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Biomedical subjects

K Lewis

Publications and source records attributed to K Lewis.

At least 145 records · Page 8Linked to original sources

A mutant lymphoma cell line with a defective Thy-1 glycoprotein gene.

We characterized a mutant T-cell lymphoma line selected for the inability to express the Thy-1 glycoprotein. This cell line is a member of the D complementation class of Thy-1- somatic cell mutants, and it lacks detectable cell-surface Thy-1.1 glycoprotein and detectable cytoplasmic Thy-1 mRNA. Southern blot analysis using a number of probes isolated from the cloned Thy-1.2 gene demonstrated that, in the mutant, one copy of the Thy-1 gene is absent from the genome and the other has undergone rearrangement. This rearrangement results from a deletion of the 5' portion of the gene removing the first two alternate exons and promoters and a portion of the second intron. The deletion breakpoint within the mutant Thy-1 gene was localized to within 400 nucleotides by Southern blot analysis. The breakpoint is near two classes of mouse repetitive elements-a mouse B1-family repetitive element and a simple repetitive sequence-suggesting a mechanism of rearrangement leading to the mutation. Southern blot analysis demonstrated that two closely linked molecular markers on chromosome 9 are unaltered, demonstrating that the deletion in this mutant cell line is subchromosomal.

Animals↗

A double-blind study comparing an acellular pertussis-component DTP vaccine with a whole-cell pertussis-component DTP vaccine in 18-month-old children.

An acellular pertussis-component diphtheria-tetanus-pertussis (AC-DTP) vaccine was compared with a currently licensed, whole-cell pertussis-component DTP (WC-DTP) vaccine for reactogenicity and immunogenicity when given as the fourth DTP immunization in sixty 18- to 24-month-old children. Reactions over the first 48 hours were significantly less common in the AC-DTP vaccine recipients, as follows (WC-DTP/AC-DTP): fever, 85%/5%; redness, 70%/12.5%; tenderness, 100%/22.5%; swelling, 35%/10%; fretfulness, 70%/12.5%; anorexia, 35%/2.5%; and vomiting, 10%/0%. Antibody responses to pertussis antigens (agglutinogens, lymphocytosis-promoting factor, and filamentous hemagglutinin), diphtheria toxoid, and tetanus toxoid in AC-DTP vaccine recipients were comparable with those in WC-DTP vaccine recipients. The AC-DTP vaccine evaluated in this trial seems to be as immunogenic as WC-DTP vaccine while being markedly less reactogenic.

Agglutinins↗

Controlled trial of furosemide therapy in infants with chronic lung disease.

To study the effects of furosemide therapy in infants with chronic lung disease (CLD), a double-blind controlled trial was designed. Seventeen infants with evidence of CLD (oxygen requirements greater than 30% at greater than 3 weeks of age and chest radiographic findings consistent with CLD) were studied. Pulmonary function was measured immediately before, and after 48 hours and 7 days of treatment with furosemide (1 mg/kg/12 hr intravenously or 2 mg/kg/12 hr orally) or placebo. Clinical status improved in six of seven infants who received furosemide and in two of 10 infants who received placebo (P less than 0.002). In the furosemide group, ventilator and oxygen requirements decreased (P less than 0.003); minute ventilation, alveolar ventilation, and dynamic compliance increased; and venous admixture decreased (P less than 0.05). There were no significant changes in the placebo group. Our findings suggest that furosemide significantly improves lung function during therapy in infants with CLD and allows earlier weaning from ventilatory support and supplemental oxygen.

Chronic Disease↗

Histochemical studies with a monoclonal antibody raised against a partially purified soluble estradiol receptor preparation from human myometrium.

A monoclonal antibody (D5) raised against affinity-purified cytosol estradiol receptor (REC) from human myometrium has been used to stain human tissues by means of an indirect immunoperoxidase method. Good staining was obtained with ethanol-, glutaraldehyde-, or Carnoy's-fixed material but not with formalin or Bouin's fixation. Cytoplasmic staining of human breast tumors exhibited a highly significant correlation (P less than 0.001) with REC assayed by conventional estradiol-binding assay provided that allowance was made for both staining intensity and cellularity of the tumor; no correlation existed with soluble progesterone receptor content. Both patient age and tumor differentiation influenced staining patterns in the same way as did REC content. Cultured REC-positive human breast tumor cell lines (MCF-7, ZR-75-1, and CA-2) showed positive staining as did cultured epithelium from human milk. Epithelia in normal breast and fibroadenoma exhibited variable staining that rarely reached the intensity seen in REC-positive tumor cells. The staining patterns of human normal endometrium, myometrium, fallopian tube, ectocervix, endocervix, and ovary and neoplastic endometrium and ovary are described. In every situation thus far examined only cytoplasmic staining has been observed.

Adult↗

An open study evaluating the reactogenicity and immunogenicity of a DTP vaccine containing an acellular pertussis component in four to six year old children.

Acellular pertussis vaccines have been used for mass immunization of children in Japan since the fall of 1981, but until recently they have not been evaluated in the United States. We report a trial with a DTP vaccine containing an acellular pertussis component in 36 four to six year old children who had previously received four doses of United States DTP licensed vaccine with a whole cell pertussis vaccine component. The study vaccine contained diphtheria and tetanus toxoids and 300 HA units of Takeda acellular pertussis component. The principle immunizing antigens in the pertussis component of the vaccine were lymphocytosis promoting factor (LPF) and filamentous hemagglutinin (FHA). Local and systemic reactions were monitored during the first 48 hours after vaccination, and pre-immunization and one month post-immunization serum specimens were obtained for antibody assay. The following reaction rates were noted: redness 50%, tenderness 50%, swelling 41%, fever (greater than or equal to 38 degrees C) 3%, drowsiness 17%, fretfulness 14%, anorexia 11%, and vomiting 6%. Pertussis antibody values (preimmunization/postimmunization) were as follows: agglutinin GMT, 1:21/1:100; FHA mean ELISA u, 28 +/- 6/greater than or equal to 229 +/- 47; LPF mean ELISA u, 176 +/- 59/1732 +/- 280. The pertussis component of the study vaccine would appear to be less reactogenic than United States whole cell pertussis vaccines but still immunogenic when given as a booster immunization to four to six year old children. Further studies are needed to assess reactions and immunogenicity in younger and previously unimmunized children.

Anorexia↗

Expression of the Thy-1 glycoprotein gene by DNA-mediated gene transfer.

We isolated a gene encoding the Thy-1.2 glycoprotein from a recombinant library constructed from BALB/c mouse DNA. To evaluate the expression of this cloned gene in different genomic environments, we introduced it into cell lines derived from fibroblast, lymphoid, and neuronal tissues by DNA-mediated gene transfer. When integrated into the genome of mouse L cells, cell-surface Thy-1 can be detected with anti-Thy-1 monoclonal antibodies. These L-cell lines contain between two and four copies of the cloned Thy-1 gene stably integrated in the host genome. After subcloning into a plasmid vector containing the bacterial Eco-gpt gene as a selectable marker, the Thy-1 gene was introduced into the Thy-1-deficient mouse lymphoma AKR1 (Thy-1-d), and the rat neuronal cell line, B50. The resulting transformants also contain two to four copies of the cloned Thy-1 gene but express up to 50-fold more cell-surface Thy-1.2 than the L cell transformants. The expression of vastly differing amounts of cell-surface Thy-1 from similar numbers of genes suggests that the gene encoding this differentiation antigen is under tissue-specific regulation.

Animals↗

Comparison of use by enrolled and recently disenrolled populations in a health maintenance organization.

The demographic characteristics and ambulatory use of health maintenance organization (HMO) members who voluntarily disenrolled from an HMO--those who returned to the alternative health insurance plan--or who involuntarily disenrolled due to job loss or change--were compared with those of persons still enrolled. The database for all three samples was comprised of ambulatory use data for 6 months (July 1979-December 1979). The HMO-enrolled sample made significantly more visits for health services, on the average, than either of the disenrolled samples. Upon controlling for demographic variables (age, sex, family size, and years enrolled), it was ascertained that young to middle-aged women from families of three or more, making visits for chronic problems, made the greater use among the enrolled sample. The relationship of these findings to the risk vulnerability theory of HMO enrollment choice is discussed, and long-term implications for HMOs are presented.

Adolescent↗

Improvement of uremic neuropathy and hypogeusia by dialysate zinc supplementation: a double-blind study.

A reduction in the plasma zinc concentration is a well-recognized complication of hemodialysis. A positive clinical response to zinc therapy under controlled conditions is the most reliable criterion of zinc deficiency. Zinc therapy using a nonproprietary zinc dialysate was evaluated in 12 dialysis patients with proven hypogeusia and polyneuropathy, in a randomized double-blind crossover comparison (preliminary phase, 4 weeks; placebo phase, 12 weeks; initial phase, 12 weeks; final phase, 6 weeks; post phase, 4 weeks). The dosage was related to the zinc plasma and erythrocyte levels, measured weekly. Nerve conduction velocity (NCV) and taste-testing were used to evaluate the effect of treatment at the end of the placebo and therapy phases. There was significant reduction in the recognition and determination threshold level for each of the four qualities of taste. The NCV improved significantly. The plasma zinc level could be elevated in all patients to the desired concentration, using individualized supplementation of dialysate with zinc. The erythrocyte zinc level remained constant, at double the normal value. The plasma zinc concentration fell back to the initial level 6 weeks after conclusion of therapy. We conclude that (1) zinc substitution may provide a specific therapy for uremic polyneuropathy, (2) the observed hypogeusia results from zinc deficiency, (3) long-term therapy is necessary to obtain a constant normal plasma zinc concentration, (4) zinc substitution by dialysate is a suitable and nonstressful method of administration.

Adult↗