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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 1,189 records · Page 66Linked to original sources

Evaluation of an immunological test for occult bleeding from colorectal neoplasia.

A study to determine the reliability of a recently described test, the faecal human haemoglobin test (FHH), specific for human blood, in the detection of colorectal neoplasia, is reported. All of nineteen patients with proven cancers studied were shown to have detectable blood in the stools. Three of five patients with polyps in this series also had detectable blood in the stools by this test. Although three of nineteen control subjects had positive tests, two of these were subsequently found to have bleeding sites, and the third was normal on follow up some weeks later. The findings are discussed in relation to the Hemoccult II (H-O) test results obtained in these subjects, and the implications for the possible future role for this test in screening for colorectal neoplasia.

Adenocarcinoma↗

Assignment of the gene for cytosolic alanine aminotransferase (AAT1) to human chromosome 8.

The segregation of human cytosolic alanine aminotransferase (AAT1) and the individual human chromosomes has been studied in 27 secondary and tertiary rat hepatoma-human (liver) fibroblast hybrids. The staining solution used to visualize AAT activity on starch gels was specific for AAT since it was visualized only when all components of the stain were present. The locus for human AAT1 has been assigned to chromosome 8.

Alanine Transaminase↗

Absorption of NPH-insulin from subcutaneous tissue: a methodological study in pigs.

To elucidate the validity of the indirect method of following insulin absorption from the subcutaneous tissue, i.e. external counting of injected 125-I insulin, the disappearance of 125-I NPH insulin from subcutaneous tissue was measured by a biotelemetric method (external measurement of radioactivity) and by direct determination of radioactivity and insulin in subcutaneous tissue extracted one to 300 min. after injection of 8 units 125-I NPH porcine insulin, 5 mm beneath the surface of the skin in 6 anaesthesized pigs. Furthermore, the appearance of insulin in arterial plasma was measured after inhibiting the endogenous insulin secretion of the pigs by epinephrine and propanolol. The disappearance of radioactivity measured continuously for 5 hours was of first order kinetics with t1/2=462+/-36 min. (mean+/-S.E.M.). The half-life of the injected depot of radioactivity (t1/2) demonstrated a large intra- as well as interindividual variation as seen in diabetics. In tissue extracts a highly significant (2P less than 0.001) correlation was found between radioactivity and insulin (r=0.93), indicating the radioactivity to be representative of insulin. During gel chromatography on Sephadex G 50 M only one peak of radioactivity was seen in all tissue extracts. 300 min. after NPH-insulin injection, however, the specific radioactivity of insulin was significantly higher (2P less than 0.05) than in tissue extracts sampled one min. after NPH insulin injection, indicating a slight accumulation of non-immunoreactive insulin degradation products. A fair correlation (r=0.75, 2 P less than 0.05) was seen between the disappearance of externally measured radioactivity or insulin from tissue extracts and the appearance of insulin in plasma. It is concluded that the insulin absorption coefficient is a relevant and biologically sensible expression of insulin absorption.

Absorption↗

Enteritis in foals induced by rotavirus and enterotoxigenic Escherichia coli.

Colostrum-deprived, colostrum-fed or suckling foals were orally inoculated with foal rotavirus and enterotoxigenic Escherichia coli derived from a calf. Neither agent given alone caused diarrhoea in foals aged 1 or 2 days, although with rotavirus, 2 of the 3 inoculated foals became depressed 3 days after inoculation and all 3 were excreting rotavirus in the faeces. Inoculation of both agents induced diarrhoea in colostrum-deprived, colostrum-fed or suckling foals aged up to 16 days. There was an apparent age-related resistance to diarrhoea which developed between 2 and 3 weeks of age. It was related to failure of rotavirus to establish apparent infection in older foals and was independent of preinoculation maternal antibody.

Animals↗

Experimental colibacillosis in gnotobiotic piglets exposed to 3 enterotoxigenic serotypes.

Three strains of enterotoxigenic Escherichia coli (ETEC) (064:KSNT, K88ac; 020:KSNT, K88ac and 08:K85ab, K99) originally cultured from outbreaks of diarrhoea in piglets a few hours old, were administered orally to gnotobiotic piglets. There was a marked age-related difference in the clinical response to infection between the 3 strains although they all produced heat-stable toxin. All 3 strains produced severe clinical signs of depression, anorexia, vomiting, diarrhoea, followed by dehydration and death in one-day-old piglets. In piglets infected at 3 days of age the two K88+ ETEC caused diarrhoea and death but the K99+ ETEC induced moderate diarrhoea only. In piglets infected at 7 days of age, the 064 strain produced severe diarrhoea and death, and 020 strain caused mild diarrhoea in 3 of 6 piglets with one death while the 08 strain caused no illness. Pathological changes in the intestinal tract associated with these infections were minimal, or absent. Immunofluorescent staining with homologous hyperimmune sera demonstrated adherence of the 3 ETEC strains to the brush border of small intestinal epithelial cells. Fluorescing organisms were observed in all infected piglets irrespective of the severity of clinical signs but the degree and extent of colonisation varied with the age of the piglets and the infecting strain. This may explain the difference in clinical response between the 3 strains.

Animals↗

Regional assignment of the structural gene for human acid beta-glucosidase to q42 leads to qter on chromosome 1.

The structural gene for human acid beta-glucosidase (GBA) has been regionally assigned to a narrow region on chromosome 1 using somatic cell hybridization, specific immunoprecipitation, and assay with the natural substrate. A human fibroblast line, 46,XX,del(1)(pter leads to q42:), was fused with mouse RAG fibroblasts and the heterokaryons were subcloned. All hybrid subclones containing a normal chromosome 1 were positive for GBA. In contrast, subclones with a single del(1) were negative for GBA by both immunoprecipitation and natural substrate assays. These results were consistent with the previous assignment of GBA to the region 1p11 leads to qter and further localized the gene to the narrow region 1q42 leads to qter.

Chromosome Mapping↗

An appraisal of the analytical significance of tooth-lead measurements as possible indices of environmental exposure of children to lead.

The analysis for lead of whole-crowns from deciduous incisors has been used as an index of the cumulative exposure to lead of children during the prenatal period and until the time of shedding the tooth. The lead was determined by solvent extraction followed by atomic absorption, and strict analytical quality control was employed. The concentrations of lead in pairs of central and lateral incisors from children revealed unexpectedly large differences for some individuals.

Child↗

Early normalization of platelet survival by endothelial seeding of Dacron arterial prostheses in dogs.

Current synthetic vascular prostheses do not acquire a complete lining of vascular endothelium in humans or dogs. Seeding of autogenous venous endothelium has bee reported to remedy this defect, but previous studies have been primarily morphologic. To see if venous endothelial seeding caused a measurable decrease in platelet-prosthetic interaction in vivo, serial 111In-labeled platelet survival studies were done in dogs with seeded (N = 8) and unseeded (n = 9) thoracoabdominal Dacron bypass prostheses.l Changes in platelet survival time (PST) were compared with endothelial coverage scores, which were determined by blinded survey of removed prostheses by scanning electron microscopy (SEM). The PSTs before surgery (+/- SD) were 5.02 +/- 0.79 days (seeded) and 5.31 +/- 0.99 days (control) (P = 0.51). Seven weeks after surgery the PSTs were 4.01 +/- 1.10 days (seeded) and 2.67 +/- 0.88 days (control) (P = 0.013). The subgroup of four dogs with seeded prostheses that had complete endothelial coverage showed restoration of the platelet survival pattern to that of the linear decay seen before surgery, SEM studies showed that this normalization of PST occurred despite the presence of small nidi of platelet adhesion on exposed Dacron fibers and irregularities of the endothelial pattern consistent with flow disturbances and venous jet lesions near anastomoses. Endothelial seeding, when technically successful, appears to sharply curtail the degree of platelet interaction with vascular prostheses and restores a normal platelet survival pattern. Longer studies of seeded prostheses are needed to determine if seeding protects against the late complications of intimal hyperplasia and thrombotic occlusion.

Animals↗

Helper cell function of Leukemic Leu-2a+, histamine receptor+, T gamma lymphocytes.

Leukemic cells from a patient with an 11-yr history of chronic lymphocytic leukemia (CLL) were found to have the surface phenotype Leu-1+, Leu-2a+, Leu-3a-, sheep erythrocyte rosette+, IgGFc receptor+. The cells also bore a receptor for histamine inhibitable by cimetidine (H-2). The clonal nature of the proliferation was documented by the presence of a consistent marker chromosome (22-trisomy) in metaphases elicited by culture with T cell growth factors. Although the surface phenotype suggested that these cells might function as suppressor lymphocytes, they had an enhancing effect on the pokeweed- mitogen- (PWM) driven generation of plasma cells and reverse hemolytic plaque-forming cells in vitro. This helper activity was modified neither by irradiation of the leukemic cells nor by removal of a minor population of Leu-3a+ cells, suggesting that the effects were attributable to the CLL cells themselves. In addition to these functions, the CLL cells were active in antibody-dependent cellular cytotoxicity (ADCC) assays in association with expression of Fc receptors for IgG. The ADCC was diminished when a transient loss of the Fc receptor expression was observed. No activity in natural killer cell assays employing K-562 cells or herpes simplex virus- (HSV) infected cells as targets could be attributed to the leukemic clone. These studies indicate that the cell surface phenotype, as defined by monoclonal antibodies, may not always predict the functional state of a particular cell, and suggest that within the Leu-2a+ (TH-2+) population of human lymphocytes, some helper as well as suppressor/cytotoxic cells are to be found.

Antibody-Dependent Cell Cytotoxicity↗

Chromosomal localization of the gene for Gaucher disease.

The structural gene for human GBA has been assigned to chromosome 1 using somatic cell hybridization techniques for gene mapping. The human enzyme was detected in mouse RAG cell-human fibroblast cell hybrids by a sensitive double antibody immunoprecipitation assay using a mouse anti-human GBA antibody. No cross-reactivity between mouse beta-glucosidase and human GBA or GBN was observed. For the initial assignment, fifty-two primary, secondary, and tertiary man-mouse hybrids lines, derived from three separate fusion experiments, were analyzed for human GBA and enzyme markers for the human chromosomes. Without exception, the presence of human GBA in these hybrid clones was correlated with the presence of human chromosome 1 or its enzymatic markers, PGM1 and FH. All other human chromosomes were eliminated by the independent segregation of GBA and their respective enzyme markers and/or chromosomes. Using a RAG-human fibroblast line with a mouse-human rearrangement of human chromosome 1, the locus for GBA was limited to the region 1p11 leads to 1qter. Further regional localization was obtained using subclones of hybrids derived from the fusion of a human fibroblast line, 46,XX,del(1)(pter leads to q42:), with mouse RAG fibroblasts. All hybrid subclones containing a normal chromosome 1 were positive for GBA. In contrast, subclones with a single deleted chromosome 1 were negative for GBA by immunoprecipitation and by the natural substrate assays. These results further localized the gene for GBA to the narrow region, 1q42 leads to 1qter.

Animals↗

Evaluation of glutaraldehyde and hydrogen peroxide for sanitizing packaging materials of medical devices in sterility testing.

External surfaces of packaging materials used for sterile medical devices may introduce contaminants into working areas used for sterility testing. Light wiping with tissues moistened with alkaline 2% glutaraldehyde (Cidex) or 3% hydrogen peroxide effectively reduced counts on 5 X 8 cm strips of packaging material (Tyvek) inoculated with 10(7) spores of Bacillus subtilis. The ability of antimicrobial agents to penetrate packaging material and kill contaminants on the medical device was tested by inoculating filter membranes with ca 100 cells of Pseudomonas aeruginosa or Staphylococcus aureus or ca 100 spores of Bacillus subtilis. A sterile square of test packaging material placed over the inoculated membrane (direct method) or 0.5 cm above the membrane (indirect method) was wiped with the antimicrobial agent. Except for polyethylene film (3 mil), all materials tested, including glassine and several types of coated and uncoated Tyvek, were penetrated by the agents, killing cells on the inoculated membranes. Death rates varied, depending on the organism, packaging material, and testing method. It is suggested that penetration tests be performed before using antimicrobial agents for sanitizing packaging materials during sterility tests.

Aldehydes↗

Castration induces a marked reduction in the incidence of thyroid cancers.

Although thyroid disease in humans predominates in females, the prognosis of thyroid cancer in males is much less favorable. To further explore the role of male sex hormones, we utilized the experimental model of radiation-induced follicular cancer in the rat, studying the effects of castration on tumor development. Microscopic evidence of tumor formation was correlated with the biochemical parameters serum thyroxine (T4), thyrotropin (TSH), and thyrocalcitonin (TC) at 24 months. The incidence of follicular carcinomas in intact males ws 58%, compared to 28% in comparable females. Castration of males caused a reduction in the incidence to 22%. Mean circulating levels of TSH were markedly elevated in all three irradiated groups. Mean T4 levels were reduced significantly only in irradiated castrated animals. TC levels were reduced in all irradiated groups. We conclude that although elevated levels of TSH probably play a significant role in the development of radioactive iodine-triggered follicular thyroid neoplasms in the rat, male sex hormone may also play an important role beyond their known effect on basal and thyrotropin-releasing hormone-stimulated TSH.

Adenocarcinoma↗

Sequence of the yeast iso-1-cytochrome c mRNA.

The nucleotide sequence of the yeast iso-1-cytochrome c (CYC1) mRNA is presented. The mRNA was enriched by hybridization to cloned CYC1 DNA attached to a solid matrix: either nitrocellulose filters or diazobenzyloxymethyl cellulose powder. The sequence of the 5'-end of the mRNA was determined by the extension of a CYC1-specific dodecanucleotide primer; the sequence of the 3'-end was determined using a decanucleotide d(pT8-G-A) primer. The CYC1 mRNA begins 61 nucleotides 5' to the AUG initiation codon, extends through the coding sequence to 172 to 175 nucleotides 3' to the UAA termination codon, followed by the poly(A) tail. There are no intervening sequences. Some of the sequences that the CYC1 mRNA shares in common with other eukaryotic mRNAs are discussed.

Base Sequence↗

Resonance Raman spectra for flavin derivatives modified in the 8 position.

Spontaneous resonance Raman or resonance-enhanced AC-coupled inverse Raman spectra were obtained for 8-mercaptoriboflavin, 8-(dimethylamino) riboflavin, 8-hydroxyriboflavin, and 8-aminoriboflavin all free in solution. These Raman spectra were all similar to one another and markedly different from that of riboflavin. In addition, the Raman spectra of 8-mercaptoflavin bound to the apoproteins of old yellow enzyme, glucose oxidase, and L-lactate oxidase were determined. The Raman spectra of these protein-bound flavins were distinctly different from both those of the above 8-substituted riboflavins and that of riboflavin. An argument is presented in favor of assigning a quinonoid electronic structure to these protein-bound flavins.

Flavins↗