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Biomedical subjects

L Williams

Publications and source records attributed to L Williams.

At least 289 records · Page 16Linked to original sources
PubMed1985

A unique late mechanical complication of jejunoileal bypass.

The consequences of jejunoileal bypass include not just metabolic derangements, though the frequency and severity of these problems have led to the procedure being abandoned in the treatment of morbid obesity, but a variety of mechanical complications as well. In this report, a new mechanical complication is presented: Intussusception of the defunctionalized ileum into the sigmoid colon, an intussusception caused by malignant lymphoma of the ileum. Because the patient had pain but no evidence of obstruction, the ileal tumor was fortuitously discovered during flexible sigmoidoscopy.

Adult↗
PubMed1985

Cell mediated immunity to liver fluke antigens during experimental Fasciola hepatica infection of cattle.

Cell mediated immunity (CMI) to Fasciola hepatica antigens was detected by lymphocyte proliferation and interleukin-2 (IL-2) production tests in cattle during the first 4 weeks following liver fluke infection. From the fifth week of infection onwards peripheral blood lymphocytes were unresponsive to fluke antigens by these in vitro tests. Investigations into the cause of this unresponsiveness found no evidence to suggest a selective loss of the IL-2 producing lymphocyte sub-population or that macrophages were responsible for the suppression or that antigen responsive cells were being sequestered in the spleen and mesenteric lymph nodes. Tests carried out on culture supernatants demonstrated the production during this unresponsive period of factors capable of suppressing in vitro responses to PHA. Although further tests failed to show antigen specific suppressor factors the presence of MHC restricted suppressor factors could not be ruled out. The early and transient appearance of CMI during F. hepatica infection of cattle indicates that delayed type hypersensitivity is unlikely to be important in protective immunity in cattle.

Animals↗
PubMed1985

Biotransformation and elimination of [2-14C]-1-(2-deoxy-2'-fluoro-beta-D -arabinofuranosyl)-5-iodocytosine in immunosuppressed patients with herpesvirus infections.

The metabolism of the drug [2-14C]-1-(2'-deoxy-2'-fluoro-beta-D -arabinofuranosyl)-5-iodocytosine (FIAC), a potent inhibitor of herpesvirus replication, was studied in immunosuppressed patients with herpesvirus infections. FIAC was administered intravenously by 15-min infusion and by mouth 24 h later to four patients at doses of 50 or 100 mg/m2. FIAC was cleared from the plasma primarily by biotransformation in liver, kidney, and peripheral blood, with a terminal-phase half-life of 0.92 to 1.80 h (mean, 1.36 h) after intravenous administration. The area under the concentration-time curve from zero to infinity (AUC0-infinity) for FIAC was 1.6 to 4.7% (mean, 3.4%) of the AUC0-infinity for total radioactivity. 1-(2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) was the major metabolite; the AUC0-infinity for FIAU was 54.3 to 72.5% (mean, 63.4%) of the AUC0-infinity for total radioactivity. The terminal-phase half-life for FIAU was 3.32 to 4.49 h (mean, 3.91 h); FIAU was cleared from plasma by renal elimination and further biotransformation. lesser amounts of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)uracil, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine, the glucuronide conjugates of these metabolites, and the glucuronide conjugates of FIAC and FIAU were also formed. A comparison of the AUC0-infinity for total radioactivity after intravenous and oral administration suggested that nearly all of the oral dose was absorbed. Plasma levels of FIAU, also a potent inhibitor of herpesvirus replication in vitro, exceeded the 50% effective dose for herpes simplex virus and varicella-zoster virus as late as 12 h after administration of FIAC.

Adult↗
PubMed1985

Influence of transport energization on the growth yield of Escherichia coli.

The growth yields of Escherichia coli on glucose, lactose, galactose, maltose, maltotriose, and maltohexaose were estimated under anaerobic conditions in the absence of electron acceptors. The yields on these substrates exhibited significant differences when measured in carbon-limited chemostats at similar growth rates and compared in terms of grams (dry weight) of cells produced per mole of hexose utilized. Maltohexaose was the most efficiently utilized substrate, and galactose was the least efficiently utilized under these conditions. All these sugars were known to be metabolized to glucose 6-phosphate and produced the same pattern of fermentation products. The differences in growth yields were ascribed to differences in energy costs for transport and phosphorylation of these sugars. A formalized treatment of these factors in determining growth yields was established and used to obtain values for the cost of transport and hence the energy-coupling stoichiometries for the transport of substrates via proton symport and binding-protein-dependent mechanisms in vivo. By this approach, the proton-lactose stoichiometry was found to be 1.1 to 1.8 H+ per lactose, equivalent to approximately 0.5 ATP used per lactose transported. The cost of transporting maltose via a binding-protein-dependent mechanism was considerably higher, being over 1 to 1.2 ATP per maltose or maltodextrin transported. The formalized treatment also permitted estimation of the net ATP yield from the metabolism of these sugars; it was calculated that the growth yield data were consistent with the production of 2.8 to 3.2 ATP in the metabolism of glucose 6-phosphate to fermentation products.

Biological Transport, Active↗
PubMed1985

Phase I and II clinical and pharmacological study of 4-demethoxydaunorubicin (idarubicin) in adult patients with acute leukemia.

Fifty-two adults treated previously with either acute leukemia (43 patients) or blastic-phase chronic myelogenous leukemia (nine patients) received 4-demethoxydaunorubicin (20 to 45 mg/sq m) i.v. over 2 to 3 days. Three of the ten patients with acute lymphocytic leukemia achieved a complete remission (CR) lasting 5 to 7 weeks. Five of the 28 patients with acute nonlymphocytic leukemia achieved a CR lasting 5 to 80 weeks. All remissions were induced with one course of treatment with a median time to CR of 28 days (range, 22 to 40 days). None of the patients with blastic chronic myelogenous leukemia or secondary leukemia achieved a CR. The drug was well tolerated; mucositis (36%), nausea and vomiting (35%), and hepatic dysfunction (26%) were the most common side effects. Pharmacokinetic observations on five patients demonstrated multiphasic clearance of 4-demethoxydaunorubicin and extensive formation and prolonged retention of 4-demethoxy-13-hydroxydaunorubicin; that metabolite accumulated in plasma on repeated daily dosing. 4-Demethoxydaunorubicin has sufficient antileukemic activity in both acute lymphocytic leukemia and acute nonlymphocytic leukemia to warrant a prospective comparison, in combination regimens, against the conventional anthracyclines, daunorubicin and/or doxorubicin.

Acute Disease↗
PubMed1985

The etiology of transient endothelial changes in the human cornea.

To investigate the etiology of contact lens-induced transient endothelial changes (blebs) in the human cornea, the effects of five different stimuli on corneal thickness and the appearance of the corneal endothelium were assessed. The stimuli included: (1) a silicone contact lens; (2) a silicone contact lens in combination with anoxia; (3) anoxia alone; (4) a thick hydroxyethyl methacrylate (HEMA) contact lens; and (5) a gas mixture of 9.8% carbon dioxide, 20.5% oxygen, and the balance nitrogen. The silicone lens alone produced no significant alteration in endothelial appearance and little change in corneal thickness. However, when nitrogen gas was passed in front of the lens, a typical bleb response was observed. This indicates that the physical presence of a contact lens is insufficient by itself to produce transient endothelial changes. Anoxia alone induced corneal swelling and endothelial bleb formation, indicating a metabolic component in the bleb response. The gas mixture containing 9.8% carbon dioxide also altered the endothelial appearance but had no significant effect on corneal thickness. The thick HEMA lens produced changes in both the appearance of the endothelium and corneal thickness. The only factor common to the stimuli which induced blebs would appear to be their ability to change the pH in or near the corneal endothelial layer.

Adult↗
PubMed1985

Phase I and clinical pharmacological evaluation of 4'-deoxydoxorubicin in patients with advanced cancer.

We have conducted a Phase I and initial clinical pharmacological evaluation of 4'-deoxydoxorubicin (4'-DXDX), administering the drug i.v. on an every 21-day schedule to 60 patients with advanced cancer. Patients were treated at six dosage levels ranging from 10 to 35 mg/sq m. Leukopenia was the dose-limiting toxic effect, and no cardiac, renal, or hepatic toxicity was observed; stomatitis was not seen; and there were no drug-related deaths. Significant alopecia was rare at doses less than 35 mg/sq m, mild nausea and vomiting occurred in one-third of patients at myelosuppressive doses; 12 patients had a transient local urticarial reaction. In the 30 patients with measurable disease, two partial remissions were seen, lasting 5 months in a patient with a nasopharyngeal adenocarcinoma, and 7 months in a patient with endometrial adenocarcinoma. The recommended dose of 4'-DXDX for Phase II studies is 30 mg/sq m in good-risk patients and 25 mg/sq m in moderate-risk or heavily pretreated patients. Pharmacokinetic studies were carried out in ten patients, four of whom received 4'-DXDX at a dose of 10 mg/sq m and six at 30 mg/sq m. Disappearance of 4'-DXDX from plasma was triphasic with a rapid initial phase clearance showing a t1/2 alpha of 1 to 2 min and a prolonged terminal phase with a median t1/2 gamma in excess of 90 h in patients receiving 30 mg/sq m.

Adult↗
PubMed1984

Creating awareness.

Explore the source record for details and available documents.

Education, Nursing, Continuing↗
PubMed1984

Definition of three species-specific monoclonal antibodies recognizing antigenic structures present on human embryonal carcinoma cells which undergo modulation during in vitro differentiation.

Three novel species-specific monoclonal antibodies 5.1.H, 8.7.D and 13.7.A raised against semi-purified detergent solubilized fractions of the Tera 1 embryonal carcinoma (EC) cell line are restricted in their in vitro distribution to undifferentiated human EC cell lines. Competition experiments have established that distinct antigenic specificities are seen by the 3 different monoclonal antibodies. All 3 antigens 5.1.H, 8.7.D and 13.7.A, defined by these monoclonal antibodies, undergo developmental regulation and cease to be expressed on Tera 2 clones 5 and 12 after retinoic-acid-induced differentiation and on LICR LON HT 39/7 cells after phorbol-ester-induced differentiation. These results taken together with the extremely limited in vivo tissue distribution of the defined antigens suggest that the 5.1.H, 8.7.D and 13.7.A monoclonal antibodies define distinct onco-foetal antigens.

Animals↗
PubMed1984

Familial apolipoprotein CII deficiency: a preliminary analysis of the gene defect in two independent families.

We have used a cDNA clone for human apolipoprotein CII (apo CII) to study the apo CII genes in two independent individuals with familial apo CII deficiency. With all the restriction enzymes so far used, gene fragments hybridising with apo CII cDNA are observed that are indistinguishable from normal samples. This demonstrates that in neither of these individuals is the defect due to a major deletion of DNA in or around the apo CII gene. We have used a common polymorphism of the apo CII gene detected with the enzyme TaqI to follow the inheritance of the gene in the families of these apo CII deficient individuals. The pattern of inheritance that we observe is consistent with the defect causing apo CII deficiency being in, or closely linked to the apo CII structural gene.

Apolipoprotein C-II↗
PubMed1984

An ultrastructural study on the "meconium corpuscles" in rat foetal intestinal epithelium with particular reference to apoptosis.

During the embryonic development of the intestine, programmed deletion of epithelial cells plays a vital role in the formation of secondary lumina and of villi. Electron microscopy shows that this deletion is effected by apoptosis, a distinctive mode of cellular death recently recognised as being implicated in normal tissue involution in the adult, as well as during intrauterine development. The process involves cellular condensation and budding to form membrane-bounded apoptotic bodies containing well-preserved organelles. These are then either engulfed by neighbouring principal cells or sloughed off into the intestinal lumen. Engulfed apoptotic bodies that show various degrees of lysosomal degradation have previously been referred to as "meconium corpuscles".

Animals↗
PubMed1984

Interleukin 2 (IL-2) production by mitogen stimulated bovine peripheral blood lymphocytes and its assay.

Culture medium from bovine peripheral blood mononuclear cells stimulated with the mitogens phytohaemagglutinin (PHA) or Concanavalin A (Con A) was found to maintain the proliferation of Con A blasts in vitro. The factor responsible for this activity was not absorbable with bovine erythrocytes or fresh peripheral blood lymphocytes but was removed by Con A blasts. Production of this factor was dependent on the dose of mitogen used and was greatest after 24 h culture compared to 48 h. Quantitative determinations of factor activity in supernatants were carried out by regression analysis of logit transformed data from assays measuring the maintenance of Con A blast proliferation by supernatants.

Animals↗
PubMed1984

The Collaborative Lipid Research Clinics Program Family Study. III. Transformations and covariate adjustments of lipid and lipoprotein levels.

Several methods of transformation and covariate adjustment have been applied to the Collaborative Lipid Research Clinics Program Family Study data to facilitate analysis of lipid levels of examinees of different sex and age groups. After several exploratory analyses, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were logarithmically transformed, and triglycerides were transformed by the power -0.25. Two types of covariate adjustment procedures, the regression and Z score methods, were used. A modified regression method was developed and was found to be preferable to both simple cubic regression and the Z score method on theoretical and empirical grounds. Refinements in this method to correct for change in variance with age, and for the effect of socioeconomic status, seasonality, and anthropometric measures were made. Methodological issues connected with the transformation and adjustment procedures are discussed.

Adolescent↗
PubMed1984

Suppurative pylephlebitis due to pseudodiverticulosis coli.

Patients manifesting suppurative pylephlebitis and intrahepatic abscess formation secondary to pseudodiverticulosis coli and acute diverticulitis are uncommon, but have very high morbidity and mortality. As illustrated by this case report, the symptoms and signs such a patient manifests are nonspecific and the diagnostic modalities available may be insufficiently sensitive. The therapeutic options available at present are excision and drainage of any detected extrahepatic or intrahepatic septic focus and prolonged antibiotic administration.

Adult↗