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Biomedical subjects

A Chinn

Publications and source records attributed to A Chinn.

13 recordsLinked to original sources

Preventing recurrent second trimester group B streptococcus chorioamnionitis by intermittent prophylactic ampicillin.

BACKGROUND: Whereas carrying group B streptococcus during pregnancy is common, second trimester group B streptococcus chorioamnionitis with intact membranes is rare, and recurrence of the latter problem even more so. CASE: A 38-year-old multipara with a history of recurrent second trimester group B streptococcus chorioamnionitis resulting in pregnancy loss was treated, beginning at 14 weeks' gestation, with monthly prophylactic ampicillin therapy throughout pregnancy and delivered a healthy male infant at term. CONCLUSION: In women with recurrent pregnancy loss due to second trimester group B streptococcus chorioamnionitis, an intermittent prophylactic antibiotic regimen throughout pregnancy might increase the probability of successful pregnancy.

Adult↗

Hormonal regulation of focal adhesions in bovine adrenocortical cells: induction of paxillin dephosphorylation by adrenocorticotropic hormone.

A study of bovine adrenocortical cell shape on adrenocorticotropic hormone (ACTH) challenge showed that the cells round up and develop arborized processes. This effect was found to be (1) specific for ACTH because angiotensin II and basic fibroblast growth factor have no effect; (2) mediated by a cAMP-dependent pathway because forskolin reproduces the effect of the hormone; (3) inhibited by sodium orthovanadate, a phosphotyrosine phosphatase inhibitor, but unchanged by okadaic acid, a serine/threonine phosphatase inhibitor; and (4) correlated with a complete loss of focal adhesions. Biochemical studies of the focal-adhesion-associated proteins showed that pp125fak, vinculin (110 kDa) and paxillin (70 kDa) were detected in the Triton X-100-insoluble fraction from adrenocortical cells. During cell adhesion on fibronectin as substratum, two major phosphotyrosine-containing proteins of molecular masses 125 and 68 kDa were immunodetected in the same fraction. A dramatic decrease in the extent of tyrosine phosphorylation of these proteins was observed within 60 min after treatment with ACTH. No change in pp125fak tyrosine phosphorylation nor in Src activity was detected. In contrast, paxillin was found to be tyrosine-dephosphorylated in a time-dependent manner in ACTH-treated cells. Sodium orthovanadate completely prevented the effect of ACTH. These observations suggest a possible role for phosphotyrosine phosphatases in hormone-dependent cellular regulatory processes.

Adrenal Cortex↗

Transforming growth factor beta1 decreases cholesterol supply to mitochondria via repression of steroidogenic acute regulatory protein expression.

Transforming growth factor-betas (TGF-betas) constitute a family of dimeric proteins that affect growth and differentiation of many cell types. TGF-beta1 has also been proposed to be an autocrine regulator of adrenocortical steroidogenesis, acting mainly by decreasing the expression of cytochrome P450c17. Here, we demonstrate that TGF-beta1 has a second target in bovine adrenocortical cells, namely the steroidogenic acute regulatory protein (StAR). Indeed, supplying cells with steroid precursors revealed that TGF-beta1 inhibited two steps in the steroid synthesis pathway, one prior to pregnenolone production and another corresponding to P450c17. More specifically, TGF-beta1 inhibited pregnenolone production but neither the conversion of 25-hydroxycholesterol to pregnenolone nor P450scc activity. Thus, TGF-beta1 must decrease the cholesterol supply to P450scc. We therefore examined the effect of TGF-beta1 on the expression of StAR, a mitochondrial protein implicated in intramitochondrial cholesterol transport. TGF-beta1 decreased the steady state level of StAR mRNA in a time- and concentration-dependent manner. This inhibition occurs at the level of StAR transcription and depends on RNA and protein synthesis. It is likely that the TGF-beta1-induced decrease of StAR expression that we report here may be expanded to other steroidogenic cells in which a decrease of cholesterol accessibility to P450scc by TGF-beta1 has been hypothesized.

Animals↗

Procollagen types I and III aminoterminal propeptide levels during acute respiratory distress syndrome and in response to methylprednisolone treatment.

Ineffective lung repair in patients with unresolving acute respiratory distress syndrome (ARDS) is accompanied by progressive fibroproliferation, inability to improve lung injury score (LIS), progressive multiple organ dysfunction syndrome (MODS), and an unfavorable outcome. Our aim was to investigate the relationship between fibrogenesis, pulmonary and extrapulmonary organ dysfunction, and outcome during the natural course of ARDS and in response to prolonged methylprednisolone treatment. We investigated 29 patients with ARDS. We obtained serial measurements of plasma and BAL procollagen aminoterminal propeptide type I (PINP) and type III (PIIINP) levels and components of the lung injury score (LIS) and MODS score. A reduction in LIS greater than one point from day 1 to day 7 of ARDS divided patients in improvers (group 1, n = 7) and nonimprovers (n = 22). Nonimprovers included those who were recruited (day 9 +/- 3 of ARDS) into a prospective, randomized, double-blind, placebo-controlled trial investigating prolonged methylprednisolone therapy in unresolving ARDS (group 2, n = 17), and those who died (all by day 10 of ARDS) prior to meeting eligibility criteria for the randomized trial (group 3, n = 5). On day 1 of ARDS, plasma PINP or PIIINP levels were elevated in all patients. By day 7 of ARDS, mean plasma PINP or PIIINP levels were unchanged in group 1 but increased significantly in group 2 (p = 0. 0002) and group 3 (p = 0.03). On day 7, patients with plasma PINP levels less than 100 ng/ml were 2.5 times more likely to survive (95% CI: 0.855-7.314), and patients with plasma PIIINP levels greater than 25 ng/ml were nine times more likely to die (95% CI: 1. 418-55.556). In group 2, patients taking placebo (n = 6) had no change in plasma PINP or PIIINP levels over time, while patients treated with methylprednisolone (n = 11) had a rapid and sustained reduction in mean plasma and bronchoalveolar lavage (BAL) PINP and PIIINP levels. By day 3 of treatment, mean plasma PINP and PIIINP levels (ng/ml) decreased from 100 +/- 9 to 45 +/- 8 (p = 0.0001) and 31 +/- 3 to 12 +/- 3 (p = 0.0008), respectively. After 8 to 15 d of methylprednisolone, mean BAL PINP and PIIINP levels (ng/ml) decreased from 63 +/- 25 to 6 +/- 23 (p = 0.002) and 42 +/- 5 to 10 +/- 3 (p = 0.003), respectively. Estimated partial correlation coefficients indicated that as plasma PINP and PIIINP levels decreased over the first 7 d of methylprednisolone treatment, positive end-expiratory pressure, creatinine, bilirubin, and temperature also decreased, while PaO2:FIO2 increased. In early ARDS, plasma PINP and PIIINP levels are elevated and continue to increase over time in those not improving. Among nonimprovers, those randomized to prolonged methylprednisolone treatment had a rapid and significant reduction in plasma and BAL aminoterminal propeptide levels and similar changes in lung injury and MODS scores. These findings provide additional evidence of an association between biological efficacy and physiologic response during prolonged methylprednisolone treatment of unresolving ARDS.

Adult↗

Morbidity, mortality and sleep-disordered breathing in community dwelling elderly.

A population-based probability sample of elderly individuals (n = 426), who were originally studied between 1981 and 1986 (mean age at initial study was 72.5 years), were followed for mortality. Those with > or = 30 respiratory disturbances per hour of sleep had significantly shorter survival (p = 0.0034), but the respiratory disturbance index (RDI) was not an independent predictor of death. When Cox proportional hazards analysis was done, only age (the strongest predictor), cardiovascular disease and pulmonary disease were independent predictors of death. It may be that factors that are secondary to or associated with sleep-disordered breathing (SDB), such as cardiovascular or pulmonary disease, predispose these elderly to death.

Age Factors↗

Sleep-disordered breathing in African-American elderly.

Although sleep-disordered breathing (SDB) has been shown to be very prevalent in the elderly, little has been done to examine differences between the elderly of different racial groups. It has been well documented that SDB often results in hypertension and that hypertension is more common in African-Americans than in Caucasians. Therefore, one might suspect that SDB might be more common in African-Americans. Caucasians (n = 346) and African-Americans (n = 54) older than 65 yr of age were studied. African-Americans reported less satisfaction with sleep (p = 0.017), more difficulty falling asleep (p < 0.001), more daytime sleepiness (p = 0.0014), and more frequent morning headaches (p = 0.0043). African-Americans napped 0.8 times more frequently per evening (p = 0.05) and 11 min longer per nap (p = 0.019) than did Caucasians, and they showed a trend toward more total sleep time (428 versus 408 min). Of greater interest was the fact that more African-Americans had severe SDB with a relative risk twofold as great (relative risk = 2.13) as that for Caucasians, which was confirmed in a logistic regression analysis where race was associated with the presence of SDB (RDI > or = 30) independently of age, sex, and body mass index. The mean RDI for those African-Americans with severe SDB was significantly higher than that for Caucasians (72.1 versus 43.3; p = 0.014).

Black or African American↗

Umbilical cord growth in human and rat fetuses: evidence against the "stretch hypothesis".

A total of 103 human fetuses between the 7th and 30th week of gestation were obtained from induced abortion (40 fetuses were normal and 63 were abnormal), and the umbilical cord length (UCL) was measured. The UCL increased almost linearly with gestational age among normal fetuses, contrary to the commonly held tenet that the UCL increases exponentially during the second trimester. When UCLs from the 63 abnormal fetuses were compared with those of normal fetuses, 15 fetuses were found to have short UCL and 10 fetuses to have long UCL. Among the 15 fetuses with short UCL, 6 had early amnion rupture syndrome. An unexpected finding among the 10 with long UCL was that 8 of them had oligohydramnios. It has been suggested that the UCL increases in response to tensile forces placed upon it ("stretch hypothesis"); however, our results are inconsistent with this hypothesis because fetuses with oligohydramnios should be less active and their umbilical cords be subject to less stress. In a separate experiment, we studied the normal development of the UCL in rat fetuses and observed an almost linear increase during the whole gestation similar to that seen in humans. This finding is also inconsistent with the "stretch hypothesis" because amniotic fluid volume decreases significantly from day 19 of gestation to term in rats.

Animals↗

T cell proliferative response to interleukin 2: different frequency of responders among CD45R0 and CD45RA subsets.

A proportion of human blood T cells is known to proliferate in cultures containing 10 or more units/ml of interleukin (IL)2, in the absence of exogenously added antigen. A possible explanation for this phenomenon is that the IL2 serves to maintain the proliferation of memory T cells which have recently been activated by antigen in vivo. To test this possibility we therefore separated T cells according to their CD45 (common leukocyte antigen) phenotype into the CD45RO and CD45RA subsets which are associated with memory and naive status, respectively. The frequency of responder cells in limiting dilution analysis of adult MNC was 1:1625 CD45RO cells, 1:2405 for CD45RA cells, and 1:1642 for unseparated cells. CD45RA cells from newborns had a 1:1850 frequency of responders. The IL2 responder cells were predominantly CD3+ TcR alpha beta +, with a minor component of TcR delta cells. There were no differences in the frequency of T cells using V beta 5 and V beta 8 between responding and nonresponding cells. The data argue against a requirement for prior sensitization for a proliferative response to IL2 and give no evidence that the subset of T cells which responds to IL2 differs in phenotype from nonresponsive cells.

Adult↗

Congenital heart disease among spontaneous abortuses and stillborn fetuses: prevalence and associations.

The prevalence, range, and associations of congenital heart disease (CHD) were studied among 400 spontaneous abortuses between 9 and 40 weeks' gestation. Fifty-two (13.0%) cases of CHD were detected. To minimize selection bias the specimens were grouped by external appearance and the prevalence expressed accordingly. CHD was detected in 21 (7.3%) of 289 externally normal and 31 (27.9%) of 111 externally abnormal fetuses. Ventricular septal defect (VSD) was the most frequent CHD found in isolation as well as in combination with extracardiac malformations. Seventy-five percent of isolated CHD was VSD. Forty (69.2%) of the 52 cases of CHD were associated with extracardiac malformations. Chromosomal syndromes were responsible for a minimum of 19.2% of the cases and suspected in up to 36.5%. The most frequent associations involved the musculoskeletal system, central nervous system, abdominal wall, and kidneys. In contrast, studies of liveborn infants have reported 70% of CHD as isolated defects, including many CHD infrequently seen among spontaneous abortuses. This suggests that fetuses with isolated CHD often survive to term, and CHD does not significantly affect the survival of the fetus in utero. Ventricular septum formation may be particularly susceptible to hemodynamic changes and may be indicative of an underlying pathologic condition that also leads to a spontaneous abortion.

Abnormalities, Multiple↗

Long-bone growth in fetuses with Down syndrome.

Short stature is a well-recognized component of Down syndrome. The femur lengths of affected fetuses have been observed to be shorter than normal, with a ratio of actual to expected femur length of less than 0.91 indicating a high risk of trisomy. To further evaluate this finding we have determined the relationship between limb lengths and gestational age in 37 postmortem fetal specimens with trisomy 21. Control values were obtained from 174 normal fetuses. Measurements of the femur, tibia, fibula, humerus, radius, and ulna were made from roentgenograms or by direct measurement of the bone. Most measurements for each bone of the affected fetuses fell below the normal regression line for that bone, but only 3/37 femurs, 4/32 tibias, 5/32 fibulas, 9/32 humeri, 10/32 radii, and 7/32 ulnas fell more than 2 SDs below the mean. The ratios of actual to expected femur lengths were computed and six fetuses with Down syndrome (16.2%) had ratios less than 0.91. The bones of the extremities of fetuses with trisomy 21 are shorter than normal, but the differences are relatively small. The ratio of actual/expected femur lengths was a less efficient predictor of Down syndrome than were either maternal age or maternal serum alpha-fetoprotein tests. The upper extremity bones were shorter than normal more often than were the bones of the lower extremity, and this finding should be explored further in a prospective study.

Bone Development↗

Normal length of the human fetal gastrointestinal tract.

Little information is available on the normal length of the gastrointestinal tract in fetuses or on factors that may affect its growth. To determine normal growth patterns of the fetal intestine, 58 fetuses received in the Central Laboratory for Human Embryology between January 1, 1987, and July 1, 1988, in which no abnormalities were noted on autopsy, were studied. The gastrointestinal tract was removed from the fetus en bloc from the esophagogastric junction to the pelvic floor and dissected. Measurements of stomach, small and large intestines, and appendix length were made and correlated with gestational age as determined by footlength. Overall growth of the gastrointestinal tract as well as that of each component was linear with respect to gestational age. In addition, five fetuses with omphalocele, 16 with cardiac malformations, and 20 with chromosomal abnormalities were studied. The total lengths of the gastrointestinal tracts in the first group were below the normal range in four of five fetuses. Those with cardiac defects had intestinal lengths below the mean, but the measurements were abnormal in only three. In both groups those fetuses with chromosomal abnormalities appeared to have shorter intestinal tracts than those with normal or unknown karyotypes. The gastrointestinal tracts of aneuploid fetuses fell within the normal range until approximately 20 weeks gestation, after which growth decreased. This growth failure may reflect the growth retardation seen in fetuses with chromosomal abnormalities.

Aneuploidy↗

Uterus unicornis with uterus solidaris.

Five patients are presented who manifested a heretofore unreported uterine anomaly: uterus unicornis with uterus solidaris. The condition is illustrated and described in detail. Patients with this anomaly have a good fertility potential, although they may expect a high fetal wastage, frequent premature labor and delivery, increased complications of pregnancy and delivery, and an increased incidence of infants that are small for the pregnancy duration. The importance of laparoscopy in diagnosing this anomaly is emphasized.

Adult↗