Intratumoral variations in DNA ploidy and s-phase fraction in human breast cancer.

To study intratumoral DNA ploidy heterogeneity and S-phase fraction (SPF) variability, we prospectively collected five different samples from 48 breast carcinomas and each sample was analysed separately by flow cytometry. Aneuploidy rate was 89.6% after analysis of four or five samples. DNA ploidy heterogeneity, i.e., different samples classified as either DNA euploid or DNA aneuploid in the same tumor was seen in 17%, and DNA index heterogeneity, i.e., tumor populations with different DNA indices (DIs) seen in different samples was 44%. A statistical model defining SPF heterogeneity is proposed. SPF heterogeneity as defined by us was 71%, and as expected the SPF heterogeneity rate increased significantly with increasing number of analysed samples. Four or more samples are needed to detect the most deviant (highest) SPF values. An unrecognized intratumor heterogeneity of DNA ploidy and SPF may partly explain the conflicting results reported in the literature on the above prognostic indicators.     

Location-dependent variations in the material properties of the anterior cruciate ligament.

Our recent anterior drawer studies in human cadaveric knees [Guan and Butler, Adv. Bioengng 17, 5 (1990); Guan et al., Trans. orthop. Res. Soc. 16, 589 (1991)] have suggested that anterior bundles of the anterior cruciate ligament (ACL) develop higher load-related material properties than posterior bundles. This was confirmed when we reevaluated the axial failure data for these bundle-bone specimens from an earlier study [Butler et al., J. Biomechanics 19, 425-432 (1986)]. The purpose of this study was to determine, in a larger data set, if anteromedial and anterolateral bundles of the anterior cruciate ligament exhibit significantly larger load-related material properties than the posterior ligament bundles. Seven ACL-bone units from seven donors (the three tissues from the original study plus four new ones) were subdivided into three subunits, preserving the bone insertions. The subunits were failed in tension at a constant strain rate (100% s-1) and four material properties were compared within and between donors. The anterior bundles developed significantly larger moduli, maximum stresses, and strain energy densities to maximum stress than the posterior subunits. Moduli for the anterior vs posterior subunits averaged 284 MPa vs 155 MPa, maximum stresses averaged 38 MPa vs 15 MPa, and strain energy densities averaged 2.7 N m cc-1 vs 1.1 N m cc-1, respectively. No significant differences were found, however, among strains to maximum stress or between any of the other properties for the two anterior subunits. These results are important to the design of ligament replacements and suggest new experiments designed to distinguish in vivo force levels in these ACL bands, a possible reason for the material differences.     

Climate associated variations in the human serum albumin level.

Quantitative determinations of the human serum albumin level showed significantly higher values in tropical (Negroes 46.98 mg/ml, Indians 54.30 mg/ml) than in non-tropical populations (Germans 44.41 mg/ml). These observations are in agreement with those of several other authors. It is assumed that these variations in the serum albumin level are related to climate, and that they may indicate some biological advantage of higher albumin levels under the climatic conditions of tropical biotops. This hypothesis is discussed considering several aspects.     

Some biochemical properties of human breast tumor sialyltransferase

Sialyltransferase activity in normal human breast tissue and tumors was investigated with lactose, desialylated fetuin, and bovine submaxillary mucin as the acceptors. While microsomal preparations from the normal tissue showed little or no sialyltransferase activity toward these acceptors, tumors showed elevated enzymic activities. Tween-20 at 0.5% concentrations stimulated sialic acid transfer to all three acceptors. Another nonionic detergent, Triton X-100, stimulated asialo fetuin sialyltransferase activity while inhibiting activity toward asialo BSM and lactose. Interestingly, lysolecithin, a normal cellular constituent which possesses detergent properties also had an effect similar to that of Triton X-100. Thermal denaturation curves of enzymic activity toward asialo BSM, however, resembled those seen with asialo fetuin as the acceptor. Kinetic studies showed that at acceptor concentrations of 500 micrograms each, sialyl transfers to asialo fetuin, asialo BSM, and lactose showed apparent Km values of 50, 60, and 300 microM, respectively. At CMP-sialic acid concentrations of 300 microM, the Km values for the above acceptors were 25, 15, and 5000 microM.     

Variability in the properties of silicone gel breast implants.

Several generations of silicone gel breast implants have been produced by implant manufacturers. The primary material usually viewed as the base material in the manufacture of implants is polydimethylsiloxane. Polymeric reactions are notorious for their variability and nonuniformity. The elastomer used in different types of implants can have vastly different properties. Furthermore, the material properties associated with a particular type of implant can vary considerably from one lot to the next. Considering the various designs, styles, and manufacturing techniques associated with silicone gel implants, knowledge of the original properties of the implants before implantation is important in determining the effects of aging in vivo. This study was conducted to investigate differences in key mechanical and chemical properties of silicone gel breast implant materials. The two types of implants chosen for analysis were Silastic I and Silastic II control implants. Material property data were determined for both types of controls and significant differences were found in their values. Lot-to-lot variability was also investigated and found to be significant.     

Tissue temperature profile in the human forearm during thermal stress at thermal stability.

The purpose of the present study was to investigate the effect of a range of water temperatures (Tw from 15 to 36 degrees C) on the tissue temperature profile of the resting human forearm at thermal stability. Tissue temperature (Tti) was continuously monitored by a calibrated multicouple probe during 3 h of immersion of the forearm. The probe was implanted approximately 9 cm distal from the olecranon process along the ulnar ridge. Tti was measured every 5 mm, from the longitudinal axis of the forearm (determined from computed tomography scanning) to the skin surface. Along with Tti, skin temperature (Tsk), rectal temperature (Tre), and blood flow were measured during the immersions. For all temperature conditions, the temperature profile inside the limb was linear as a function of the radial distance from the forearm axis (P less than 0.001). Temperature gradient measured in the forearm ranged from 0.2 +/- 0.1 degrees C C cm (Tw = 36 degrees C) to 2.3 +/- 0.5 degrees C cm (Tw = 15 degrees C). The maximal Tti was measured in all cases at the longitudinal axis of the forearm and was in all experimental conditions lower than Tre. On immersion at Tw less than 36 degrees C, the whole forearm can be considered to be part of the shell of the body. With these experimental data, mathematical equations were developed to predict, with an accuracy of at least 0.6 degrees C, the Tti at any depth inside the forearm at steady state during thermal stress.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of human breast development on the growth properties of primary cultures

Summary In experimental animal models the susceptibility of the mammary gland to neoplastic transformation is related to its degree of development and proliferative activity; this observation led us to determine whether the human breast epithelium also exhibits development-related differences, and whether these differences could be detected in an in vitro system. Normal breast tissue obtained from reduction mammoplasties of 9 patients ranging in age from 18 to 56 years were characterized in both whole mount preparations and organoids obtained after collagenase-hyaluronidase digestion by their degree of development based upon the types of lobules present. Lobules were classified into type 1 (Lob 1), composed of approximately 11 alveolar buds, the less developed; lobules type 2 (Lob 2), of moderate development, composed of approximately 47 ductules each, and lobules type 3 (Lob 3), composed of 80 ductules each, represented the highest level of development. Epithelial organoids obtained after digestion were plated in DMEM:F12 medium supplemented with hydrocortisone, cholera toxin, insulin and 5% horse serum with a calcium concentration of 1.05 mM Ca⁺⁺. Following attachment, the medium was replaced by medium containing 0.040 mM Ca⁺⁺. The percentage of attachment of organoids to the flask was greater in cells from Lob 1 (89–99%) and Lob 1+2 (79–100%) than in cells from Lob 3, which had a 53–67% attachment. The total yield of cells after 7 weeks in culture was also greater in cells derived from Lob 1 and Lob 1+2 than in cells from Lob 3. The total yield of cells obtained from primary cultures was not related to the number of organoids plated, but to the degree of development of the gland. The DNA-labeling index (DNA-LI) in intact breast tissue correlated with that in primary cultures; it was greater in Lob 1 and Lob 1+2 than in Lob 3. By flow cytometry, the highest percentage of cells in S-phase was seen in cells with the highest DNA-LI. We concluded that the growth characteristics of mammary epithelial cells in vitro in a low Ca⁺⁺ medium is modulated by the degree of development and differentiation of the gland. Supported by PHS Grant CA-38921 awarded by the National Cancer Institute, DHHS, and an Institutional Grant from the United Foundation of Greater Detroit.     

Site-dependent and subject-related variations in perioral thermal sensitivity

The Marstock method of limits was used to obtain thresholds for detection of cooling, warming, cold pain and heat pain for 34 young adults, upon eight spatially matched sites on the left and right sides of the face, the right ventral forearm and the scalp. Male and female subjects were tested by both a male and a female experimenter. Neither the experimenter nor the gender of the subject individually influenced the thresholds. The thermal thresholds varied greatly across facial sites: sixfold and tenfold for cool and warmth, respectively, from the most sensitive sites on the vermilion to the least sensitive facial site, the preauricular skin. Warm thresholds were 68% higher than cool thresholds, on average, and 12% higher on the left compared to the right side of the face. The mean cold pain threshold increased from 21.0°C on the hairy upper lip to 17.8°C on the preauricular skin. Sites on the upper lip were also most sensitive to noxious heat with pain thresholds of 42–43°C. The scalp was notably insensitive to innocuous and noxious changes in temperature. For the sensations of nonpainful cool and warmth, the more sensitive a site, the less the estimates of the thresholds differed between subjects. In contrast, for heat pain, the more sensitive a site, the more the estimates differed between subjects. Subjects who were relatively more sensitive to cool tended to be relatively more sensitive to warmth. Subjects’ sensitivities to nonpainful cool and warmth were less predictive of their sensitivities to painful cold and heat, respectively. Short-term within-subject variability increased with the magnitude of the thresholds. The lower the threshold, the more similar were repeated measurements of it, within a 5–25?s period.     

Site-dependent and subject-related variations in perioral thermal sensitivity

The Marstock method of limits was used to obtain thresholds for detection of cooling, warming, cold pain and heat pain for 34 young adults, upon eight spatially matched sites on the left and right sides of the face, the right ventral forearm and the scalp. Male and female subjects were tested by both a male and a female experimenter. Neither the experimenter nor the gender of the subject individually influenced the thresholds. The thermal thresholds varied greatly across facial sites: sixfold and tenfold for cool and warmth, respectively, from the most sensitive sites on the vermilion to the least sensitive facial site, the preauricular skin. Warm thresholds were 68% higher than cool thresholds, on average, and 12% higher on the left compared to the right side of the face. The mean cold pain threshold increased from 21.0 degrees C on the hairy upper lip to 17.8 degrees C on the preauricular skin. Sites on the upper lip were also most sensitive to noxious heat with pain thresholds of 42-43 degrees C. The scalp was notably insensitive to innocuous and noxious changes in temperature. For the sensations of nonpainful cool and warmth, the more sensitive a site, the less the estimates of the thresholds differed between subjects. In contrast, for heat pain, the more sensitive a site, the more the estimates differed between subjects. Subjects who were relatively more sensitive to cool tended to be relatively more sensitive to warmth. Subjects' sensitivities to nonpainful cool and warmth were less predictive of their sensitivities to painful cold and heat, respectively. Short-term within-subject variability increased with the magnitude of the thresholds. The lower the threshold, the more similar were repeated measurements of it, within a 5-25 s period.     

Effect of amino acid variations in the central region of human serum amyloid A on the amyloidogenic properties

Human serum amyloid A (SAA) is a precursor protein of the amyloid fibrils that are responsible for AA amyloidosis. Of the four human SAA genotypes, SAA1 is most commonly associated with AA amyloidosis. Furthermore, SAA1 has three major isoforms (SAA1.1, 1.3, and 1.5) that differ by single amino acid variations at two sites in their 104-amino acid sequences. In the present study, we examined the effect of amino acid variations in human SAA1 isoforms on the amyloidogenic properties. All SAA1 isoforms adopted α-helix structures at 4 °C, but were unstructured at 37 °C. Heparin-induced amyloid fibril formation of SAA1 was observed at 37 °C, as evidenced by the increased thioflavin T (ThT) fluorescence and β-sheet structure formation. Despite a comparable increase in ThT fluorescence, SAA1 molecules retained their α-helix structures at 4 °C. At both temperatures, no essential differences in ThT fluorescence and secondary structures were observed among the SAA1 isoforms. However, the fibril morphologies appeared to differ; SAA1.1 formed long and curly fibrils, whereas SAA1.3 formed thin and straight fibrils. The peptides corresponding to the central regions of the SAA1 isoforms containing amino acid variations showed distinct amyloidogenicities, reflecting their direct effects on amyloid fibril formation. These findings may provide novel insights into the influence of amino acid variations in human SAA on the pathogenesis of AA amyloidosis.     

气候舒适度在不同海拔的时空变化特征及其影响因素

气候舒适度是在气候变化背景下评估热量变化的方式之一.本研究基于1984-2013年间贵州省84个气象台站的逐日观测数据,采用通用热气候指数(UTCI)讨论不同海拔的气候舒适度时空变化规律及主要影响因子,定量分析了不同海拔地区各气候因子对UTCI的影响差异.结果表明: 1984-2013年间,贵州省多年平均UTCI与气温在空间分布格局上有很强的一致性,均表现为温度随海拔升高而降低,全省大部分地区年舒适天数在180～240 d之间;贵州省各站点UTCI增幅随海拔升高而增大,且UTCI变化幅度[-0.58～1.38 ℃·(10 a)^-1]高于气温变化幅度[-0.36～0.45 ℃·(10 a)^-1];在全省范围内,UTCI与各气候因子的相关关系由大至小依次为气温、风速、气压、相对湿度和云量,相关系数分别为0.899、-0.855、0.818、-0.373和-0.042;在不同海拔地区,不同因子与UTCI的相关系数变化有很大的不一致性.随海拔升高,UTCI受气温影响逐渐减弱,风速的影响程度增大.     

Menstrual disturbances in chronic renal failure.

Twelve female patients undergoing intermittent hemodialysis (HD) and 5 females posttransplantation (PT) were studied. All the HD patients had menstrual disturbances and 5 had galactorrhea. The mean basal LH level was significantly elevated (p less than .05) in patients on HD compared to normal controls, but the mean LH response to luteinizing hormone releasing hormone (LRH) was not significantly different from the control group. Mean basal FSH and the FSH response to LRH was normal. In the PT pateints the LH response to LRH was significantly greater at 120 min when compared to normal females. In the HD group the serum 17B estradiol, progesterone and testosterone levels were significantly lower than in the controls but in the PT group only testosterone levels were significantly lower. These results differ from those previously found in uremic males. Elevated prolactin levels were found in the patients on hemodialysis and correlated well with the presence of galactorrhea. These was no correlation between the elevated prolactin levels and amenorrhea in the patients on hemodialysis but one PT patient with amenorrhea had elevated prolactin levels.     

Circadian variations in the responsiveness of human gallbladder to sulfated mineral water.

It is well known that the intake of sulfate-containing natural mineral waters leads to contraction of the gallbladder, probably induced by the release of cholecystokinin (CCK). As early as 1959, there were some hints in the literature of circadian variations in gallbladder response; to find out whether this applies with sulfate as a stimulus, a pretest for basic information about gallbladder reaction to sulfate-containing mineral water was carried out on 19 healthy volunteers. On this basis, 15 healthy subjects of both sexes were then studied. After 6h of fasting, 500 mL of a sulfate-containing mineral water (2,800 mg SO4(2-)/L) were ingested within 5 min. The size of the gallbladder was registered ultrasonographically before and 15, 30, 60, and 120 min after drinking. The experiments were carried out seven times at different hours of the day for each volunteer. After the intake of the mineral water, the mean gallbladder size decreased significantly, followed by an increase after 60 min (P < .001). Significant circadian spontaneous variation in gallbladder size was detected (acrophase around 09:00; amplitude was 30.0% of daily average, P < .001). The contraction induced by the sulfate-containing water was most marked in the early morning hours and minimal around mid-day; the amplitude of this variation accounting for 29.0% of the daily average (P < .01). In contrast, the postdrinking relaxation was maximal around 18:00 and minimal around 9:00 (amplitude 38.5%. P < .001). These results show that the basal size of the gallbladder and its reaction to stimuli show a marked circadian variation: Whereas contractibility is maximal in the morning, dilatation is stronger in the afternoon.