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Biomedical subjects

S Wong

Publications and source records attributed to S Wong.

At least 109 records · Page 6Linked to original sources

Role of carboxy-extended forms of oxytocin in the rat uterus in the process of parturition.

The hypothalamic synthetic pathway of oxytocin (OT) involves the synthesis of carboxy-extended forms that serve as intermediate prohormones. We hypothesized that extended forms of OT are synthesized in the late-gestational rat uterus and that they compete for OT receptor binding. Parturition occurs only when the ratio of OT to its extended forms reaches a critical level. We have measured OT and its extended forms using two antisera, one recognizing OT and its extended forms, the other recognizing only mature amidated OT. Uterine tissue concentrations of extended forms of OT were 5- to 30-fold greater than those of OT, and both increased progressively and significantly through late gestation. The ratio of OT to its extended forms did not change significantly. Antagonists of estrogen or progesterone receptors reduced concentrations of extended forms by > 90% and of OT by 50%, though the estrogen antagonist significantly prolonged gestation and the progesterone antagonist induced preterm delivery. Using a muscle bath preparation, extended forms of OT were weak uterine stimulants and did not alter the OT concentration-response curves. Extended forms of OT were two to three orders of magnitude less able than OT to displace radiolabeled OT from late-gestational uterine binding sites. We conclude that uterine carboxy-extended OT prohormones are regulated in part by estrogen and progesterone. However, these extended forms of OT have little direct biological activity and do not compete with OT for receptor binding. Their role in the process of parturition may be confined to acting as substrates for OT synthesis.

Animals↗

Inhibition of PCR by agar from bacteriological transport media.

We observed inhibition of PCR in throat swabs submitted in routine bacteriological transport media. Experimental studies showed that agar, which was extracted with DNA by DNAzol (Gibco BRL, Gaithersburg, Md.), was the inhibitory agent. No inhibitory effect was observed with a transport medium which did not contain agar.

Agar↗

Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells.

As part of the evaluation of porcine cells, tissues, and organs intended for transplantation into humans, we investigated the conditions required to induce expression and release of porcine endogenous retrovirus (PoEV) from primary cells. Pigs contain endogenous retroviral sequences encoding infectious retrovirus, yet little is known about the conditions required to activate the expression and release of PoEV from primary cells. We show here that mitogenic activation of peripheral blood mononuclear cells (PBMC) isolated from the National Institutes of Health (NIH) miniature pig and the Yucatan pig resulted in the activation and release of an infectious type C retrovirus. Coculture of activated porcine PBMC with pig or human cell lines resulted in the transfer and expression of PoEV-specific sequences and the establishment of a productive infection. Sequence comparison of portions of the PoEV pol gene expressed in pig cell lines productively infected with virus derived from NIH miniature pig and Yucatan pig PBMC revealed marked similarity, suggesting that one or a few loci may be capable of being activated to yield an infectious virus. These findings demonstrate that the presence of endogenous viruses in source animals needs to be carefully considered when the infectious disease potential of xenotransplantation is being assessed.

Animals↗

Oxytocin: a paracrine hormone in the regulation of parturition?

The role of oxytocin in parturition is controversial. When considered as an endocrine hormone, the balance of evidence suggests that oxytocin has little involvement in the initiation of labour. However, recent research has demonstrated synthesis of mRNA encoding oxytocin within the pregnant human uterus. This article reviews the hypothesis that oxytocin is an important paracrine (or autocrine) hormone with respect to the control of myometrial contractility in late gestation. Experimental data are provided from humans when possible and from studies using the rat as an experimental model. The processing of oxytocin prohormones in uterine tissues is reviewed and the presence and possible role of carboxy-extended forms of oxytocin in late gestational tissues of rats are discussed. The regulation of oxytocin and its receptor, particularly by oestrogen and progesterone, is reviewed. The inter-relationship between oxytocin and prostaglandins is discussed. Finally, the metabolism of oxytocin within intrauterine tissues and the recent development of specific antagonistic analogues to oxytocin are considered. It is concluded that further clarification of this paracrine system within intrauterine tissues during late gestation could lead to more successful strategies for preventing or arresting preterm labour in women.

Animals↗

Attitudes and beliefs about organ donation among different racial groups.

Many people on the waiting list for organ donation die each year without receiving organs. The shortage of organs is even more pronounced in minority communities. Despite the fact that minorities are at higher risk, they may be less likely to support or consent to organ donation. This investigation was undertaken to study racial factors in organ donation, by focusing on differences in awareness, attitudes, and behavior. Three family practice centers in the Bronx with racially diverse but socioeconomically homogenous communities were studied. The study population consisted of a convenience sample of 163 patients who were approached for participation while they waited to see a doctor. Respondents filled out a 25-item survey that measured demographic information; their exposure to, awareness of, and attitudes toward organ donation; and whether they had signed an organ donor card. The results demonstrated overwhelming support for organ donation across all racial groups. Racial differences were found on awareness of and attitudes toward organ donation, and in the signing of organ donation cards. In contrast to other studies, racial minorities were not less likely than whites to support organ donation. These results suggest that making it easier for racial minorities to obtain organ donor cards could increase their rates of consenting to donate organs.

Adult↗

Fluorine-18-fluorodeoxyglucose dual-head gamma camera coincidence imaging of recurrent colorectal carcinoma.

We report our experience with coincidence detection imaging of 18F-fluorodeoxyglucose (FDG) using a dual-head gamma camera. Scanning of the pelvis and abdomen of a patient with recurrent colorectal carcinoma showed recurrent disease in the pelvic floor and the base of the urinary bladder and metastatic disease in the retroperitoneal space of the pelvis. Although the tumor involving the bladder and pelvic floor was detected by CT and magnetic resonance imaging (MRI), metastatic spread to the retroperitoneal nodes on the left side was detected only by 18F-FDG imaging. Based on the ultrasound, CT, MRI and cystoscopy, a local recurrence of cancer was presumed in our patient. An exploratory laparotomy was performed to resect the tumor in its entirety. At the time of surgery, the retroperitoneal metastasis in the pelvis was confirmed. Had the findings of the coincidence detection imaging study been considered, the patient would have been spared the surgical procedure.

Adenocarcinoma↗

Pharmacokinetics of zileuton and its metabolites in patients with renal impairment.

The pharmacokinetics of zileuton and its conjugated metabolites were evaluated in patients with chronic renal impairment. Five healthy volunteers (creatinine clearance > 90 mL/min), five patients with renal failure requiring hemodialysis, six with mild (creatinine clearance, 60-90 mL/min), eight with moderate (creatinine clearance, 30-59 mL/min), and six with severe (creatinine clearance < 30 mL/min) renal impairment participated in the study. Zileuton was well tolerated by all participants including those with severe renal impairment and those receiving hemodialysis. The pharmacokinetics of zileuton were similar in healthy volunteers; in patients with mild, moderate and severe renal impairment; and in patients with renal failure requiring hemodialysis. The mean metabolite/parent-area ratios for the pharmacologically inactive zileuton glucuronides progressively increased with the decline in renal function. A very small percentage of the administered zileuton dose (< 0.5%) was removed by hemodialysis. Therefore, adjustment in the dose regimen of zileuton does not appear to be necessary for patients with various degrees of renal impairment and patients with renal failure requiring hemodialysis.

Adult↗

Common effects of touch and vision on postural parameters.

Subjects stood upright with the index finger of the right hand either touching a nearby surface gently or not touching it at all and with the eyes either open or closed. Trajectories of the center of pressure (COP) were analyzed as fractional Brownian motion. The extracted parameters were the effective diffusion (D) coefficients and Hurst (H) exponents for short-term time intervals (corresponding to positively correlated random walks) and long-term time intervals (corresponding to negatively correlated random walks). Gentle tactile contact reduced the effective stochastic activity measured by D to the same extent as the availability of vision. Further, touch interacted with time interval in the same way as vision, with the correlated activity closer to H = 0.5 at both time scales when the finger contacted the nearby surface. The results corroborate and extend major features of recent investigations of haptic influences on posture and recent analyses of vision's influence on the fractional Brownian motions of the COP. Discussion focused on (a) the equivalence of expropriospecific information (about the body's orientation to the environment) registered haptically and visually and (b) the possibility that postural sway may reflect exploratory motions in the short term (obtaining information about the postural system) and performatory motions in the long term (using this information).

Adolescent↗

Regulation of the oncogenic activity of BCR-ABL by a tightly bound substrate protein RIN1.

RIN1 was originally identified by its ability to physically bind to and interfere with activated Ras in yeast. Paradoxically, RIN1 potentiates the oncogenic activity of the BCR-ABL tyrosine kinase in hematopoietic cells and dramatically accelerates BCR-ABL-induced leukemias in mice. RIN1 rescues BCR-ABL mutants for transformation in a manner distinguishable from the cell cycle regulators c-Myc and cyclin D1 and the Ras connector Shc. These biological effects require tyrosine phosphorylation of RIN1 and binding of RIN1 to the Abl-SH2 and SH3 domains. RIN1 is tyrosine phosphorylated and is associated with BCR-ABL in human and murine leukemic cells. RIN1 exemplifies a new class of effector molecules dependent on the concerted action of the SH3, SH2, and catalytic domains of a cytoplasmic tyrosine kinase.

Adaptor Proteins, Signal Transducing↗

Prevalence of GBV-C/HGV, a novel 'hepatitis' virus, in patients with aplastic anaemia.

GBV-C or hepatitis G virus (GBV-C/HGV) is a novel RNA virus with similarities to members of the Flaviviridae family, especially hepatitis C. Viral RNA is detected in about 1.5% of American blood donors, with higher prevalence in multiply transfused patients and in individuals with hepatitis or liver disease. Some cases of aplastic anaemia follow apparent non-A, non-B, non-C viral hepatitis, and GBV-C viraemia has been described in three case reports of hepatitis-associated aplastic anaemia. We tested clinical samples from patients with aplastic anaemia with or without recent hepatitis for the presence of GBV-C/HGV. Virus was detected in a total of 15/57 (26.3%) of patients with aplastic anaemia and 12/52 (23.1%) of multiply transfused control patients. Sequencing of the 188 base pair NS3 helicase PCR product in the serum of five individuals indicated the same high degree of sequence variation as has been seen among other isolates of the virus. GBV-C/HGV does not appear to be implicated in the aetiology of aplastic anaemia.

Anemia, Aplastic↗

High prevalence of GB virus C/hepatitis G virus in healthy persons in Ho Chi Minh City, Vietnam.

GB virus C or hepatitis G virus (GBV-C/HGV), a novel Flavivirus, is detected in 1.5% of US blood donors. The prevalence is higher in multiply transfused patients and in persons with liver disease. Because of the increased incidence of hepatitis in Asia, sera from healthy Vietnamese were tested for the presence of GBV-C/HGV RNA by the reverse transcription polymerase chain reaction. Viral RNA was detected in 5.7% of those tested; 6 of 81 volunteer blood donors had positive samples as did 5 of 97 army recruits and 2 of 50 postpartum women. When the 188-bp product from 6 subjects was sequenced, there was 75%-85% homology at the nucleotide level compared with published sequences, indicating a high degree of genotypic variation, even within a putatively well-conserved region of the viral genome. Viremia with this non-cell-associated novel virus appears to be common among normal persons in Vietnam.

Base Sequence↗

Metabolism of oxytocin in rat uterus and placenta in late gestation.

Concentrations of oxytocin (OT) peptide increase in rat uterine tissues at the time of parturition. We have measured the rate of OT metabolism in these tissues in late gestation to determine whether a decrease in OT catabolism is responsible for the increase in OT concentrations. Uterine and placental tissues were obtained from groups of rats at Days 16, 19, 21, 21.5, 22, and after delivery of the first pup. Delivery usually occurs in the early afternoon of Day 22. Some animals were treated with the estrogen receptor blocker tamoxifen, which will delay parturition by approximately 24 h. Cytosolic and microsomal preparations obtained using ultracentrifugation were incubated with radiolabeled OT. Metabolites were separated using HPLC, and enzyme kinetic parameters were calculated. OT was actively metabolized in both uterine and placental tissues. Total oxytocinase activity was similar in the two tissues. In uterine tissues, activity was greater in the cytosolic fractions. In placenta, activity was evenly distributed between the cytosolic and microsomal fractions. The cytosolic fractions of each tissue contained predominantly post-proline endopeptidase activity, whereas the microsomes contained predominantly aminopeptidase activity. There was a slight trend to decreasing oxytocinase activity with advancing gestation in both subcellular fractions, but this was statistically significant only in the microsomal fraction. The maximal decline in activity was only 25-50%. Tamoxifen treatment had no effect on oxytocinase activity. We conclude that rat uterine and placental tissues contain post-proline endopeptidase and aminopeptidase activities that metabolize OT. It is doubtful that changes in these activities are major factors in regulating the increase in OT concentrations measured in rat intrauterine tissues at the time of parturition.

Aminopeptidases↗

A discharge scoring system for patients with total hip replacement.

Total hip replacement is a common and expensive procedure. Any attempt to shorten the length of hospital stay safely is desirable. Proposes a scoring system specifically designed for this patient population, to determine the optimal timing of safe discharge and postacute care placement. Discusses its implications for the quality of patient care.

Arthroplasty, Replacement, Hip↗

Effects of RU486 on estrogen, progesterone, oxytocin, and their receptors in the rat uterus during late gestation.

Oxytocin (OT) and its receptor (OTR) are synthesized in the endometrium and myometrium of the pregnant rat during late gestation. Both are regulated by estrogen and progesterone (P4), and tissue concentrations of both increase markedly before parturition. The P4 antagonist RU486 will induce parturition in the rat. The purpose of the present studies was to investigate changes in OT and OTR messenger RNA (mRNA) and peptide synthesis within the pregnant rat uterus during RU486-induced parturition. Pregnant rats were given a single injection of RU486 (2.5 mg/rat in oil) on day 15 of pregnancy (normal delivery occurs on day 22). Control animals received injections of oil only. Groups of animals (n = 5 in each group) were euthanized at 0, 6, 12, 24, and 48 h after injection and during labor (immediately after delivery of the first pup). Maternal serum estradiol (E2), P4 and uterine OT, and PGE2 concentrations were measured by RIA. Prostaglandin F2alpha and estrogen receptor levels were measured by enzyme immunoassay (EIA). OTR and P4 receptor (PR) were measured using radioligand-binding assays. OT, OTR, and estrogen receptor mRNAs were measured with ribonuclease protection assays. The average time to delivery, after RU486 injection, was 27.0 +/- 1.2 h. Serum E2 and P4 levels were increased slightly, but significantly, at 24 h after RU486. In controls, OT mRNA increased significantly, and this increase was blocked in the RU486 treatment group. OTR mRNA levels increased within 6 h of RU486 and remained elevated until delivery. OTR peptide was increased by 12 h. PGE2 and PGF2alpha were increased 3-fold and 16-fold, respectively, but not until after the increase in OTR had occurred. We conclude that the mechanism of action of RU486 is to inhibit the P4 suppression of OTR synthesis, allowing increased expression of OTR, which may directly stimulate myometrial contractions or act indirectly through increased synthesis of PGs.

Animals↗