Mathematical models from laws of growth to tools for biologic analysis: fifty years of "Growth"

Mathematical models of size and shape have played a prominent role in the first half century of Growth. In honor of the fiftieth anniversary of the journal, this paper reviews the development of these models. An historical perspective is taken with a focus on the changing context in which mathematical models have been studied. Early models were thought to represent principles or laws of growth. Today, models are viewed as tools for biologic analysis. We trace this contextual shift through specific models developed and used in Growth.     

Recommendations from a multi-study evaluation of proposed criteria for staging reproductive aging.

In 2001, the Stages of Reproductive Aging Workshop (STRAW) proposed bleeding and endocrine criteria for defining the early and late menopausal transition stages. Based on expert consensus, STRAW recommended a shorter interval of amenorrhea than the commonly used 90-day amenorrhea criteria for late transition and a >7-day change in cycle length for early transition. The ReSTAGE collaboration used prospective menstrual calendar data from four cohorts (TREMIN, Melbourne Women's Midlife Health Project, Seattle Midlife Women's Health Study, and Study of Women's Health Across the Nation) to quantitatively evaluate STRAW's recommendations. This empirical assessment supported the STRAW recommendations that (1) > or =60 days of amenorrhea be used to define the late menopausal transition and (2) that early transition is consistent with a persistent 7 or more day difference in length of consecutive cycles. Serum follicle stimulating hormone (FSH) values > or =40 IU/l was an independent marker of the transition and, when occurring together with a bleeding marker, increased prediction of final menstrual period. Such a FSH criterion could be incorporated into the STRAW paradigm to facilitate prediction of proximity of the final menstrual period.     

氯仿重结晶棉酚的质量研究

报道了氯仿重结晶的棉酚的化学性质,样品在不同温度下干燥恒重后,经熔点、薄层层析、紫外光谱、红外光谱、X-射线衍射、热重量分析、元素(C,H,Cl)分析及棉酚合量测定等一系列的分析,确证了在60℃以下棉酚与氯仿成溶剂化物(solvate)。随着干燥温度的升高或在室温长时间的贮存,此现象逐渐消失,100℃真空干燥恒重后成为纯棉酚。     

Perineal exposure to talc and ovarian cancer risk.

OBJECTIVE: We sought to determine whether the use of talc in genital hygiene increases the risk for epithelial ovarian cancer. METHODS: We interviewed 235 white women diagnosed with epithelial ovarian cancer between 1984-1987 at ten Boston metropolitan area hospitals and 239 population-based controls of similar race, age, and residence. RESULTS: Overall, 49% of cases and 39% of controls reported exposure to talc, via direct application to the perineum or to undergarments, sanitary napkins, or diaphragms, which yielded a 1.5 odds ratio (OR) for ovarian cancer (95% confidence interval [CI] 1.0-2.1). Among women with perineal exposure to talc, the risk was significantly elevated in the subgroups of women who applied it: 1) directly as a body powder (OR 1.7, 95% CI 1.1-2.7), 2) on a daily basis (OR 1.8, 95% CI 1.1-3.0), and 3) for more than 10 years (OR 1.6, 95% CI 1.0-2.7). The greatest ovarian cancer risk associated with perineal talc use was observed in the subgroup of women estimated to have made more than 10,000 applications during years when they were ovulating and had an intact genital tract (OR 2.8, 95% CI 1.4-5.4); however, this exposure was found in only 14% of the women with ovarian cancer. CONCLUSIONS: These data support the concept that a life-time pattern of perineal talc use may increase the risk for epithelial ovarian cancer but is unlikely to be the etiology for the majority of epithelial ovarian cancers.     

Biometric measurements in fetuses of different race and gender.

Sonographic fetal biometric measurements on 6082 low-risk patients were compared in the second and third trimesters of pregnancy with respect to fetal race and gender. Ultrasonic measurements were obtained from fetuses of women participating in the Routine Antenatal Diagnostic Imaging with Ultrasound Study (RADIUS), who underwent both an early sonographic evaluation between 15 and 22 weeks' gestation and a later scan between 31 and 35 weeks' gestation. In the 16-21-week scans, male fetuses had significantly larger biparietal diameter measurements compared to female fetuses (estimated difference 0.852 mm, 95% CI 0.737-0.967). There was only minimal difference in biparietal diameter between Black and White fetuses. Femur length was similar in both female and male fetuses, but longer in Black compared to White fetuses (estimated difference 0.808 mm, 95% CI 0.539-1.078).During the 31-35-week scans, male fetuses continued to have larger biparietal diameter measurements compared to female fetuses (estimated difference 1.22 mm, 95% CI 1.04-1.40), and femur lengths were persistently longer in Black compared to White fetuses (estimated difference 0.563 mm, 95% CI 0.234-0.893).Further investigation is necessary to evaluate the effect of these slight differences in morphometric fetal measurements between races and genders, so that we can determine how best to use them for optimizing prenatal care.     

Human fibroblast tissue factor is inhibited by lipoprotein-associated coagulation inhibitor and placental anticoagulant protein but not by apolipoprotein A-II

Studies of proteins that inhibit tissue factor activity have generally been conducted using either an extracted tissue homogenate ("thromboplastin") or tissue factor protein reconstituted into phospholipid vesicles rather than with tissue factor expressed in cell membranes (its physiological environment). In the present study, a human fibroblast cell strain was used to evaluate the effects of lipoprotein associated coagulation inhibitor (LACI), placental anticoagulant protein (PAP), and apolipoprotein A-II (apo A-II) on human tissue factor in cell membranes. LACI was tested from 7.8 to 500 pmol/L on fibroblasts cultured at cell densities ranging from 3,500 to 9,925 cells/well, and caused a progressive inhibition of tissue factor activity. PAP was tested from 3.9 nmol/L to 1 mumol/L at cell densities ranging from 4,500 to 15,400 cells/well and caused up to 83% inhibition of tissue factor activity. Inhibition by these proteins appeared to be influenced by cell density as well as whether the cells were intact or disrupted. Apo A-II, up to 1 mumol/L, did not inhibit the tissue factor activity of intact or disrupted fibroblasts at any cell density examined even though it did inhibit the activity of tissue factor in phospholipid vesicles. Of these inhibitors of tissue factor-dependent activation of factor X, LACI was the most effective in suppressing the generation of factor Xa activity. The effects obtained with apo A-II are clearly dependent on the nature of the tissue factor preparation with which it is tested. The disparity between the inhibitory effect of apo A-II on the activity of tissue factor reconstituted into lipid vesicles and the absence of effect on the activity of tissue factor remaining in cell membranes serves to reemphasize the necessity of reexamining results obtained with model systems using as nearly physiological reagents as possible.     

Behavioral and hormonal effects of attachment object separation in surrogate-peer-reared and mother-reared infant rhesus monkeys

Mother-reared and surrogate-peer-reared rhesus monkeys were separated from their respective attachment objects at 6 months of age and tested for the following 9 weeks to determine their home cage behavior and their pituitary-adrenocortical responses to stress. Both groups displayed a strong immediate behavioral response to separation which was characterized by increases vocalization, increased locomotion, and decreased self-play. However, the surrogate-peer-reared infants showed a subsequent recovery in their levels of self-play whereas the mother-reared infants instead developed stereotypic behavior patterns such as repetitive pacing. The 2 groups displayed similar plasma cortisol responses to weekly sessions in an apparatus equipped with animated toy “monsters.” Mother-reared but not surrogate-peer-reared subjects, however, also manifested elevated cortisol levels when an animal in an adjacent cage was captured and removed for stress testing. Mother-reared infant monkeys thus responded in a stronger and more prolonged manner to the loss of their attachment object than surrogate-peer-reared infants. These results suggest that infant rhesus monkeys form stronger attachments to monkey mothers than to inanimate surrogate mothers, a phenomenon which has not been as clearly demonstrated using other indices of attachment strength.     

Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB

Usher syndrome is recognized as the most frequent cause of hereditary deaf-blindness. Usher syndrome type I (USH1), the most severe form of the disease, is characterized by profound congenital sensorineural deafness, constant vestibular dysfunction, and retinitis pigmentosa of prepubertal onset. This form is genetically heterogeneous and five loci (USH1A-E) have been mapped thusfar. However, only the gene responsible for USH1 B (which accounts for approximately 75% of USH1 cases) has been characterized. It encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted 2215 amino acid sequence. Primers covering the complete myosin VIIA coding sequence as well as the 3' non coding sequence were designed, allowing direct sequence analysis of each of the 48 coding exons and flanking splice sites in seven patients affected by USH1. Four novel mutations were thereby identified. The possibility should now be considered of a sequence-based prenatal diagnosis in some of the families affected by this very severe form of Usher syndrome.