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Biomedical subjects

C I Smith

Publications and source records attributed to C I Smith.

At least 271 records · Page 15Linked to original sources

Acute Dane particle suppression with recombinant leukocyte A interferon in chronic hepatitis B virus infection.

The clinical, virologic, biochemical, and immunologic effects of a biosynthetic human leukocyte interferon, recombinant leukocyte A interferon (rIFN-A or HuIFN-alpha 2) are reported in nine patients with chronic hepatitis B virus infection and circulating Dane particle-associated polymerase activity. Eight-day courses of rIFN-A were given starting at a dose of 3 X 10(6) units per day and reaching 68 X 10(6) units per day in two patients. Major toxic side effects included fever, fatigue, gastrointestinal symptoms, myalgias, and headache. Most courses of rIFN-A were associated with a reduction in Dane particle-associated polymerase activity, but in no case was this change permanent. There were also changes in lymphocyte subpopulations at the higher dosage levels of rIFN-A. Because of the reproducible, statistically significant effect on viral replication, further study with this and other biosynthetic interferon species is warranted.

Adult↗

Mitogen-induced switching of immunoglobulin heavy-chain class secretion in chronic B-lymphocytic leukaemia and immunocytoma cell populations.

Lymphocytes from peripheral blood, bone marrow, and lymph nodes from six patients with chronic B-lymphoproliferative disease were studied. Two of the patients had a polymorphic immunocytoma with surface membrane immunoglobulin phenotype mu kappa. Four patients had chronic B-lymphocytic leukaemia (CLL) with the phenotypes mu kappa, mu delta kappa, mu lambda, and mu delta lambda, respectively. In no case did the monoclonal cell populations express gamma chains on the surface, and none produced monoclonal immunoglobulin in vivo. The malignant B lymphocytes were cultured in the presence of polyclonal B-cell activators. Immunoglobulin secretion was detected with the protein A plaque assay and with a modification of the reversed haemolysis-in-agar plaque assay. Immunoglobulin secretion was induced in four of the cell populations. In both the immunocytomas and in one of the CLL cell clones the heat-inactivated Staphylococcus aureus strain Cowan I induced secretion of IgG, as well as IgM, associated only with the same light chain as was expressed on the surface of the unstimulated cells. Thus, mitogens can induce immunoglobulin secretion in vitro in malignant B lymphocytes, and Cowan I bacteria also have the ability to induce a switch of immunoglobulin production from IgM to IgG in a fraction of the leukaemic cell populations.

Adult↗

Anti-IgA in selective IgA deficiency. In vitro effects and Ig subclass pattern of human anti-IgA.

Anti-IgA antibodies were found in 14 of 33 (42%) IgA-deficient donors. In healthy IgA-deficient blood donors anti-IgA appeared associated with the presence of HLA DR3. The antibodies were mainly of the IgG1 and, in high-titred sera, IgG4 subclasses. Sera containing high-titred anti-IgA selectively impaired IgA synthesis in vitro as induced by direct and indirect polyclonal B-cell activators. These antibodies may play a role in the pathogenesis and/or the maintenance of IgA deficiency.

Antibodies, Anti-Idiotypic↗

Gm allotypes in Swedish myasthenia gravis patients.

Gm phenotype frequencies were examined in 112 Swedish myasthenia gravis patients. The G1m 1,2,3 phenotype frequency in the total patient material did not differ significantly from that found in the normal population. However, when patients were subdivided, three different patient groups were observed with regard to Gm1 frequency: (1) Thymoma patients having a low frequency of Gm1, (2) Non-thymoma patients with a mild disease having a low frequency of Gm1 and (3) Non-thymoma patients with a severe disease having a high frequency of Gm1. When patients were subdivided according to presence or absence of HLA-B8 and Gm1 respectively, severe symptoms were less frequent in the HLA-B8+, Gm(-1) group as compared to the HLA-B8+, Gm(+1) group. Furthermore, there was an increased frequency of sera with anti-immunoglobulins not inhibitable by pooled control immunoglobulins.

Antibodies, Anti-Idiotypic↗

Virus-specific antibody activity of different subclasses of immunoglobulins G and A in cytomegalovirus infections.

Healthy donors and patients with primary or reactivated cytomegalovirus infections were examined for antiviral antibodies of the immunoglobulin G (IgG) and IgA subclasses. For this purpose, monoclonal antibodies against the four IgG and the two IgA subclasses were used in enzyme-linked immunosorbent assays with cytomegalovirus antigen. IgG1 and IgG3 were the principal anti-cytomegalovirus subclasses in serum samples from healthy donors and patients. IgG1 was higher in reactivated than in primary disease. Cytomegalovirus-specific IgG2 was detected only in serum samples with high total cytomegalovirus IgG. A few patients with high total serum IgG4 also had cytomegalovirus-specific IgG4 antibodies. During convalescence, there was no significant increase in total IgG of any subclass. Both IgA1 and IgA2 antibodies with cytomegalovirus specificity were detected in patients who had cytomegalovirus antibodies of the IgA class.

Antibodies, Viral↗

Role of penicillamine for the induction of myasthenia gravis.

Penicillamine and derivatives of this drug were tested for lymphocyte-activating properties. D- as well as L-penicillamine induced in vitro DNA synthesis in mouse splenocytes, whereas D-penicillamine methyl ester, N-acetyl-D-penicillamine and D-penicillamine disulfide were devoid of stimulatory properties. Lymphocytes from athymic mice were also responsive. However, we were unable to detect an increased antibody secretion in mouse spleen cell cultures exposed to penicillamine. Human peripheral blood lymphocytes from healthy individuals as well as from patients with penicillamine-induced myasthenia gravis only gave minor proliferative responses after in vitro penicillamine exposure. Furthermore, there were no differences in proliferative capacity between these two groups. Cultivated human peripheral blood or spleen cells were not activated to antibody secretion in the presence of penicillamine. There were no signs of myasthenia gravis using single-fiber electromyography recordings in patients with rheumatoid arthritis being on penicillamine treatment or in mice from several different mouse strains receiving penicillamine in their drinking water. However, NZB/NZW hybrid mice receiving penicillamine had increased amounts of antinuclear and anti-dsDNA antibodies.

Animals↗

IgG2 deficiency in a healthy blood donor. Concomitant lack of IgG2, IgA and IgE immunoglobulins and specific anti-carbohydrate antibodies.

Lack of serum IgG2, IgA and IgE was found in a healthy male adult blood donor. No secretory IgA could be demonstrated. In vitro activation of lymphocytes did not induce IgA secreting cells although no class specific suppressor cells could be found. Normal or slightly subnormal titres to a variety of bacterial and viral antigens were demonstrated whereas anti-carbohydrate antibodies (anti-teichoic acid, anti-dextran and anti-pneumococcal polysaccharide) were virtually absent. Isoagglutinins and heteroagglutinins were present in somewhat lower concentrations than normal.

Adult↗

Functional maturity of cord blood B lymphocytes: Staphylococcus aureus Cowan 1 induces IgG secretion in the human neonate.

Lymphocytes from newborn infants and adults were investigated with the polyclonal B cell activators Staphylococcus aureus Cowan 1, soluble protein A, and pokeweed mitogen (PWM). In cord blood lymphocytes (CBL), protein A and PWM induced only meagre IgM responses, whereas Cowan 1 bacteria induced synthesis of both IgM and IgG in quantities comparable to adult levels. We were also able to establish the neonatal origin of the Ig producing cells. Thus, cord blood lymphocytes seem to be functionally mature enough to produce any Ig class, provided they are given the right stimulus.

Adult↗

Human leukocyte antigens group A in couples with unexplained infertility.

The human leukocyte antigen (HLA) frequencies and antigen sharing were studied in 14 couples with unexplained infertility. There were no significant differences in the frequency of HLA-A, B, C, or DR antigens, as compared with normal control subjects. Furthermore, the degree of HLA sharing did not deviate from that theoretically expected. An increased frequency of HLA-DR sharing, as compared with the expected frequency, was observed in a control group consisting of parents of children with leukemia. When infertile spouses were tested for mixed lymphocyte culture reactivity, there were no indications of an altered reactivity, as compared with control subjects.

Female↗

Preliminary studies of acyclovir in chronic hepatitis B.

Three patients with HBsAg-positive and DNA-polymerase-positive chronic hepatitis were treated with increasing dosages of intravenous acyclovir. A fall in DNA polymerase activity was seen with all courses of acyclovir but no dose-response relationship was evident. In only one patient did DNA polymerase fall to zero where it has remained for five months. Two out of 10 courses were associated with significant side effects with the highest dosages of acyclovir but these promptly resolved when the agent was stopped. Acyclovir's apparently partial and transient action suggests that it will not have a role in the treatment of chronic hepatitis B virus infection.

Acyclovir↗

Vidarabine monophosphate and human leukocyte interferon in chronic hepatitis B infection.

Ten young adult patients with chronic hepatitis B virus infection and positive hepatitis B e antigen and DNA polymerase (DNAP) levels were treated with alternating courses of seven to 28 days of 5 to 7.5 mg/kg of vidarabine monophosphate (adenine arabinoside monophosphate) and 28 days of human leukocyte interferon (IFN-alpha); three different regimens were given on an outpatient basis. All patients with a fall in their DNAP level, and the DNAP remained undetectable six months after treatment was stopped in one patient. The major side effect, which most often occurred in those patients receiving 7.5 mg/kg of vidarabine monophosphate, was severe muscular pains. This study demonstrated the feasibility of administering vidarabine monophosphate and interferon to outpatients. Based on data from this and other studies, it is now possible to use a relatively nontoxic regimen that includes 28 days of 5 mg/kg of vidarabine monophosphate in a larger controlled study to answer the question of efficacy.

Adult↗

Binding and incorporation of lecithin-cholesterol vesicles to lymphocytes: a spin-label study.

When lecithin-cholesterol vesicles, containing the membrane-bound spin probe 3-doxyl-cholestane, were set in contact with mouse lymphocytes, the vesicles adsorbed to the cell and vesicle-membrane components were transferred to it. The spin probe was enzymatically reduced at the inside of the cell membrane. The spin-label method provided a means to determine quantitatively the extent of vesicles adsorption and vesicle-cell fusion by measuring the transfer of vesicles membrane material to the cell. This method, together with the reduction of spin label by the cell, allowed also a quantitative estimate to the extent of endocytosis during cell-liposome interaction.

Animals↗

Sex-dependent induction of human suppressor T cells by chorionic gonadotropin.

Human chorionic gonadotropin (hCG) in physiological retroplacental concentration has been shown to induce human female lymphocytes which suppress the proliferation and differentiation of B cells stimulated by purified protein derivative of tuberculin. To test whether the hCG-induced suppression was sex dependent parallel experiments using female and male peripheral lymphocytes were performed. hCG did not induce cells capable of suppressing purified protein derivative induced B cell proliferation in lymphocytes from males, which was in contrast to lymphocytes from females where a statistically significant suppression was found. A similar hCG-induced suppressive effect was found before menarche, after the menopause and in two patients with Turner's syndrome, suggesting that a gene(s) on the Y chromosome exerts a regulatory function and thus prevents the hormone from inducing suppressor T cells.

Aging↗

Evidence for a spontaneous activity and a weak helper function in cord blood lymphocytes.

Human lymphocytes from cord blood (CBL) and adult peripheral blood were studied for suppressive and stimulatory effects. Using a double chamber assay we found that via soluble substance(s) cells from approximately 90% of all cord bloods and about 25% of the tested adults could diminish the proliferative response and the IgM and IgG plaque-forming cell numbers of phytohemagglutinin (PHA) stimulated adult cell cultures. CBL were spontaneously suppressive, whereas cells from 'suppressive adults' required activation with PHA to exert suppression. Co-cultures of T cells and B cells were stimulated with pokeweed mitogen. Cord B lymphocytes were able to secrete not only IgM but also IgG. The Ig response of CBL was weaker than that of adult cells, which argues for an immaturity of cord helper T lymphocytes, and possibly also of cord B lymphocytes.

Female↗