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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 1,027 records · Page 57Linked to original sources

Controlled ovarian hyperstimulation: an adjunct to assisted reproductive technology.

Controlled ovarian hyperstimulation was given to a study group consisting of male factor, endometriosis, and unexplained infertility. The aim of the study was to determine whether COH might be of value for such couples in a setting lacking ART facilities. When compared with their own spontaneous cycles or with a control group (untreated but scanned), COH proved significantly better for unexplained infertility. However, COH was not significantly effective for male factor infertility. This study shows that COH should be offered routinely in general hospitals to couples on long-term waiting lists for ART (especially those facing enforced expectant management).

Adult↗

Identification of loci in Arabidopsis that confer resistance to geminivirus infection.

The infection of susceptible plant hosts by single-stranded DNA viruses in the geminivirus group depends on the interaction of host and viral factors for the replication of viral DNA, the expression of viral genes, and the movement of virus throughout the plant. This paper reports that two strains of the geminivirus, beet curly top virus (BCTV) differ in their ability to infect certain ecotypes of Arabidopsis thaliana. Symptoms appeared on susceptible plants approximately 2-3 weeks after inoculation with BCTV-Logan and after 10-15 days with BCTV-CFH. Symptoms were more severe in BCTV-CFH-infected plants and included leaf curling, the formation of stunted, deformed inflorescence structures and the accumulation of anthocyanin pigments in symptomatic tissues. Analysis of viral DNA accumulation indicated that symptom development and severity were correlated with the amount of viral DNA present in the plants. Viral DNA was undetectable in two ecotypes that were phenotypically resistant to BCTV-Logan. Studies of viral DNA replication in excised inflorescence pieces demonstrated that BCTV-Logan could replicate in tissues from these resistant ecotypes, suggesting that resistance was due to a block in viral movement. Genetic studies of these two ecotypes indicate that resistance is due to a single, recessive locus. This is the first example of a single resistance locus to any geminivirus. The identification of resistant and susceptible interactions between different BCTV strains and A. thaliana ecotypes provides an excellent model system for the genetic and molecular analysis of the interaction of a plant host with this important group of plant pathogens.

Arabidopsis↗

Superovulation and timed intercourse: can it provide a reasonable alternative for those unable to afford assisted conception?

Superovulation was performed prospectively with pure follicle stimulating hormone (FSH) to a group of 224 infertile patients with ovulatory factor (51), male factor (60), mild/moderate endometriosis (24) and unexplained infertility (72). The aim was to produce three or four leading follicles in order to compensate for a 'deficient' factor. Ovulation was induced with human chorionic gonadotrophin (HCG) and monitoring was performed entirely by serial transvaginal ultrasound on alternate cycles up to a maximum of six cycles (1120 treatment cycles) with intervening cycles being used as self-controls (932 rest cycles). A further control group of 56 patients was matched for age, category and duration of infertility and was only scanned serially (336 control cycles). Seventy-four pregnancies were achieved and 54 delivered, giving a cumulative pregnancy rate per couple of 33% and a cumulative take home baby rate of 24% per couple after a maximum of six cycles of treatment. When compared with the rest or control cycles, treatment was significantly effective for ovulatory (P < 0.001), mild/moderate endometriosis (P < 0.01) and unexplained infertility (P < 0.01) but not for male infertility. Furthermore, pregnancy was five times more likely during the first four treatment cycles (P = 0.00006, odds ratio = 5) at the expense of a significant multiple pregnancy rate (18.9%) and mild/moderate ovarian hyperstimulation rate (12%). We conclude that four cycles of superovulation should be routinely offered to couples on waiting lists for assisted conception or to those unable to afford it, in anovulatory, mild/moderate endometriosis and unexplained infertility. These results need confirmation by a prospective multi-centre randomized study.

Adult↗

Transient loss of proteins carrying Kell and Lutheran red cell antigens during consecutive relapses of autoimmune thrombocytopenia.

A patient is described in whom two consecutive relapses of autoimmune thrombocytopenic purpura (AITP) were associated with loss of red cell antigens of the Kell and Lutheran blood group systems respectively. During the second relapse the glycoprotein CD44 and to a lesser extent the LW antigen were also depressed. Both relapses were associated with concomitant production of IgG antibody recognizing high-frequency determinants on the corresponding antigen-carrying protein. Blocking of antigen sites by these antibodies was not the cause of reduced antigen expression, because immunoblotting studies showed absence of Kell protein during the first relapse, and Lutheran protein during the second. On both occasions the red cell changes reverted to normal with disappearance of the antibody as the AITP entered remission. There was no evidence of clonal lymphocyte expansion as demonstrated using immunoglobulin JH and T cell receptor beta chain probes.

Adult↗

Hypophysiotropic role and hypothalamic gene expression of corticotropin-releasing factor and vasopressin in rats injected with interleukin-1 beta systemically or into the brain ventricles.

Intact adult male rats were injected intravenously (i.v., 400 ng/kg), intraperitoneally (i.p., 400 ng/kg) or intracerebroventricularly (i.c.v., 100 ng/kg) with interleukin-1 beta (IL-1 beta) or its vehicle. In comparison with vehicle-treated animals, IL-1 beta induced significant (P < 0.01) increases in plasma ACTH levels measured 30 min later regardless of the route of cytokine administration. These changes were markedly blunted in rats administered specific antibodies directed against corticotropin-releasing factor (CRF). In contrast, vasopressin (VP) antibodies significantly blunted ACTH released by the i.c.v. injection of IL-1 beta, but only modestly altered the effect of the systemic injection of the cytokine. We then used semi-quantitative in situ hybridization analysis to measure changes in steady-state mRNA levels, as they might occur in response to these same doses of IL-1 beta. Following administration of the vehicle, measurement of gene expression in the paraventricular (PVN) portion of the hypothalamus indicated a measurable amount of hybridization signals for both CRF and VP. No detectable changes in either CRF or VP gene expression were observed in rats injected with IL-1 beta i.v. or i.p. 5 h earlier. In contrast, the i.c.v. administration of the cytokine significantly (P < 0.01) increased both CRF and VP mRNA levels measured 5 h later. These results suggest that while endogenous CRF modulates the response of the corticotrophs to this cytokine regardless of the route of administration, the role of VP is more important in rats injected centrally than in those injected peripherally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Magnetic resonance imaging evaluation of the effects of ageing on grey-white ratio in the human brain.

A previous neuropathological report noted a non-linear pattern of change in cerebral grey-white matter ratio during ageing. In that report, grey-white ratio decreased from age 20 to age 50, then increased in elderly subjects. The objective of the current study was to attempt to replicate this pattern of age-related change in the grey-white ratio in living human subjects using quantitative magnetic resonance imaging segmentation analysis. We measured the grey-white ratio in 78 subjects between the ages of 19 and 77 years, using a computer segmentation algorithm with magnetic resonance images. In agreement with the previous neuropathological report, the current in vivo magnetic resonance study found that the grey-white ratio declined from age 20 to age 50, then increased in elderly subjects.

Adult↗

Clinical analysis of 40 cases of childhood-onset Behçet's disease.

Behçet's disease is a chronic, relapsing, idiopathic, multi-system condition characterized by mucocutaneous, ocular, gastrointestinal, articular, vascular, urogenital, and neurologic involvement. Usually the onset occurs between 20 and 30 years of age; it is very uncommon in children. We analyzed 40 cases of childhood-onset Behçet's disease. The male:female ratio was 0.67. The most frequent major sign was oral ulceration, appearing in all patients. Other major signs were genital ulcers (33 patients), skin lesions (29), and ocular lesions (11). The average time interval between the initial oral ulceration and the second major manifestation was 8.8 years. After the second major manifestation, the third and fourth features rapidly developed within one to two years. The most frequent minor sign was arthritis, occurring in 11 of 40 patients. Intestinal, neurologic, and renal involvement was also present. From our results, we concluded that oral ulceration, which is the most common initial manifestation, should not be neglected in children, since it may signal Behçet's disease.

Age of Onset↗

Effect of postnatal exposure of female rats to an alcohol diet: influence of age and circulating sex steroids.

We have previously reported that when compared with animals fed ad libitum, adult ovariectomized (OVX) female rats fed an alcohol diet, but not its isocaloric equivalent control, showed a blunted ACTH response to the intravenous injection of interleukin-1 beta (IL-1 beta). The present work was undertaken to determine whether this finding could be extended to intact rats, and whether the stage of sexual maturation and/or circulating sex steroids of ovarian origin modulated the inhibitory influence of alcohol. Intact female rats were exposed to alcohol or pair-fed between postnatal days 25-35 (group I), 35-45 (group II), or 45-55 (group III). Animals of comparable age and fed ad libitum served as controls. All alcohol-exposed animals had similar blood alcohol levels measured during the eighth night of treatment. Group I lost the most weight following exposure to alcohol, but did not show measurable changes in ACTH released in response to 20 or 100 ng IL-1 beta/kg. Both alcohol and pair-feeding caused a modest decrease in IL-1-stimulated ACTH in rats of group II, but only alcohol significantly blunted corticotrophs' activity in group III. Group III, when fed alcohol, also showed lower CRF content in the median eminence compared with absolute controls or the isocaloric diet. No measurable changes, however, were observed in steady-state CRF mRNA levels in the hypothalamus of animals fed any of the diets. When intact and OVX rats were compared at 55 days of age, alcohol feeding caused a decrease in IL-1-induced ACTH secretion which was slightly, though not significantly, larger in intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Prenatal alcohol exposure alters the hypothalamic-pituitary-adrenal axis response of immature offspring to interleukin-1: is nitric oxide involved?

We have previously shown that following prenatal alcohol exposure, immature offspring showed blunted ACTH released in response to the peripheral administration of interleukin-1 beta (IL-1 beta). The present studies were conducted to investigate the role of changes in corticosteroid feedback (measured by altered adrenal responses to ACTH), corticotropin-releasing factor (CRF) content of the median eminence (ME), and the influence of endogenous nitric oxide (NO). The injection of several doses of ACTH failed to indicate measurable differences between the corticosterone responses of offspring born to dams fed ad libitum [control (C)], pair-fed (PF), or fed alcohol [ethanol (EtOH) = E]. CRF content in the ME, taken as an index of the amount of releasable peptide, showed a small, but statistically significant, decrease following prenatal alcohol exposure. A comparable change, however, was also noted in PF rats. As expected, the subcutaneous injection of IL-1 beta (0.5 microgram/kg) induced smaller increases in plasma ACTH levels of E than C pups. The response of PF animals was intermediate between that of E and C rats. Finally, we observed that inhibition of NO formation by the administration of the arginine derivative L omega nitro-L-arginine-methylester significantly augmented ACTH secretion in all three experimental groups, and reversed the decreased corticotrophs' response to IL-1 beta caused by prenatal alcohol. Taken together, our results suggest that the ability of prenatal alcohol exposure to alter ACTH released by immature pups in response to blood-borne IL-1 beta is probably not mediated through changes in adrenal responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Biodistribution and PDT efficacy of a ketochlorin photosensitizer as a function of the delivery vehicle.

C8KC is a new ketochlorin photosensitizer that must be formulated with an emulsifier because of its poor water solubility. In this report, we compare properties of Cremophor EL (CRM) and Tween 80 as delivery vehicles for C8KC. Unlike Tween 80, CRM altered the physical properties of both human and mouse plasma lipoproteins, resulting in decreased electrophoretic mobility of the individual lipoproteins along with the formation of a lipoprotein degradation product: a phospholipid fraction of low buoyant density. In human plasma, where there was sufficient low-density lipoprotein (LDL) for a distinction to be made, CRM caused a shift in binding of a ketochlorin from albumin to LDL and the degraded lipoprotein fraction. In mice bearing the RIF tumor, the use of CRM for drug formulation was associated with longer plasma and tissue persistence of C8KC, and enhanced photodynamic therapy (PDT) efficacy. These results indicate the importance of both sensitizer and vehicle as determinants of PDT efficacy.

Animals↗

Mouse-human immunoglobulin G1 chimeric antibodies with activities against Cryptococcus neoformans.

Passive antibody administration is a potentially useful approach for the therapy of human Cryptococcus neoformans infections. To evaluate the efficacy of the human immunoglobulin G1 (IgG1) constant region against C. neoformans and to construct murine antibody derivatives with reduced immunogenicities and longer half-lives in humans, two mouse-human IgG1 chimeric antibodies were generated from the protective murine monoclonal antibodies 2D10 (IgM) and 18B7 (IgG1). The 2D10 mouse-human IgG1 chimeric antibody (ch2D10) had significantly lower binding affinity than its parent murine antibody (m2D10), presumably because of a loss of avidity contribution on switching from IgM to IgG. The 18B7 mouse-human IgG1 chimeric antibody (ch18B7) had higher affinity for cryptococcal polysaccharide antigen than its parent murine antibody (m18B7). ch18B7 and ch2D10 promoted phagocytosis of C. neoformans by primary human microglial cells and the murine J774.16 macrophage-like cell line. ch18B7 and m18B7 enhanced fungistatic or fungicidal activity of J774.16 cells and prolonged the survival of lethally infected mice. We conclude that the human IgG1 constant chain can be effective in mediating antifungal activity against C. neoformans. ch18B7 or similar antibodies are potential candidates for passive antibody therapy of human cryptococcosis.

Animals↗

Monoclonal antibodies to Cryptococcus neoformans capsular polysaccharide modify the course of intravenous infection in mice.

Immunoglobulin G1 (IgG1) monoclonal antibodies (MAbs) to the capsular glucuronoxylomannan (GXM) were studied for their ability to modify the course of intravenous Cryptococcus neoformans infection in mice. A/J mice were given intraperitoneal injection of 1.0 mg of either a GXM-binding IgG1 MAb (2H1 or 2D10 gamma 1) or the irrelevant isotype-matched control MAb 36-65 prior to intravenous infection. Parameters used to study antibody efficacy were lung and brain tissue fungal burden, lung and brain weights, serum GXM levels, and histopathological examination of lung, brain, heart, kidney, and spleen tissues. Mice given GXM-binding MAb had significantly reduced lung tissue fungal burden as measured by CFU. In contrast to the reduction in lung tissue burden, the reduction in brain tissue burden was small and did not achieve statistical significance. Serum GXM levels were reduced in mice receiving GXM-binding MAb. Histopathological examination revealed reduced numbers of granulomas and C. neoformans organisms in the lungs, brains, and kidneys of MAb 2H1-treated mice relative to control mice. The lungs and brains of mice receiving GXM-binding MAb weighed significantly less than those of control animals, consistent with the reduced inflammation noted histologically. Subendocardial inflammation and kidney cortical infarctions were present in control infected mice but not in MAb 2H1-treated mice. Immunocytochemical staining for polysaccharide antigen revealed a marked reduction in the amount of tissue polysaccharide in mice treated with MAb 2H1 relative to control mice. The results support an useful role for passive antibody administration in C. neoformans infections.

Animals↗

A patient with coexisting narcolepsy and morbid jealousy showing favourable response to fluoxetine.

A 37 year old Chinese man suffered from coexisting narcolepsy and morbid jealousy which were precipitated by head injury 5 years previously. Fluoxetine 20 mg/day reduced his narcoleptic symptoms and morbid jealousy but not his sleepiness. On defaulting treatment, the patient's symptoms and marital problem recurred. A common central serotonin disturbance might be involved in mediating the sleep disorder and associated psychopathology.

Accidents, Traffic↗

Fructose loading induces cardiovascular and metabolic changes in nondiabetic and diabetic rats.

The effects of fructose loading on the integrated cardiovascular function in vivo, glycemic control, glucose tolerance, and plasma lipid levels in nondiabetic and streptozotocin (STZ) diabetic rats were investigated. Endothelial morphology of the thoracic aorta was also assessed with scanning electron microscopy. Fructose-loaded nondiabetic rats exhibited elevated blood pressure and pulse rate, and signs of arterial atherogenesis, such as focal adherence of leukocytes and fibrin to the endothelium. Intraperitoneal glucose tolerance tests revealed a greater increase in plasma insulin in response to glucose challenge in these animals than in the control. Compared with the untreated STZ-diabetic animals, fructose-loaded diabetic rats had significantly greater hyperglycemia, glucose intolerance, and hyperlipidemia and higher blood pressure, but had a similar degree of hypoinsulinemia, cardiac dysfunction, and cardiac enlargement. They also showed signs of early atherogenesis. The central venous pressure and the susceptibilities of the rats to the induction of ventricular arrhythmias by intravenous infusion of aconitine were not significantly affected by either STZ injection or fructose loading. It is concluded that prolonged intake of an excessive amount of fructose has detrimental effects on the cardiovascular system, glucose metabolism, and plasma lipid levels in both nondiabetic and STZ-diabetic rats.

Angiotensin II↗

Pressure-flow relationships in isolated sheep prenodal lymphatic vessels.

The objective of this study was to determine how isolated sheep prenodal popliteal lymphatic vessels responded to transmural and outflow pressure changes. Afferent lymphatics (0.5-1.0 mm diameter) were suspended in an organ bath with both inflow and outflow ends cannulated. Input to the duct was provided from a reservoir filled with Krebs solution. Two types of experiments were performed. In one group, a transmural pressure was applied to the ducts. In a second group of studies, the inflow pressure was fixed (at 2, 4, or 6 cmH2O) and the outflow pressure was increased in 4-cmH2O increments. The transmural pressure-flow relationship was expressed as a bell-shaped curve with pumping increasing up to 18-26 cmH2O and declining at higher pressures. Maximum flow rates averaged 1.4 +/- 0.6 ml/10 min. Greater than 50% of maximum pumping activity was available between approximately 12 and 43 cmH2O. In response to outflow pressures, variable responses were observed. In some vessels, elevations of outflow pressure had little impact on flow rates, until high outflow pressures were attained. In other ducts, pumping declined in response to outflow pressure challenge. With lower inflow pressures (2 or 4 cmH2O), flow rates occasionally increased with elevations of the outflow catheter. In ducts preset with inflow pressures of 6 cmH2O, the mean stop-flow pressure was 60 +/- 4.6 cmH2O. In comparison with previously published data on the pressure-flow relationships in postnodal lymphatics, prenodal vessels pumped over a larger range of transmural or outflow pressures.

Animals↗