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Biomedical subjects

M Weaver

Publications and source records attributed to M Weaver.

At least 91 records · Page 5Linked to original sources
PubMed1988

Restricted production of interleukin 4 by activated human T cells.

Interleukin 4 (IL-4) is secreted by activated T cells and pleiotropically modulates both B- and T-lymphocyte function. In murine helper (CD4+) T-cell clones IL-4 production appears to be regulated independently of interferon gamma and interleukin 2. To determine whether production of these lymphokines is also differentially regulated in uncloned human T cells, we studied lymphokine production by normal human peripheral T cells and T-cell subsets after in vitro polyclonal activation. After maximal induction of lymphokine expression, IL-4 mRNA was detectable in less than 5% of CD4+ and 1-2% of unfractionated T cells, whereas approximately 33% and 60% of CD4+ cells expressed detectable mRNA for interferon gamma and interleukin 2, respectively. This finding correlated with dramatically lower production of IL-4 mRNA and protein than of interferon gamma and interleukin 2 by peripheral blood and tonsillar T cells. The helper-inducer (CD4+ CD45R-) T-cell subset, which significantly enhances in vitro immunoglobulin production, accounted for the preponderance of IL-4 mRNA accumulation and protein production by CD4+ T cells; nevertheless, cells with detectable IL-4 mRNA constituted less than 10% of the CD4+ CD45R- subset. Limitation of IL-4 production to a comparatively small population of normal human T cells could selectively regulate the effects of this lymphokine in T-cell-mediated immune responses; such selective regulation may be a fundamental mechanism for restricting the potentially pleiotropic effects of certain lymphokines to appropriate responder cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

The structure and function of dental-care markets. A review and agenda for research.

The growth of dental health services over the past 15 years has produced several issues in dentistry. Because economic markets are the cornerstone of dental delivery in the US, informed responses to these issues require a thorough understanding of dental-care markets. The empirical literature is reviewed to examine the structure of dental markets, to assess the major determinants of market equilibrium, and to examine the social and health consequences of dental-care markets. Results reveal that while dental markets are imperfectly competitive, it is unclear whether prices exceed competitive levels. Little is known about the effects of dental markets on public oral health and society. Future research is proposed in two broad areas: 1) updating early studies conducted when few Americans had dental insurance benefits; and 2) path-breaking research to advance our knowledge of dental-care markets in particular and medical-care markets in general.

Community Participation↗
PubMed1987

Transient blastemia in phenotypically normal newborns.

Two normal appearing infants presented in the newborn period with elevated white blood cell counts and immature blast cells. Initial bone marrow karyotype analysis showed trisomy of chromosome 21 in all metaphases. In both patients blastemia spontaneously resolved and percentage of trisomy 21 cells decreased. One infant required multiple exchange transfusions and pericardiotomy. The other patient had undifferentiated blasts and continued to have subtle hematopoietic abnormalities greater than 2 years later. Both children have had normal growth and development. The clinical course of these patients emphasizes the need for aggressive supportive care without use of cytotoxic drugs in phenotypically normal newborns with blastemia showing trisomy 21.

Down Syndrome↗
PubMed1986

Oral neomycin and erythromycin compared with single-dose systemic metronidazole and ceftriaxone prophylaxis in elective colorectal surgery.

A prospective randomized trial was performed to compare oral neomycin and erythromycin with single-dose intravenous metronidazole and ceftriaxone in elective colorectal surgery. The study was discontinued after 60 patients were entered. The overall rate of infection was 41 percent in the oral neomycin and erythromycin group (n = 29) compared with 9.6 percent in those who received intravenous metronidazole and ceftriaxone (n = 31) (p less than 0.01). Infections in the oral group were principally due to resistant Staphylococcus aureus, Bacteroides fragilis, and Escherichia coli. Preoperative administration of oral neomycin and erythromycin was associated with a significant reduction of Escherichia coli counts (1 X 10(7) to 3 X 10(5) organisms/ml, p less than 0.05) compared with the intravenous group, but there was no significant reduction in the counts of Bacteroides fragilis (2 X 10(8) to 1 X 10(7) organisms/ml) and there was an increase in the counts of Clostridia (2 X 10(4) to 1 X 10(6) organisms/ml). These results indicate that single-dose systemic prophylaxis with appropriate antibiotics is superior to oral neomycin and erythromycin.

Administration, Oral↗
PubMed1986

Prognostically significant classification of immune changes in AIDS with Kaposi's sarcoma.

Sixteen immunological parameters were assessed quantitatively for their value in providing an immunologically-based and prognostically significant classification of the immune alteration in 97 patients with AIDS and Kaposi's sarcoma (AIDS-KS). The dimensions of reductions in the T4 (T helper-inducer cells) subpopulation of lymphoid cells in the T4-T8 ratio were found to correlate most closely with prognosis. Most other immunological changes did not relate to clinical course. T4 lymphocyte levels greater than 300/microL and a T4-T8 ratio greater than 0.5 indicated a relatively good prognosis, eg, 85% to 95% survival at 12 months. T4 levels less than 100/microL and/or a T4-T8 ratio less than 0.2 had a very poor prognosis, eg, less than 25% survival at 12 months. Intermediate T4 levels and T4-T8 ratios had intermediate prognosis. These immunological findings were found to have independent prognostic value for survival when compared with disease classifications based on tumor stage (I through IV) or on clinical status A (without) or B (with fever, night sweats, or weight loss). Reduced proliferative capacity, increased OKT10 antigen expression, elevated levels of serum IgA, and immune complexes also correlated with prognosis. Elevated levels of serum IgG, cellular HLA-DR expression, and skin test anergy occurred frequently in AIDS-KS but did not have prognostic significance. Variations in level of total lymphocyte, T8 (T suppressor/cytotoxic) cell, gamma FcR receptor-positive cell number, NK activity, or level of serum IgM were less common in AIDS-KS and did not correlate with prognosis.

Acquired Immunodeficiency Syndrome↗
PubMed1985

The Vancouver Lymphadenopathy-AIDS Study: 4. Effects of exposure factors, cofactors and HTLV-III seropositivity on number of helper T cells.

Results of testing for antibody to human T-lymphotropic virus (HTLV-III) and absolute numbers of helper T cells in 219 participants in the Vancouver Lymphadenopathy-AIDS (acquired immune deficiency syndrome) Study were analysed. The mean absolute helper T-cell counts in the 141 HTLV-III seronegative and the 78 seropositive men were 897/mL and 659/mL respectively (p less than 0.001). Established AIDS risk factors such as elevated lifetime number of male sexual partners and frequent receptive anal intercourse did not appear to have any significant effect on number of helper T cells that was independent of HTLV-III antibody status. Seropositive men with less than 100, 100 to 500 or more than 500 male sexual partners in their lifetime had mean absolute helper T-cell counts of 667/mL, 651/mL and 662/mL respectively. Most other risk factors, as well, did not appear to exert any effect on absolute number of helper T cells that was independent of the effect of HTLV-III antibody status. However, independent effects of a history of mononucleosis or hepatitis and of cigarette smoking were noted. The data support the hypothesis that no immune dysfunction beyond that due to the initial infection alone arises from repeated exposure to HTLV-III. Most risk factors appear to act as exposure factors, exerting their effect on the immune system merely by increasing the probability of contact with the agent. The independent effects of a history of mononucleosis or hepatitis suggest that viral agents may be cofactors in the production of immune dysfunction.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Lymphocyte subpopulations in ataxia-telangiectasia.

Peripheral blood lymphocyte subsets were analyzed in nine patients with ataxia-telangiectasia (AT) and their immediate family members. Absolute lymphocyte numbers were slightly low. T-helper/inducer cell, as well as B-cell, percentages were comparable to normal in patients with AT. The percentage of T-suppressor/cytotoxic cells was decreased in five of nine patients. The percentage of large granular lymphocytes was elevated in three patients. No generalities consistent with a disease hypothesis could be made on the basis of lymphocyte subpopulation data.

Ataxia Telangiectasia↗
PubMed1984

Nontransmission of T-cell subset abnormalities from hemophiliacs to their spouses.

Hemophiliacs who are exposed to pooled clotting factor concentrate constitute one group at increased risk for development of acquired immune deficiency syndrome. To determine the prevalence of cellular immune aberrations in asymptomatic hemophiliacs, we studied a group of 65 adult hemophiliacs for T-cell subset abnormalities. Sixty-five percent of concentrate recipients had an abnormal T-helper to T-suppressor cell ratio, 40% had a depressed absolute T-helper cell level, and 29% had an elevated absolute T-suppressor cell count. To determine whether horizontal transmission of T-cell subset abnormalities from hemophiliacs to their female sexual partners occurred, we studied 41 spouses. We found no correlation between paired husband and wife values for T-cell ratio or any other immune parameter studied. There were no significant differences found between wives of hemophiliacs with reversed T-cell ratios and wives of hemophiliacs with T-cell ratios of 1.0 or greater, with respect to immunologic tests. We conclude that there is no evidence to date for heterosexual or household-contact transmission of T-cell subset abnormalities from hemophiliacs to their spouses in our study population.

Adolescent↗
PubMed1984

Quantitative changes in T helper or T suppressor/cytotoxic lymphocyte subsets that distinguish acquired immune deficiency syndrome from other immune subset disorders.

Quantitative measurements of the immune cell subgroups, T helper (Leu 3+/OKT4+) cells and T suppressor/cytotoxic (Leu 2+/OKT8+) cells, were made in patients having acquired immune deficiency syndrome (AIDS) with Kaposi's sarcoma and in patients with AIDS and opportunistic infection, as well as in three other relevant populations. These included patients with lymphadenopathy syndrome, e.g., homosexually active males with lymphadenopathy who sought medical care for additional symptoms, and healthy male homosexuals, as well as a control population. Decrease in the number of T helper cells is characteristic of AIDS with Kaposi's sarcoma or opportunistic infection. Augmentation of the T suppressor/cytotoxic cell population is rare in AIDS with Kaposi's sarcoma but is more frequent in AIDS with opportunistic infection. Augmentation of the T suppressor/cytotoxic cell population, however, may occur in a variety of circumstances, including cytomegalovirus and other viral infections, in healthy, homosexually active males, and in otherwise healthy hemophiliac subjects receiving factor VIII treatment. Reduced T helper:T suppressor/cytotoxic cell ratio can be caused by either decrease in the number of T helper cells or augmentation of the T suppressor/cytotoxic cell population. Lowered T helper:T suppressor/cytotoxic cell ratio does not, by itself, help to distinguish between AIDS and other causes of reduced ratios. Quantitative measurements are needed to define the T subset changes. AIDS is characterized by decrease in the number of T helper cells and reduced T helper:T suppressor/cytotoxic cell ratio. The T helper (Leu 3+) and T suppressor/cytotoxic (Leu 2+) cell subpopulations can change independently. Identification of decrease in the number of T helper cells as an alteration that occurs independently of numerical change in other lymphoid subpopulations, such as T suppressor/cytotoxic cells and B cells, and the close association of the decrease in the number of T helper cells with AIDS are consistent with a distinct pathogenesis (and cause) for AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Endolymphatic sac surgery in Mondini's dysplasia: a report of 16 cases.

This paper presents 12 patients (16 ears) with radiographic evidence of Mondini's dysplasia who underwent endolymphatic sac surgery. And additional 4 patients (7 ears) on whom surgery was not performed are included. Class I or II results were obtained in 81% of the ears. Pathophysiology, as it relates to the fluctuant nature of the hearing impairment, is discussed.

Adult↗
PubMed1984

Evidence for the presence of idiotype-bearing regulatory T cells in which idiotype expression does not show linkage to either IgH alleles or the MHC.

An anti-idiotypic antiserum was raised in rabbits to a monoclonal antibody with specificity for one of the two antigenic determinants on the ferredoxin (Fd) molecule. The monoclonal antibody (Fd-B2) was derived from fusion of spleen cells from Fd-immune B10.BR (H-2k, Ighb). Examination of an extensive number of samples of Fd-immune serum from B10.BR and other mouse strains established that the Fd-B2 idiotype is essentially never present in such sera in detectable concentrations (greater than 30 ng/ml). Administration of the anti-idiotypic antibody (anti-Fd-B2) i.v. to B10.BR mice, or treatment of B10.BR T cell-enriched populations with anti-Fd-B2 + C prior to adoptive transfer to irradiated B10.BR recipients followed by challenge with Fd resulted in a significant increase in the production of anti-Fd antibodies. This effect was specific and was not reflected by a change in expression of the Fd-B2 idiotype in the antibody produced. Similarly, injection of 10 micrograms of Fd-B2 into B10.BR mice resulted in an enhanced anti-Fd response. When similar experiments were carried out using B10.D2 mice (H-2d, Ighb), which are genetic non-responders to Fd, it was observed that treatment which anti-Fd-B2 followed by challenge with Fd resulted in production in treated animals of significant levels of antibody to Fd. Again, the antisera thus produced did not contain detectable levels of the Fd-B2 idiotype. Further experiments using high responder (H-2k) mice with Igh allotypes differing from the B10 strains (C57/BR, Igha, and RF/J, Ighc), showed that treatment of these animals with anti-Fd-B2 also resulted in a highly significant enhancement of the anti-Fd response. These data imply that the anti-idiotypic antiserum (anti-Fd-2B) is exerting its influence by acting on an id + population of T cells and that the expression of this id is not dependent on genetic linkage to either the H-2 or the Igh loci.

Animals↗
PubMed1983

Identification of an idiotypic marker of a major regulatory T cell of the immune response in B10.BR mice to ferredoxin. The relationship of idiotypic regulation to conventional hapten-carrier effects.

An anti-idiotypic antiserum was raised in rabbits to a monoclonal antibody (Fd-1) with specificity for one (the N epitope) of the two antigenic epitopes found on the ferredoxin (Fd) molecule. The anti-idiotypic antiserum (anti-Fd-1) was used to demonstrate that the Fd-1 idiotype was expressed at significant levels in most anti-Fd antisera raised in B10.BR mice. Examination of antisera raised in other mouse strains demonstrated that expression of this idiotype mapped to the IgH gene complex and was found in the antisera of all mouse strains examined with the Ig-1 allotype. When splenocytes from Fd-immune B10.Br mice were treated with anti-Fd-1 and transferred to irradiated syngeneic recipients, the adoptive secondary response was significantly higher in animals receiving treated cells as opposed to control animals, which received normal rabbit serum-treated cells. This response produced a net increase in antibody to both determinants, and the relative amount of Fd-1 idiotype was not significantly altered. Further studies with separated cell populations showed that the overall increase of anti-Fd antibody produced was attributable to the effects of the anti-idiotypic serum on a population(s) of T cells. Treatment of mice with the Fd-1 monoclonal antibody (which should react with anti-idiotypic cells) had an analogous effect to that of the anti-idiotype, in that mice so treated produced higher concentrations of anti-Fd antibodies when they were immunized and these antibodies exhibited net increases to both determinants. A model is presented to explain these results.

Amino Acid Sequence↗
PubMed1982

The use of unideterminant fragments of ferredoxin in the genetic mapping of determinant specificity of the immune response.

The ferredoxin (Fd) molecule is a small non-mammalian immunogenic protein containing 55 amino acid residues with only two major antigenic determinants located with the NH2-terminal heptapeptide and the COOH-terminal pentapeptide. Selective enzyme cleavages of Fd with either trypsin or carboxypeptidase A result in the inactivation of the antigenic determinants by the removal of a tripeptide at the NH2-terminal and two amino acid residues at the COOH-terminal, effectively leaving 52 and 53 amino acid fragments respectively, each containing a single antigenic determinant. Fd digested with both enzymes yielded a 50 amino acid peptide with both determinants inactivated. Purity of these digests was assessed using monoclonal antibodies in standard and antigen-blocking ELISAs. The doubly digested peptide had virtually no reactivity with anti-Fd sera, reconfirming that the central cysteine-rich region is serologically silent. It was found that the sum of the reactivities of the N- and C-determinant-bearing peptides as equal to that of the native Fd and that the ratio of the reactivities could be used to assess determinant selectivity in the response to Fd in congenic recombinant strains of mice. This method was used in mapping the determinant selectivity in the antibody response to the MHC of mice to the left of the I-B subregion. Use of the B10.HTT strain indicated that separate genes mapping to the same subregion code for the magnitude of the antibody response and the determinant selectivity of the response.

Amino Acid Sequence↗
PubMed1978

The localization within plant cells of enzymes involved in arginine biosynthesis.

Studies were carried out to determine the distribution of the following: (1) carbamoyl phosphate synthetase (EC 2.7.2.9), (2) ornithine carbamoyltransferase (EC 2.1.3.3), (3) argininosuccinate synthetase (EC 6.3.4.5), and (4) argininosuccinate lyase (EC 4.3.2.1) in soybean cells grown in suspension culture. Protoplasts were produced from the soybean cells by treatment with cellulase (EC 3.2.1.4) and pectinase (EC 3.2.1.15); the protoplasts were then ruptured by osmotic shock with distilled water. This treatment was followed by differential centrifugation and sucrose density gradient centrifugation to isolate various organelle fractions including mitochondria and plastids. Examination of these fractions using specific enzyme assays showed that carbamoylphosphate synthetase and ornithine carbamoyltransferase were localized in a fraction found to be composed primarily of plastids. Argininosuccinate synthetase and argininosuccinate lyase appeared to be associated with either the cytosol or a membrane fraction in close association with the cytosol such as the endoplasmic reticulum or protoplast membrane.

Arginine↗
PubMed1974

Effects of circulating red cell mass on diet-induced atrial thrombosis in mice.

Atrial thrombosis is a common lesion in female Taconic Swiss mice fed a high-fat (28%), low-protein (8%), hypolipotropic diet for 10 wk or longer. After the third week of such feeding the mice studied here were injected with either erythropoietin, washed, packed red blood cells, lysed red blood cells, plasma or physiological saline.In mice receiving injections of lysed red cells, plasma or saline, respectively 75, 54 and 82% of those surviving for 10 wk had developed atrial thrombosis. Hematocrits were 9.3% or below in these groups. Hematocrits were maintained at an average of 33.0% in the erythropoietin group and 32.4% in the transfused (packed erythrocytes) group. Only one of the erythropoietin injected animals and none of the transfused animals developed atrial thrombosis. The evidence indicates that the anemia induced by the experimental diet results from lack of erythropoietin production or activity and that the hypoxia of anemia plays a role in the development of atrial thrombosis.

Anemia↗