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Biomedical subjects

A Rubinstein

Publications and source records attributed to A Rubinstein.

At least 271 records · Page 15Linked to original sources

A case of lymphogranuloma venereum of 20 years' duration. Isolation of Chlamydia trachomatis from perianal lesions.

Chlamydia trachomatis was isolated from perianal lesions in a patient in whom lymphogranuloma venereum had been diagnosed 20 years previously. Treatment with tetracycline resulted in a pronounced improvement. Although C trachomatis is known to persist for a long time in the host, isolation of the micro-organism from infected tissues after such a prolonged period has not previously been reported.

Aged↗

Plasma deoxyadenosine, adenosine, and erythrocyte deoxyATP are elevated at birth in an adenosine deaminase-deficient child.

We have determined concentrations of adenosine, deoxyadenosine, and deoxyATP (dATP) in cord blood from an infant prenatally diagnosed as ADA deficient. Plasma deoxyadenosine and adenosine were already elevated in cord blood (0.7 and 0.5 microM vs. normal of less than 0.07 microM). Elevation of plasma deoxyadenosine has not previously been documented in these children. Erythrocyte dATP content was also elevated at birth (215 nmol/ml packed erythrocytes vs. normal of 2.9). These elevated concentrations of adenosine, deoxyadenosine, and dATP are similar to those we observed in another older adenosine deaminase-deficient patient and may explain the impaired immune function and lymphopenia seen at birth.

Adenosine↗

Abnormalities of immunoregulatory T cells in disorders of immune function.

We studied a five-year-old girl with several autoimmune disorders and a 16-year-old boy with acquired agammaglobulinemia to determine whether aberrations of immunoregulatory T cells could explain some instances of immunodeficiency or autoimmunity. The normal peripheral blood T-cell population, as defined by specific heteroantiserums, is 20 per cent TH2+ and 80 per cent TH2-. Human suppressor cells are TH2+, whereas helper cells are TH2-. In addition, each subset expresses Ia antigens upon activation. Our patient with autoimmune disease had no demonstrable TH2+ cells, and her lymphocytes could not be induced to suppress. Her circulating T cells were of an activated-helper phenotype, i.e., TH2-,Ia+. In contrast, in the boy with agammaglobulinemia, the T-cell population was predominantly of an activated-suppressor phenotype, i.e., TH2+,Ia+. This patient's T cells abrogated both his own and his histoidentical brother's B-cell secretion of immunoglobulins. We conclude that the characterization of T cells may provide insight into the causes of a number of abnormal immune states in man.

Adolescent↗

In vivo and in vitro effects of thymosin and adenosine deaminase on adenosine-deaminase-deficient lymphocytes.

Two siblings with adenosine deaminase deficiency were studied before and during "enzyme replacement" therapy (partial exchange transfusions with normal red cells containing the missing enzyme). The younger sib showed improvement of immunologic function during red-cell therapy alone, whereas in the older sib this improvement occurred only when the transfusions were supplemented by thymosin injections. Their clinical courses correlated with in vitro findings: lymphocytes from the younger sib differentiated to T-cell-rosette-forming cells upon addition of adenosine deaminase alone; lymphocytes from the older sibling required supplemental thymosin to form these cells. Thymic factors appear to influence the response to transfusion therapy in some patients deficient in adenosine deaminase, and supplementation of red-cell transfusion with thymic factors may be required.

Adenosine Deaminase↗

Possible nonspecific immunopotentiation by 2,4-dinitrochlorobenzene sensitization in patients with Hodgkin's disease.

Various immunological parameters were evaluated in untreated Hodgkin's patients before and after sensitization with dinitrochlorobenzene (DNCB). The ratio (r) of these parameters after/before DNCB sensitization for patients and second/first samples in the controls were calculated. There were significantly more patients in the r greater than 1.1 group for PHA and Con A responses and for peripheral blood T cell percentages. These data suggest that DNCB sensitization may have a nonspecific immunopotentiation effect.

Antibody Formation↗

Mutagen-induced disturbances in the DNA of human lymphocytes detected by antinucleoside antibodies.

The alkylating mutagens N-methyl-N'-nitro-N-nitrosoguanidine, methyl methanesulfonate, and N-nitroso-methylurea induced immunoreactivity to antinucleoside antibodies in human peripheral blood lymphocytes in vitro. This could also be detected in lymphocytes taken from a patient soon after i.v. administration of cyclophosphamide. The immunoreactivity response, which indicates denatured DNA or DNA single-strand breaks, was scored by immunofluorescent or immunoperoxidase techniques. Examination of blood from 10 normal subjects showed that 32 +/- 4% (S.E.) of resting peripheral blood lymphocytes were immunoreactive to antinucleoside antibodies. We have shown that these naturally occurring immunoreactive lymphocytes are largely accounted for by a subpopulation of thymus-derived lymphocytes bearing the Fc receptor for immunoglobulin M. The presence of these cells did not interfere with the use of peripheral blood lymphocytes for in vitro measurement of additional immunoreactivity caused by alkylating mutagens. The response proved to be dose dependent; up to 90% of lymphocytes could be rendered immunoreactive. Parallel studies with HeLa cells showed a similar dose-response relationship between mutagen action and immunoreactivity. With some agents, the immunoreactivity technique detected effects at lower concentrations than could be detected by HeLa cell survival studies. With N-nitrosomethylurea, measurement of DNA repair synthesis by [3H]thymidine autoradiography showed that in HeLa cells these two parameters of response to DNA damage increased in parallel. Our results provide a new basis for detecting the action of alkylating mutagens on human lymphocytes in vitro or in vivo.

Alkylating Agents↗

Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency.

The inherited deficiency of adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) activity in humans is associated with an immunodeficiency. Some of the immunodeficient and enzyme-deficient patients respond immunologically to periodic infusions of irradiated erythrocytes containing adenosine deaminase. It has been previously reported that erythrocytes and lymphocytes from immunodeficient ane enzyme-deficient children contained increased concentrations of ATP, and in the one child studied after erythrocyte infusion therapy, the intracellular level of ATP diminished. Using high-pressure liquid chromatography that resolves ATP and 2'-dATP, we have observed greater than 50-fold elevations of dATP in the erythrocytes of immunodeficient, adenosine deaminase-deficient patients but not in the erythrocytes of an immunocompetent adenosine deaminase-deficient patient. The erythrocyte dATP in two unrelated adenosine deaminase-deficient, immunodeficient patients disappeared after infusion of normal erythrocytes. We propose that deoxyadenosine, a substrate of adenosine deaminase, is the potentially toxic substrate in adenosine deaminase deficiency, and that the mediator of the toxic effect is dATP, a recognized potent inhibitor of ribonucleotide reductase.

Adenine↗

Impairment of cell-mediated immunity in ectodermal dysplasia with aplastic anemia.

A case of ectodermal dysplasia and aplastic anemia is presented in which a cell-mediated immunodeficiency led to a fatal Pneumocystis carinii infection. Elevated levels of IgG, IgA and IgD were present with normal specific antibody titres. A deficient cell-mediated immunity was documented by low T cell numbers, poor in vitro mitogenic responses, negative skin tests and by the histologic finding at autopsy of thymic dysplasia.

Anemia, Aplastic↗

Comparative analysis of systemic immunological parameters in ulcerative colitis and idiopathic proctitis: effects of sulfasalazine in vivo and in vitro.

Comparative analysis of the systemic immunity revealed similarities between ulcerative colitis and idiopathic proctitis. In the active stage of both diseases, circulating complement receptor positive cells were increased whereas T-cell percentages and lymphocyte functions were decreased. In severe forms of ulcerative colitis and idiopathic proctitis circulating EAC-phagocytosing esterase positive cells, indicative of activated monocytes, were demonstrated. Successful treatment with salicylazosulfapyridine (SASP) reversed these immunological changes. Incubation of SASP and its metabolites with leucocytes from patients and control subjects, in concentrations similar to those demonstrated in sera from patients treated with SASP, did not alter the immunological changes.

Adult↗

Immunohistochemical changes in morphologically involved and uninvolved colonic mucosa of patients with idiopathic proctitis.

Alterations in secretory component, IgA, IgG, and IgM were studied by immunofluorescent techniques in mucosal biopsy specimens obtained at colonoscopy from inflamed and grossly uninvolved colonic mucosa from 12 patients with idiopathic proctitis. Parotid-salivary secretory component and IgA and serum immunoglobulins were also investigated. Decreased secretory IgA was observed in the epithelium of all grossly involved rectal mucosa and in 40% of proximal normal mucosa. Salivary secretory IgA was not diminished. These observations suggest that a local immune defect may be pathogenetically related to idiopathic proctitis.

Adult↗