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Biomedical subjects

W Lim

Publications and source records attributed to W Lim.

At least 55 records · Page 3Linked to original sources

Perinatal HIV infection and the effect of zidovudine therapy on transmission in rural and urban counties.

OBJECTIVES: To assess health care providers' identification of human immunodeficiency virus (HIV)-exposed infants, to ascertain the prevalence of transplacental or oral zidovudine treatment among infants exposed to HIV, and to estimate the impact of zidovudine use on perinatal transmission in rural and urban North Carolina. DESIGN: Survey of North Carolina newborns tested for HIV infection in 1993 and 1994 compared with the number of anonymous HIV-positive childbearing women. SETTING: North Carolina hospitals, public health clinics, and private physicians' offices. MAIN OUTCOME MEASURES: Rates of identification of HIV-exposed infants and of perinatal HIV-1 transmission, determined by HIV culture and polymerase chain reaction testing in the infants. RESULTS: The proportion of HIV-exposed children in North Carolina who were identified and tested increased from 60% in 1993 to 82% for all of 1994, and to more than 90% for the last quarter of 1994. The HIV-exposed infants born in rural counties were more likely to be recognized than those born in urban counties (P<.001). In 1994, most infants were evaluated relatively early in life: 39% by 1 week of age, 63% by 6 weeks, and 76% by 3 months. Among infants with recognized HIV exposure, transmission decreased significantly between 1993 and 1994, from 21% to 8.5%, respectively (P=.009). After the announcement of the results of the AIDS Clinical Trials Group Protocol 076, zidovudine was given to 75% of HIV-positive women who delivered infants in North Carolina. Only 5.7% of infants who received any zidovudine became infected, compared with 18.9% of infants who received no zidovudine (P=.007). CONCLUSIONS: Health care providers in North Carolina are identifying most of the state's HIV-seropositive pregnant women, treating them with zidovudine, and testing their infants soon after birth for HIV infection. The use of zidovudine in pregnant women and their infants has reduced perinatal HIV transmission in the state.

AIDS Serodiagnosis↗

Depressor pathway involved in somatosympathetic reflex in cats.

The present study aimed to identify direct vasodepressor pathways from the rostral ventrolateral medulla (RVLM) to the spinal cord and their role in mediation of somatosympathetic reflexes. Vasopressor and depressor areas were identified by stimulating various sites of RVLM electrically and/or chemically in anesthetized cats. Electrical lesions on the pressor areas abolished the pressor response evoked by peripheral C-fiber activation while the depressor response remained. Electrical lesions on the depressor areas decreased the depressor response evoked by A delta-fiber stimulation. To characterize the neurons involved, 17 medullospinal sympathetic neurons were identified electrophysiologically. While most of them were sympathoexcitatory, three medullospinal tract cells were found to be sympathoinhibitory neurons. From these results we concluded that a minor group of neurons in the RVLM is sympathoinhibitory and is involved in mediation of somatosympathetic depressor response.

Animals↗

The primary antibody repertoire of normal, immunodeficient and autoimmune mice is characterized by differences in V gene expression.

During the last decade, the structure and organization of the immunoglobulin heavy and light chain locis have been defined in mice and humans. Studies on VH gene expression at different stages of development, in different organs and disease states have provided useful insight into the construction of a primary antibody repertoire in mice. Clearly, 3'VH genes 7183, Q52 and Vh11, which are conserved during evolution, are preferentially expressed during early development of the B-lymphocyte repertoire. A preferential use for the V kappa 4 gene family is evident during early B-cell development. The initial development of the primary antibody repertoire is therefore influenced by a restricted set of VH and V kappa gene elements. The restricted B-cell repertoire is subsequently normalized in the periphery, as revealed by stochastic VH gene expression, as a result of exposure to environmental antigens. Obviously, the peripheral B-cell pool characterized by stochastic VH gene expression is selectively replenished by newly generated B cells in bone marrow that preferentially expresses 3'VH genes. The V kappa genes are, however, expressed in a non-random manner in the neonatal and adult B-lymphocyte repertoire that is probably related to VH and V kappa association dynamics and/or positive or negative selection. Interestingly, these characteristics of neonatal and adult primary repertoire are noted in both B1 and B2 lymphocytes. No remarkable age-related differences are evident for VH and V kappa gene expression. In healthy mice, both the mitogen responsive (available) and unstimulated (expressed) B-cell repertoire show similar VH gene expression. Interestingly, VH gene expression varies in different organs which may reflect, or occur as a result of, the specialized function of each organ. For example, J558 gene expression is higher in the peripheral LN where B cells continuously encounter exogenous antigens. The skewed VH and V kappa gene expression noted in immunodeficient and autoimmune lupus-prone mice reflects the impairment of the primary antibody repertoire associated with immunodeficiency and autoimmune disorders.

Animals↗

Induction stand.

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Anesthesia, Intravenous↗

Contribution of L- and N-type calcium currents to exocytosis in rat adrenal medullary chromaffin cells.

The excitation-secretion coupling process requires Ca2+ influx through voltage-dependent Ca2+ channels (VDCC) but the contribution of L-type or N-type VDCC during the secretion from adrenal chromaffin cell is still on debate. In this study we explored the contribution of each VDCC to exocytosis in single rat adrenal chromaffin cells. Chromaffin cells were voltage-clamped clamped in the whole-cell recording mode. Ca2+ inward current (ICa) was elicited by depolarization from -70 mV to +10 mV and the change in cell membrane capacitance (Cm) was monitored as an indicator of the resultant exocytosis. The increase in Cm had positive correlation with the amount of ICa and replacing the internal Ca2+ buffer to high EGTA (5 mM) decreased the sensitivity of Cm increase to Ca2+ influx. After blockage of ICa with 100 microM Cd2+, there was no increase in Cm following membrane potential depolarization while INa was intact. To clarify the contribution of each type of VDCC to induce exocytosis during membrane potential depolarization, L- and N-type ICa were blocked selectively by Ca2+ channel antagonists. After blockage of L-type ICa with nicardipine (1 microM), ICa was blocked to 35 +/- 6.2% (mean +/- standard error) of control and the resultant change in Cm was reduced to 38 +/- 4.6% of control. Bay K-8644 (1 microM) enhanced ICa and the similar proportion of Cm was increased by this L-type VDCC agonist. On the other hand omega-conotoxin GVIA (1 microM), an N-type VDCC antagonist, blocked ICa to 60 +/- 4.3% of control and reduced the change in Cm to 58 +/- 3.9% of control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

Mechanism of liposome destabilization by polycationic amino acids.

Polycationic amino acids induce the leakage and fusion of liposomes containing anionic lipids. We have investigated the nature and extent of the changes in membrane physical properties caused by these polypeptides which could result in the observed membrane destabilization. We found that in the range of pH 5 to pH 7 both poly-L-histidine and poly-L-lysine were ineffective in shifting the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine, either in the presence of absence of 1-palmitoyl-2-oleoylphosphatidylserine. We also studied the gel to liquid crystalline phase transition properties of 1:1 mixtures of phosphatidylserine and phosphatidylethanolamine, both in dimyristoyl forms as well as the 1-palmitoyl-2-oleoyl forms, as a function of pH and in the presence and absence of polycationic amino acids. We observed that these two lipids were largely miscible at all pH values and in the presence and absence of the polypeptides. However, there was some increased tendency for phase separation at higher pH and in the absence of polypeptide. Thus neither changes in curvature strain nor lateral phase separation induced by the polycationic amino acids could account for their marked ability to induce leakage and fusion. Phosphatidylethanolamine labelled with pyrene on one of the acyl chains gives rise to fluorescent emission from both monomer and excimer forms. The ratio of emission intensity from these two forms is indicative of lateral phase separation and the degree of lateral mobility of this probe. In equimolar mixtures of the 1-palmitoyl-2-oleoyl forms of phosphatidylserine and phosphatidylethanolamine in the liquid crystalline phase at 30 degrees C we find little effect of pH on the ratio of excimer to monomer emission intensity. However poly-L-lysine markedly lowers the fraction of excimer emission from these liposomes through the pH range from 5 to 7. Poly-L-histidine lowers the excimer to monomer emission ratio at pH 5 but not at pH 7. This is opposite to what one would expect for lateral phase separation and is interpreted at being the consequence of the polypeptide lowering the rate of lateral diffusion of the lipids. This effect of poly-L-histidine is observed over a range of temperatures from 0 to 40 degrees C in both gel and liquid crystalline phases. There is no evidence from the behaviour of the pyrene fluorescent probe for lipid interdigitation.(ABSTRACT TRUNCATED AT 400 WORDS)

Calorimetry, Differential Scanning↗

HIV infection in pregnancy. A review of current developments.

It appears that pregnancy itself is not adversely affected by HIV infection, but the course of HIV infection in the mother may be accelerated by pregnancy. The results of the 076 trial have changed our approach to AIDS in pregnancy. Heretofore AZT was only given for maternal indications such as severe immunodeficiency (CD4 count less than 200). We now recommend that AZT be given to all women with HIV infection and to infants postpartum. As to mode of delivery, Cesarean section may be beneficial, but we await further studies. We strongly encourage all pregnant women to have HIV testing regardless of risk factors. The HIV epidemic is here, in North Carolina. It is our responsibility as doctors to help pregnant women as best we can with their disease.

Acquired Immunodeficiency Syndrome↗

Histoplasma capsulatum infection associated with continuous ambulatory peritoneal dialysis.

Fungal infection has become increasingly more important in patients undergoing continuous ambulatory peritoneal dialysis. We report here a case of Histoplasma capsulatum infection in such a Hong Kong Chinese patient who presented with fever and peritonitis. Histoplasma capsulatum was isolated from the dialysis fluid and histoplasma antibody was detected in the serum. The patient responded to the combined treatment of fluconazole, 5-flurocytosine and amphotericin B. This is the first reported case of histoplasmosis in Hong Kong.

Amphotericin B↗

An investigation of maternal morbidity with identification of life-threatening 'near miss' episodes.

This study was designed to investigate the pattern of obstetric morbidity and to determine the frequency of serious life-threatening episodes as a basis for clinical audit. The records of over 2,000 maternities from a National Health Service Consultant Unit during a six-month period were analysed. Morbidity was noted in almost a quarter of the cases, and life-threatening episodes, termed 'near miss' morbidity, were identified. As the maternal death rate has fallen in this country, maternal morbidity has come to represent a more useful indicator of obstetric care than mortality. The results of this study identify the need for an agreed set of definitions for 'near miss' morbidity, and suggest that not only should it be included for discussion in unit perinatal meetings, but that Regional obstetric morbidity enquiries would provide valuable denominator data on morbidity.

Female↗

In vitro synthesis of human immunodeficiency virus-specific antibodies in peripheral blood lymphocytes of infants.

An assay system was developed for the analysis of antibodies secreted in vitro against human immunodeficiency virus (HIV) by cultured peripheral blood lymphocytes of HIV-infected individuals. Cultures of peripheral blood lymphocytes were established with medium alone or with medium containing Epstein-Barr virus (EBV) or pokeweed mitogen. HIV antibodies were determined by an ELISA performed with commercial kits in which a whole virus extract served as antigen. Optimal antibody secretion was detected in 7-day peripheral blood lymphocyte cultures to which EBV had been added to provide polyclonal B-cell activation. Pokeweed mitogen-induced antibody secretion and spontaneous antibody secretion were less consistent. With EBV as a stimulus, the sensitivity and specificity of this assay for determining HIV infection status were each 100% in adults. When the assay was applied to infants and children, 23 of 24 symptomatic HIV-seropositive children (class P-2) and 11 of 33 asymptomatic seropositive infants aged less than or equal to 15 months (class P-0) tested positive for EBV-induced antibody secretion. Six of the 11 P-0 patients who tested positive have progressed to develop symptomatic disease, while the remainder are still seropositive at ages 2-15 months. Of the infants who were negative in this assay, all have remained asymptomatic. Treatment with 3'-azido-3'-deoxythymidine in infected adults and children has resulted in transient suppression of the in vitro antibody response in some instances. Thus EBV-induced synthesis of HIV-specific antibodies in vitro is a sensitive and specific indicator of HIV infection and is of help in determining infection status of asymptomatic seropositive infants who are classified as having "indeterminate" infection.

Acquired Immunodeficiency Syndrome↗

Continuous varicella-zoster infection associated with acyclovir resistance in a child with AIDS.

Acyclovir has become the treatment of choice for varicella-zoster virus (VZV) infections in immunocompromised individuals. This article describes a 4-year-old girl congenitally infected with human immunodeficiency virus who developed a continuous cutaneous infection with VZV that persisted over a 14-month period until her death. Initial episodes of varicella and zoster were responsive to acyclovir treatment; however, subsequent recurrences necessitated administration of multiple courses of acyclovir. Lesions became markedly hyperkeratotic, slow healing, and persistent despite acyclovir therapy. Numerous attempts to isolate virus from the lesions yielded only one isolate late in the course of therapy. This virus clearly demonstrated acyclovir resistance in vitro. Bizarre manifestations of VZV infection could present both diagnostic and therapeutic dilemmas. Prolonged acyclovir treatment of highly immunocompromised patients with acquired immunodeficiency syndrome and severe VZV may lead to the appearance of resistant virus.

Acquired Immunodeficiency Syndrome↗