Search PubMed⌕ Search

Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 919 records · Page 51Linked to original sources

Antigen-specific and non-specific helper activities derived from supernatants of human influenza virus-specific T-cell lines.

A T-cell line (H3) was established by culturing human peripheral blood mononuclear cells with influenza virus A/X31 and maintained in long term culture with Interleukin-2 (TCGF). Supernatants were prepared by culturing these cells overnight in the absence of Interleukin-2 but with A/X31 and irradiated autologous E rosette negative cells as a source of antigen presenting cells, and harvesting by centrifugation. The supernatants were shown to replace T cells in helping E- (B) cells to produce antibody specific to A/X31 which was measured by enzyme immunoassay (EIA). Although maximal help was obtained with autologous or semi allogeneic B cells (in the latter case bearing HLA-DR 3 loci) there was still significant antibody production with allogeneic combinations. The supernatants were subsequently fractionated into specific and non-specific helper activities by gel filtration, giving an approximate mol. wt of 50-70,000 and 10-30,000 for each respectively. The specific HF was shown to be genetically restricted in its action upon B cells and also to generate antibody to A/X31 only. The lower molecular weight material acted on any responding B cell regardless of HLA-DR type and produced antibody non-specifically in culture with E- cells even in the absence of antigen. The apparent lack of restriction was therefore due to the masking effect of non-specific and non-restricted HF(s) on the genetically restricted specific HF produced by this line.

Antibodies, Viral↗

An automated dry-slide enzymatic method evaluated for measurement of creatinine in serum.

We evaluated an automated dry-slide enzymatic method involving creatinine iminohydrolase for measurement of creatinine in serum with the Kodak Ektachem analyzer. The means (and SD) for three commercially available quality-control sera, analyzed during eight weeks, were 9.7 (1.0), 16.6 (0.9), and 61 (2.1) mg/L. The regression equation for 105 samples measured with the Technicon SMAC (x) and Ektachem Analyzers (y) was: y = (0.89 +/- 0.007)x + (1.7 +/- 0.3) mg/L and for 170 samples measured with the Beckman Astra (x) and Ektachem analyzers (y): y = (1.00 +/- 0.005)x - (1.9 +/- 0.16) mg/L. Sixty-one samples from renal-transplant patients showed nearly the same agreement. The enzymatic method had no interference from substances that interfere with many Jaffé methods for creatinine, including acetoacetate. The drugs cephalothin and cephoxitin did not interfere, but 5-fluorocytosine interfered significantly with creatinine in the Ektachem method. Values for several ketone-positive sera were 5 to 10 mg/L higher by the Astra relative to the Ektachem. Grossly hemolyzed or lipemic samples were analyzed without difficulty. We conclude that this enzymatic method for creatinine in serum has the speed and precision necessary for routine clinical laboratory use and, except for one drug, the method appears to be specific for creatinine.

Aminohydrolases↗

Lack of coordinated regulation of lipogenic enzymes in a human breast cell line, SKBr3.

A human breast cell line has been identified which contains prodigious levels of fatty acid synthetase but has a very low capacity for lipogenesis from glucose, lactate or acetate. The fatty acid synthetase from this cell line appears to be structurally and functionally normal, and the low lipogenic capacity of the cells appears to be due to the low activities of other lipogenic enzymes, notably acetyl-CoA carboxylase. Thus, the SKBr3 cell line appears to lack the long-term coordinated control of acetyl-CoA carboxylase and fatty acid synthetase commonly observed in normal lipogenic tissues.

Acetates↗

The free coenzyme A requirement of animal fatty acid synthetase. Participation in the continuous exchange of acetyl and malonyl moieties between coenzyme a thioester and enzyme.

A hypothesis that the existence of common binding sites for acetyl and malonyl moieties on the animal fatty acid synthetase necessitates that free CoA be available continuously to facilitate unloading of inappropriately bound acetyl or malonyl moieties, allowing initial access of an acetyl moiety and subsequent access by malonyl moieties to the site of chain elongation, was formulated and tested. The unloading of acetyl or malonyl moieties from the enzyme was blocked by a CoA-scavenging system and the enzyme was unable to reload with the other substrate; the inhibition was relieved by the addition of CoA or pantetheine. The freely reversible nature of the loading/unloading reaction was established as follows. CoA or pantetheine, but not S-acetyl-N-acetylcysteamine, could act as donor or acceptor for acetyl moieties in the loading or unloading reactions; incubation of fatty acid synthetase, acetyl-CoA, and [G-3H]CoA resulted in the formation of acetyl-[G-3H]CoA in an amount consistent with the predicted equilibrium; and addition of a high concentration of CoA shifted the equilibrium toward unloading, leaving most of the substrate-binding sites vacant. These results support our hypothesis and provide a plausible explanation both for the requirement of free CoA by the fatty acid synthetase and for the observed inhibition of fatty acid synthesis by high concentrations of CoA.

Acetyl Coenzyme A↗

Disproportionate expression of the two nonallelic rat insulin genes in a pancreatic tumor is due to translational control.

The expression of the two nonallelic but highly homologous rat insulin genes (1 and 2) in a transplantable beta-cell tumor is found to be 10-fold higher for rat1 insulin than rat2 insulin, while in normal pancreatic tissue there are approximately equal amounts of each protein. No large sequence rearrangements of the genes were apparent by restriction analysis of the tumor DNA, and both genes were found to be specifically hypomethylated in the tumor as compared with other nonpancreatic tissue. Equivalent amounts of both insulin 1 and 2 precursor transcripts, as well as stable, mature mRNAs were detected in the tumor. However, two-dimensional gel analysis of immunoprecipitated rat1 and rat2 preproinsulins synthesized in vitro revealed a 10:1 ratio of rat1 to rat2 proteins. A 1:1 ratio was obtained when the tumor mRNA was treated in vitro with vaccinia virus capping extract, suggesting a structural modification at the 5' terminus of the rat2 mRNA. These results are discussed in the context of insulin regulation by glucose, shown to be due to translational control.

Adenoma, Islet Cell↗

The sore psoas: a difficult diagnosis in childhood.

Nontuberculous psoas abscess is an unusual disease of childhood. The symptoms closely mimic those of other disorders and delay of treatment is commonplace. Eight children (age range 1.5-12 yr) have been treated for psoas abscess. Each presented with a history of fever (38-40 degrees C) and pain. The pain was localized to the hip (3-right, 4-left) and aggravated by ambulation in 7 cases. In 6 children, there was associated lower abdominal tenderness and flexion of the involved hip at rest with resistance to extension. Only 1 child was correctly suspected of having a psoas abscess. Delay in appropriate therapy averaged 5 days (range 1-20 days). Five children underwent joint aspiration and an additional 3 underwent abdominal exploration prior to diagnosis. Surgical drainage was subsequently performed in each case. A retroperitoneal approach, either flank or inguinal, was employed. Staphylococcus aureus was isolated from all cultures. Primary psoas abscess is seldom included in the differential diagnosis of septic lower abdominal and/or lower extremity pain. It should, however, be considered, particularly in the child with classic findings of psoas irritation.

Abdomen↗

Anaemia in patients with myelomatosis.

Twenty-four untreated patients with myelomatosis were studied in order to characterize their anaemia, using standard haematological and ferrokinetic techniques, together with measurements of circulating erythropoietin, erythropoietin sensitivity of marrow cultures and in vitro measurements of haem synthesis. There is a reduction in total erythroid output by the marrow, together with a minor degree of plasma expansion. In patients with normal renal function there is an appropriate increase in erythropoietin in response to anaemia, but in a few cases there may be reduced response of CFU-E to the hormone in vitro. No abnormality of iron status or haem synthesis was found. One case of folate deficiency was discovered.

Adult↗

Pathogenesis of Lassa virus infection in guinea pigs.

A rodent model for human Lassa fever was developed which uses inbred (strain 13) and outbred (Hartley) guinea pigs. Strain 13 guinea pigs were uniformly susceptible to lethal infection by 2 or more PFU of Lassa virus strain Josiah. In contrast, no more than 30% of the Hartley guinea pigs died regardless of the virus dose. In lethally infected strain 13 guinea pigs, peak titers of virus (10(7) to 10(8) PFU) occurred in the spleen and lymph nodes at 8 to 9 days, in the salivary glands at 11 days, and in the lung at 14 to 16 days. Virus reached low titers (10(4) PFU) in the plasma and brain and intermediate titers in the liver, adrenal glands, kidney, pancreas, and heart. In moribund animals, the most consistent and severe histological lesion as an interstitial pneumonia. In contrast, the brain was only minimally involved. The immune response of lethally infected strain 13 guinea pigs, as measured by the indirect fluorescent antibody test, was detectable within 10 days of infection and was similar in timing and intensity to the fluorescent antibody test response of both lethally infected and surviving outbred animals. In contrast to the fluorescent antibody response, neutralizing antibody developed late in convalescence and was thus detected only in surviving outbred guinea pigs. The availability of a rodent model for human Lassa fever in uniformly susceptible strain 13 guinea pigs should facilitate detailed pathophysiological studies and efficacy testing of antiviral drugs, candidate vaccines, and immunotherapy regimens to develop control methods for this life-threatening disease in humans.

Animals↗

A genetic register for Huntington's chorea in South Wales.

A regional genetic register for Huntington's chorea in South Wales is described, based on previous family studies in this area, which is one of high prevalence for the disorder. The primary role of the register is to help in the efficient delivery of services, including genetic counselling, to affected subjects and relatives, and to monitor changes in the population at risk. The mode of operation of the register is described and the essential importance of strict confidentiality is stressed.

Computers↗