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Biomedical subjects

H Smith

Publications and source records attributed to H Smith.

At least 235 records · Page 13Linked to original sources
PubMed1993

Intrauterine insemination with husband's sperm: comparison of pregnancy rates in couples with cervical factor, male factor, immunological factor and idiopathic infertility.

Intrauterine insemination with husband's sperm (IUI) is offered to couples with infertility due to various causes although there is no general agreement on which of these causes should be so treated. In this report 77 couples were diagnosed as having either cervical factor, male factor, immunological factor or unexplained infertility. Insemination was performed 24-32 hours after a rapid rise in the serum LH level. Two of 16 pregnancies which resulted miscarried, 1 was ectopic and the remainder were full term. Eleven occurred in the cervical factor group, 3 in the immunological factor and only 1 in each of the male factor and unexplained infertility groups. The differences in the number of pregnancies between the cervical factor and male and unexplained infertility groups are significant but not between the groups with cervical and immunological factors. The majority of pregnancies (81%) were achieved in the first 4 cycles. Patients with the cervical factor as the cause of their subfertility are likely to benefit from the IUI with their husband's sperm. The small number of patients with the immunological factor in this study does not allow for a conclusion. In our experience the male factor and unexplained infertility patients are unlikely to benefit from intrauterine insemination with husband's sperm.

Female↗
PubMed1993

Detection of genomic and intermediate replicative strands of hepatitis C virus in liver tissue by in situ hybridization.

Nonisotopic in situ hybridization using a digoxigenin-labeled cDNA probe to the 3' nonstructural region (NS5) of hepatitis C virus (HCV) was performed on liver tissue from 33 patients. The results were compared with PCR detection of HCV RNA performed on 24 of the biopsies. Nonisotopic in situ hybridization correlated well with PCR findings. Hybridization signals were detected, within the cytoplasm and nuclei/nucleoli of hepatocytes, mononuclear, and biliary epithelial cells. In patients with clinically and histologically defined chronic active hepatitis related to active HCV infection, HCV genome was frequently detected in biliary epithelium and correlated well with biliary damage, an otherwise uncommon finding in chronic active hepatitis due to other hepatotropic viruses. Further studies using sense and antisense probes synthesized from the 5' non-coding region of the HCV genome confirmed the localization of positive strand of HCV in the above cell populations. The replicative intermediate strand was also present in all cells, although less frequently observed, apart from biliary epithelium, where negative strand of HCV was undetectable. The findings of HCV genome in liver biopsies of two patients with no significant histological abnormalities may suggest that the damage seen in chronic HCV infection is immune mediated, although the cytopathic effect of the virus may also be important.

Acute Disease↗
PubMed1993

Management of hypocalcemic effects of WR2721 administered on a daily times five schedule with cisplatin and radiation therapy. The New York Gynecologic Oncology Group.

PURPOSE: To determine the effects of the chemoprotective agent, WR2721, administered on a daily x 5 schedule with cisplatin and radiation therapy, on calcium and parathyroid hormone (PTH) levels. PATIENTS AND METHODS: Twenty women with cervical cancer were enrolled in a clinical trial to determine the maximal safe dose of WR2721 plus radiation therapy and cisplatin on a novel daily x 5 schedule. Detailed studies of the effects of WR2721 on calcium and PTH levels were initiated after a patient developed symptomatic hypocalcemia. RESULTS: Treatment with WR2721 resulted in a rapid decline in serum PTH levels within 4 hours, which fell below the lower limits of normal at 24 hours, then returned to within normal limits at 48 hours. In contrast, serum levels of ionized calcium were not affected acutely, and declined by only 7% within 24 hours. However, this small decrease persisted for the 5 days of treatment. Hypocalcemic effects were successfully managed with oral calcium carbonate and calcitriol supplements. In one patient, particularly sensitive to the effects of WR2721, serum levels of ionized calcium decreased to less than 3.0 mg/dL despite oral calcium supplements. CONCLUSION: The effects of WR2721 on serum ionized calcium levels are mediated by direct inhibition of PTH activity; other effects such as inhibition of renal tubular calcium reabsorption cannot be excluded. We recommend that patients treated with WR2721, cisplatin, and radiation therapy receive routine oral calcium and calcitriol supplementation and that serum ionized calcium levels be monitored frequently.

Adult↗
PubMed1993

Cytokine release from human peripheral blood leucocytes incubated with endotoxin with and without prior infection with influenza virus: relevance to the sudden infant death syndrome.

Previous work with a neonatal ferret model for human SIDS had indicated that inflammation caused by a combination of influenza virus and bacterial endotoxin may be a cause of human SIDS. To determine whether cytokines may be involved in this inflammatory response, levels of interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)-alpha were examined, using ELISA assays, in culture supernatants of human peripheral blood leucocytes infected with influenza virus and subsequently incubated with endotoxin. Levels of TNF-alpha were increased compared to cells incubated with virus or endotoxin alone. Levels of IL-1 beta were also increased whereas levels of IL-6 were generally not enhanced. Cytokines appeared within 1-2 h of stimulation with virus or endotoxin and increased subsequently to reach maximum titres between 16 and 20 h post treatment. While levels of cytokine were much lower when determined using bioassays rather than ELISA assays, the pattern of increased yields from cells incubated with virus and endotoxin compared with either alone was still evident. The possible importance of these observations for SIDS victims is discussed.

Cells, Cultured↗
PubMed1993

Comparison of intranasal versus intravenous verapamil bioavailability.

Intranasal verapamil administration may limit intrasubject variability encountered due to the metabolism differences of the d and l-isomers. We simultaneously measured verapamil/norverapamil concentrations, PR interval, heart rate (HR), and mean arterial pressure (MAP) in six healthy volunteers receiving verapamil 5 mg intranasally and intravenously on two separate occasions. Two subjects achieved measurable verapamil concentrations after intranasal administration with a mean bioavailability of 16.1%. Intranasal bioavailability was limited secondary to instillation volume. No relationship between HR, MAP and verapamil concentration was noted. A relationship between mean intravenous verapamil concentration and mean PR interval was observed; however, extensive interpatient variability existed: two subjects demonstrated enough counterclockwise hysteresis to skew mean data. Mean data may falsely represent the verapamil concentration-effect relationship. Intranasal verapamil administration is limited by instillation volume. Development of a concentrated dosage form is necessary to assess bioavailability. Concentration-effect relationships are more accurately described using individual, rather than mean data.

Administration, Intranasal↗
PubMed1993

Homeostatic derangement in the CBA rodent host during the growth of the CaNT tumor.

The purpose of this study was to evaluate some indicators of the pathogenesis of cancer cachexia in which the growth of the CaNT tumor markedly alters the metabolism and induces measurable biochemical changes of the host. An increase of hexokinase and lactate dehydrogenase activities with tumor volume, coupled with the decline of oxygen consumption are shown in this work. Furthermore changes in the mean spin lattice and spin-spin relaxation time values of the tumor provide additional information of the abnormal cellular spatial and metabolic relationships that exists within the tumor. In the liver of the host, the augmentation of the oxygen uptake and specific activities of lactate dehydrogenase and fructose-1,6-diphosphatase shown in this work, reflecting an increase in the glucose metabolism rate and thus, energy expenditure of the host. This may envisage some correlation with the onset of biochemical changes in the homeostatic derangement in the host during the fast growth of the tumor.

Adenocarcinoma↗
PubMed1992

The sialylation of gonococcal lipopolysaccharide by host factors: a major impact on pathogenicity.

The resistance of gonococci in most patients to complement mediated killing by human serum is due to sialylation of their lipopolysaccharide (LPS) which prevents bactericidal antibody from reacting with target sites. Two of the host factors responsible are: cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA), a well-known sialylating agent, and another factor which enhances the transfer of sialyl groups from CMP-NANA to LPS catalysed by a gonococcal sialyltransferase. The bacterial determinant of resistance is a conserved LPS component of about 4.5 kDa which is sialylated at a terminal Gal beta 1-4GlcNAc site on its side chain. The sialylated LPS forms a surface coat which is stainable by ruthenium red and connected with previously described 'capsules'. These observations sparked off an explosion of research. Recent publications show that sialylation of LPS by CMP-NANA affects additional important aspects of gonococcal pathogenicity, notably interactions with antibodies and phagocytes, and rendering the gonococcal surface more 'host-like'. Also, the observations have prompted an examination of LPS from some other pathogens for the presence of sialyl groups with positive results for Neisseria meningitidis and Haemophilus influenzae.

Antibodies, Bacterial↗
PubMed1992

Regulation of low affinity IgE receptor (CD23) expression on mononuclear phagocytes in normal and asthmatic subjects.

Mononuclear phagocytic cells contain low affinity receptors for IgE (Fc epsilon RII or CD23) which induce cellular activation in the presence of specific allergen. These studies were performed to quantify the expression by monocytes and alveolar macrophages of Fc epsilon RII in asthma and to determine biologic response modifiers that regulate Fc epsilon RII. Whereas 2.5 +/- 1.0% of the monocytes obtained from normal volunteers were Fc epsilon RII positive, this increased to 16.7 +/- 2.4% in asthma (p < 0.001). Stimulation of Fc epsilon RII expression on monocytes was shown to be an activity of IL-4 (24.5 +/- 5.9%), granulocyte-macrophage-CSF (28.1 +/- 5.2%), IFN-alpha (15.8 +/- 5.3%), IFN-gamma (10.4 +/- 3.7%), and macrophage-CSF (7.3 +/- 0.7%) but not of IL-2, IL-6, or TNF-alpha. Expression of Fc epsilon RII by these cytokines was associated with the induction of specific mRNA transcripts. Using Fc epsilon RII subtype specific primers in the polymerase chain reaction expansion of cDNA, cytokine-induced receptors were shown to be Fc epsilon RIIb. Alveolar macrophages from nonasthmatic subjects displayed minimal expression of Fc epsilon RII (3.2 +/- 1.2%); however, these receptors were present on 69.2 +/- 6.3% of asthmatic volunteers (p < 0.001). Induction of Fc epsilon RII appears specific for allergic asthma insofar as these receptors are also not expressed in subjects with interstitial lung disease (1.3 +/- 1.3%). As assessed by shift in mean fluorescence, instillation of allergen in the asthmatic's airway further up-regulated Fc epsilon RII on alveolar macrophages by 151 +/- 7%. Up-regulation of Fc epsilon RII in atopic individuals may therefore reflect allergen-induced exposure of mononuclear phagocytes to one or more of these cytokines. These studies suggest a mechanism by which an immunologic stimulus that leads to the production of these cytokines (e.g., allergen or viral infection) would contribute to the development or exacerbation of allergic disease.

Allergens↗
PubMed1992

Tolerance mechanism in experimental ovarian and gastric autoimmune diseases.

Neonatal splenocytes, neonatal thymocytes, or phenotypically mature adult thymocytes, transferred from normal BALB/c mice to syngeneic athymic nu/nu (or SCID) mice, led to autoimmune oophoritis and autoimmune gastritis, with corresponding serum autoantibodies, in the recipients. The overall disease incidence was 73%; the pathology ranged from mild to severe, with complete loss of ovarian follicles and gastric parietal cells. CD4+ neonatal spleen cells and CD4+ CD8- adult thymocytes were required for autoimmune disease induction. Adult spleen cells did not elicit disease, but they prevented disease when co-transferred with neonatal spleen cells. However, in confirmation of an earlier report by Sakaguchi et al., (J. Exp. Med. 161:72, 1985), a subset of adult splenic T cells expressing a low level of CD5 molecules elicited similar autoimmune diseases. Thus, self-reactive T cells responsible for autoimmune disease of the stomach and ovary are not effectively deleted in the thymus, and they exist in the peripheral lymphoid organs of normal mice. We conclude that the functional expression of the self-reactive T cells is ontogenetically regulated; whereas T cells in the neonatal mice readily elicited autoimmune diseases in nu/nu recipients, regulatory cells may render self-reactive T cells in the normal adults unresponsive.

Animals↗
PubMed1992

NMR studies of an FK-506 analog, [U-13C]ascomycin, bound to FK-506-binding protein.

Multidimensional, heteronuclear NMR methods were used to determine the complete 1H and 13C resonance assignments for [U-13C]ascomycin bound to recombinant FKBP, including stereospecific assignment of all 22 methylene protons. The conformation of ascomycin was then determined from an analysis of NOEs observed in a 13C-edited 3D HMQC-NOESY spectrum of the [U-13C]ascomycin/FKBP. This structure is found to be quite different from the solution structure of the two forms of uncomplexed FK-506. However, it is very similar to the X-ray crystal structure of FK-506 bound to FKBP, rms deviation = 0.56 A. The methods used for resonance assignment and structure calculation are presented in detail. Furthermore, FKBP/ascomycin NOEs are reported which help define the structure of the ascomycin binding pocket. This structural information obtained in solution was compared to the recently described X-ray crystal structure of the FKBP/FK-506 complex.

Carbon Isotopes↗
PubMed1992

Effect of polymorphism of an MHC-linked transporter on the peptides assembled in a class I molecule.

Short antigenic peptides bound in the groove of class I major histocompatibility complex molecules enable T cells to detect intracellular pathogens. It has been assumed that structural features of the class I molecule alone select which peptides are bound. It is now demonstrated that a complex polymorphism in one of the major histocompatibility complex-encoded putative peptide-transporter genes is associated with an altered spectrum of bound peptides.

Alleles↗
PubMed1992

The serum resistance of gonococci in the majority of urethral exudates is due to sialylated lipopolysaccharide seen as a surface coat.

Examined before subculture, gonococci in 18 urethral exudates collected from different patients were serum-resistant. For 15 exudates, the resistance was drastically reduced by treatment with neuraminidase and by one subculture on laboratory media. It was restored by incubation with cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA). Electron microscopic examination of gonococci in eight exudates showed a surface structure stained by Ruthenium red which disappeared in most samples when they were treated with neuraminidase. These results were identical with those of previous studies on in vitro grown gonococci which had shown that serum resistance is due to sialylation of a 4.5-kDa conserved component of gonococcal lipopolysaccharide (LPS) by host CMP-NANA, which masks the target site for bactericidal IgM and renders surface LPS stainable by Ruthenium red. The serum resistance of gonococci in the remaining three exudates was not reduced by neuraminidase nor by subculture. The mechanism of this stable resistance is unknown.

Blood Bactericidal Activity↗
PubMed1992

Protein export elements from Lactococcus lactis.

Broad-host-range plasmids carrying alpha-amylase or beta-lactamase reporter genes lacking a signal sequence were used to select export elements from Lactococcus lactis chromosomal DNA that could function as signal sequences. Fragments containing such elements were identified by their ability to direct the export of the reporter proteins in Escherichia coli. Several of the selected export elements were also active in Bacillus subtilis and L. lactis, although the efficiencies depended strongly on the host organism and reporter gene used. The export elements AL9 and BL1 were highly efficient in L. lactis in the expression and secretion of at least two heterologous proteins (Bacillus licheniformis alpha-amylase and E. coli TEM-beta-lactamase). AL9 even permitted growth of this organism on starch as the sole carbon source. Nucleotide sequence analysis of five selected fragments indicated that these encode oligopeptides with the major characteristics of typical signal peptides. The putative expression signals had a limited similarity to previously described expression signals for E. coli, B. subtilis and L. lactis. Differences in both expression and export efficiency are likely to underlie the host-specific effects.

Amino Acid Sequence↗
PubMed1992

Abnormal nondefect zone myocardial thallium washout ratio in patients with reversible thallium defects and normal coronary arteriograms.

Thallium myocardial defects in patients with no angiographic coronary artery stenosis have been attributed to attenuation effects and other artifacts. Of 323 patients having thallium myocardial imaging following dipyridamole infusion, 10 of 159 patients with a segmental perfusion abnormality were found to have no luminal diameter stenosis greater than 20% on coronary angiography and no electrocardiographic (ECG) evidence of myocardial infarction or left bundle branch block. A time-standardized regional thallium washout ratio was calculated as thallium myocardial counts with dipyridamole to counts without dipyridamole. In comparison to 10 age-matched control patients with no evidence of cardiac disease and no myocardial thallium defect, study patients had a lower regional myocardial thallium washout ratio from both the defect and nondefect (1.57 +/- 0.40 versus 2.27 +/- 0.92, p = 0.041) zones. Nine of the 10 study patients had independent evidence of noncoronary heart disease, including echocardiographic or ECG evidence of left ventricular hypertrophy in six patients. In patients with thallium defects and normal coronary arteriograms, a time-standardized regional thallium myocardial washout ratio for the nondefect zone may aid in the differentiation of patients with noncoronary heart disease from those with soft tissue artifacts.

Artifacts↗
PubMed1992

Plasmodium falciparum: cytoadherence of malaria-infected erythrocytes to human brain capillary and umbilical vein endothelial cells--a comparative study of adhesive ligands.

The cytoadherence of Plasmodium falciparum-infected erythrocytes (FCR-3 line) to human brain capillary endothelial cells (HBEC), C32 amelanotic melanoma cells, and human umbilical vein endothelial cells (HUVEC) was studied. The adhesion of infected red cells was HBEC > amelanotic melanoma > HUVEC. The presence or absence of the adhesive ligands ICAM-1 (CD54 or intercellular adhesion molecule 1), ICAM-2, and CD36 (= glycoprotein IV) was determined for each of these cells by indirect immunofluorescence using the monoclonal antibodies RR1/1, 6D5, and OKM 5/OKM 8, respectively. It appeared that a major ligand for the FCR-3 line of P. falciparum with amelanotic melanoma cells and HBECs was CD36. Binding to HUVECs was very low, presumably due to their lack of expression of CD36. HBECs, because of their ease of in vitro propagation, long-term maintenance of cytoadherent properties, and their high degree of adhesiveness, will be useful for in vitro studies of adherence.

Antigens, CD↗