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Biomedical subjects

D Weaver

Publications and source records attributed to D Weaver.

At least 73 records · Page 4Linked to original sources

Introduction of a mu immunoglobulin gene into the mouse germ line: specific expression in lymphoid cells and synthesis of functional antibody.

A functionally rearranged mu heavy chain immunoglobulin (lg) gene was introduced into the germ line of mice. The mu gene encodes a polypeptide which, combined with lambda 1 light chains, shows a specificity for binding the hapten NP. Four transgenic mice harboring 20-140 copies of the foreign mu gene expressed the gene specifically in spleen, lymph node, and thymus at a high level. Purified surface lg-positive B cells, Lyt 2-positive mature T cells, and thymocytes transcribed the foreign mu gene at a similarly high level, suggesting that control of lg gene rearrangement might be the only mechanism that determines the specificity of heavy chain gene expression within the lymphoid cell lineage. No transcription of the foreign mu gene was detected in nonlymphoid tissues with the exception of the heart which expressed the gene at a low level. The transgenic mice had up to 400-fold elevated serum levels of NP binding antibody, which contained a heavy chain with the characteristics of the foreign mu gene. The serum levels of endogenous heavy and light chains in transgenic mice appeared to be the same as in normal mice.

Animals↗

Selective peripancreatic sarcoma metastases from primary gliosarcoma. Case report.

Two phenomena associated with malignant gliomas are: 1) the ability to metastasize systemically, and 2) the capacity to induce sarcomatous transformation within the supportive mesenchyma. An unusual case is presented of selective metastases of the sarcomatous elements of a mixed gliosarcoma. Immunohistochemical cell staining with glial fibrillary acidic protein was used to confirm the presence of abnormal glial elements in the primary brain tumor as well as the absence of such glial elements in the abdominal metastases.

Brain Neoplasms↗

Is there a "gold standard" for human serum vitamin B12 assay?

In a study from four laboratories using two commercial vitamin B12 radioassays (impure hog intrinsic factor concentrate containing both intrinsic factor and R binders (IF + R) to measure total corrinoids and the same concentrate presaturated with cobinamide (Cbi) to block B12 binding sites on R binder (IF + R + Cbi) to measure only cobalamins), the rank order of results was generally the same. The concordance between the two tests for classifying sera as normal or deficient was 91% in 311 serum samples. Three percent of sera below the "true B12" (B12 binding to IF + R + Cbi) normal cut-off point were not below the cut-off point for normal "total B12" (B12 binding to IF + R); 6% of sera below the total B12 normal cut-off point were not below true B12 cut-off point. The correlations between Euglena gracilis and the radioassays were 0.80 and 0.83 in the 50 serum samples that also had E. gracilis serum vitamin B12 levels. Lactobacillus leichmannii serum vitamin B12 levels were determined in 49 of the 311 serum samples and results were comparable with results obtained by four radioassay binder systems: IF + R, IF + R + Cbi, highly purified hog IF, and saliva R binder. The closest correlate with L. leichmannii was radioassay using IF + R as binder (r = 0.93), then IF + R + Cbi (r = 0.92), pure IF (r = 0.80), and pure R (r = 0.73). The key to reliable results appears not to reside in a particular assay but rather in determining for each assay its own range of results in participants determined clinically and morphologically normal vs. participants with deficient vitamin B12 (with B12 deficiency defined independently of a serum B12 assay). When laboratory assay results differ from clinical judgment, further evaluation is the appropriate course. There is no "gold standard" for human serum vitamin B12 assay.

Biological Assay↗

Clouston syndrome: an ultrastructural study.

A previously undescribed French-Canadian family affected with Clouston Syndrome (Hypohidrotic Ectodermal Dysplasia) is described. Ultrastructural study of the hair shows disorganization of the hair fibrils with loss of the cuticular cortex. The SEM findings are consistent with the model, suggesting a biochemical defect in the keratin of the integumentary system.

Child↗

Clinical application of organ specific isoamylases.

Since hyperamylasemia with or without abdominal pain is a frequently encountered problem, serum isoamylase analysis in 52 patients was done to see if the organ source of the amylase would be helpful in a clinical setting. Four patterns of hyperamylasemia were found: 1) AMY1 (salivary) hyperamylasemia; 2) AMY2 (pancreatic) hyperamylasemia; 3) Both AMY1 and AMY2 amylase elevated; and 4) macroamylasemia. A variety of conditions other than pancreatitis were associated with hyperamylasemia, and some patients who were thought on clinical grounds to have pancreatitis had raised levels of AMY1 (salivary) amylase. This study suggests that hyperamylasemia alone is a poor indicator of pancreatic disease, and that isoamylase analysis will improve the accuracy with which amylase determinations are used.

Adult↗

Spontaneous resolution of epidural hematomas. Report of two cases.

Two cases of traumatic epidural hematomas are presented. Both patients were minimally symptomatic, and neither required surgical intervention. It is suggested that the use of computerized tomography in head trauma will reveal a new class of epidural hematoma patients who may be treated conservatively.

Adult↗

Interaction of DNA with cytosolic 3-methylcholanthrene binding proteins from either rat or mouse liver.

The ability of cytosolic 3-methylcholanthrene binding proteins from rat liver to interact with DNA was studied using DNA-cellulose chromatography. Two DNA binding fractions, eluting in 0.15 M KCl (peak 1) and 0.33 M KCl (peak 2), were observed on salt elution from a denatured DNA-cellulose column which had been incubated with rat liver cytosol containing radiolabelled 3-methylcholanthrene. No detectable DNA binding fractions were found when columns containing cellulose alone or native DNA-cellulose were used. Temperature activation of the cytosolic proteins containing 3-methylcholanthrene did not result in a significant difference in DNA binding characteristics when compared with a non-treated sample. The pretreatment of rats with Aroclor 1254 induced peak 1 3.7 fold over control values. An analysis of the proteins present in peaks 1 and 2 from control and induced rats was carried out using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Comparative DNA-cellulose chromatography of cytosolic liver proteins from a cytochrome P-448 inducible mouse strain (DBA/6J) and non-inducible mouse strain (DBA/2J) showed much higher levels of DNA binding by protein bound 3-methylcholanthrene from C57BL/6J hepatic cytosol.

Animals↗

The effect of chemotherapeutic agents on the ultrastructure of transitional cell carcinoma in tissue culture.

Human transitional cell carcinoma was successfully grown in short-term tissue culture in 17 of 29 specimens collected (58 per cent). Morphologic parameters of the explants were studied with light and transmission electron microscopy before and after incubation with either thiotepa or 5-fluorouracil. Thiotepa was found to produce marked acantholysis in 43 per cent of those studied. We postulate that thiotepa acts primarily through breakdown of cell adherence. Changes found with 5-fluorouracil were primarily confined to the nucleus.

Antineoplastic Agents↗

Popliteal pterygium syndrome: a phenotypic and genetic analysis.

Two additional families with popliteal pterygium syndrome are presented. Using previously published pedigrees, as well as the ones reported here, evidence is presented that supports an autosomal dominant mode of inheritance for this syndrome. Analysis of previous familial cases showed a large degree of between and within-family variation. The segregation analysis supports the dominant hypothesis (P=0.5).

Adolescent↗

Interaction of polymorphonuclear neutrophils with Escherichia coli. Effect of enterotoxin on phagocytosis, killing, chemotaxis, and cyclic AMP.

Enterotoxigenic Escherichia coli are associated with noninflammatory diarrhea and stimulate adenylate cyclase activity of mammalian cells, thereby increasing intracellular cyclic adenosine 3',5'-monophosphate (cyclic AMP). Increased concentrations of cyclic AMP in polymorphonuclear neutrophils (PMN) inhibit phagocytosis, candidacidal activity, granule discharge, and chemotactic responsiveness. We examined the effect of enterotoxin on the interaction of human PMN with E. coli. Enterotoxigenic and nonenterotoxigenic strains, including serotypes of E. coli identical except for the presence or absence of the plasmid coding for enterotoxin production, were utilized. Enterotoxigenic and nonenterotoxigenic E. coli, tumbled with PMN, were phagocytized and killed (>97%) equally well, and these strains stimulated PMN hexose monophosphate shunt activity equivalently.However, a chemotaxis assay under agarose demonstrated that filtrates of 10 enterotoxigenic strains were less chemotactic for PMN by 15+/-2% total migration or 46+/-1% directed migration, when compared with 6 non-enterotoxigenic strains (P < 0.001). Inactivation of the enterotoxin by heat (65 degrees C for 30 min) or antibodies formed to E. coli enterotoxin eliminated the inhibitory effect of the enterotoxic filtrates for PMN chemotaxis. Addition of purified E. coli enterotoxin directly to the PMN decreased chemotaxis to E. coli filtrates by 32+/-2% (P < 0.001). These data suggest that the effect was due to the heat-labile enterotoxin. The phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (0.1 mM), which potentiates effects due to an increase in intracellular cyclic AMP, further decreased total PMN migration (random plus directed) toward enterotoxic filtrates to 46% of that to nonenterotoxic filtrates (P < 0.001). Addition of cholera toxin (1 mug/ml), which is similar to E. coli enterotoxin, to the PMN inhibited total migration toward nonenterotoxic filtrates by 16+/-2% (P < 0.001). Exogenous dibutyryl cyclic AMP (2 mM) inhibited total PMN migration toward E. coli filtrates by 32% (P < 0.001). PMN intracellular cyclic AMP levels increased by 220% after 2 h of incubation with purified E. coli enterotoxin. The decreased chemotactic attractiveness of enterotoxic E. coli filtrates appears to be related to the ability of enterotoxin to increase cyclic AMP in PMN. Enterotoxin production by E. coli may be advantageous to the microbe by decreasing its chemotactic appeal for PMN.

Blood Bactericidal Activity↗

Maxillofacial dysostosis.

Four individuals in a single family affected with maxillofacial dysostosis are reported. Maxillary hypoplasia, delayed onset of speech, and poor development of language skills without associated hearing loss are the main characteristics of the syndrome which is transmitted as an autosomal dominant. Cephalometric analysis and speech and hearing evaluation of our patients confirmed the above findings.

Adolescent↗