination of surface active forces by liquid ventilation during early development provides more effective gas exchange with less barotrauma compared with gas ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

X trisomy in an infertile bitch: cytogenetic, anatomic, and histologic studies

Three copies of the X chromosome were identified in a 5-year-old mixed breed infertile bitch. One year after the cytogenetic examination, the bitch died due to gastritis hemorrhagica, an inflammation of the mucus coat of the stomach. Dental studies showed congenital lack of some premolar and molar teeth. Ovaries were of normal shape and size. Also, histologic sections of the ovaries revealed their normal structure, with two corpora lutea and primary follicles. Phenotypic effects of X trisomy are discussed.     

Chorionic villi sampling: cytogenetic and clinical findings in 500 pregnancies.

The cytogenetic findings were analysed in a series of 500 pregnancies in which chorionic villi sampling was performed. In all cases a direct method was used, karyotyping being successful in 481 cases (96.2%). The main indication for sampling was maternal age over 36 (412 cases; 82.4%). Abnormal laboratory findings resulted in 24 terminations of pregnancy (4.8%); in addition five unexpected balanced chromosome rearrangements were detected. Twelve of 15 cytogenetic discrepancies were detected at amniocentesis, two after termination, and one at spontaneous abortion. Complete follow up data were available for the first 250 patients, among whom nine pregnancies (3.6%) ended in spontaneous abortion before the 20th week. There were no false negative findings. Seventy additional chromosome studies were performed because of failure of chorionic villi sampling or equivocal results, or for confirmation. Counselling before chorionic villi sampling should include the possibility that subsequent amniocentesis may be needed should mosaicism or other unexpected abnormalities be found. The success rate and accuracy of karyotyping chorionic villi samples by the direct method are acceptable but distinctly less than those of karyotyping cultured amniotic fluid cells.