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Biomedical subjects

T H The

Publications and source records attributed to T H The.

At least 235 records · Page 13Linked to original sources

Systemic involvement and immunologic findings in patients presenting with Raynaud's phenomenon.

Systemic involvement and spectrum of autoantibodies were evaluated in 91 patients presenting with Raynaud's phenomenon. Decreased pulmonary diffusing capacity was observed in 23 percent, esophageal hypomotility in 14 percent and renal involvement in 5 percent of the patients, all without clinical symptoms. Arthralgia or a history of arthritis was present in 27 percent and skin abnormalities in 30 percent. Extent of systemic involvement was correlated with the severity of Raynaud's phenomenon, as measured by photoelectric plethysmography (r = 0.38; p < 0.01). In addition, both the variety of different autoantibodies in the serum of individual patients and the titer of antinuclear antibodies were positively correlated with the number of affected organ systems (r = 0.63; p < 0.01 and r = 0.65; p < 0.01, respectively). Raynaud's phenomenon is an important clinical sign of asymptomatic systemic disease. Measurements of its severity and serologic parameters are helpful in predicting the extent of systemic involvement.

Adult↗

Immune reactivity of women on hormonal contraceptives. Phytohemagglutinin and concanavalin-A induced lymphocyte response.

To investigate the influence of sex-steroids on the in vitro correlate of cell-mediated immunity (CMI), blood samples from 49 women on hormonal contraceptives were tested on the lymphocyte response to the mitogens phytohemagglutinin (PHA) and concanavalin A (Con-A). Sixteen women were taking oral contraceptives of combined oestrogen/progestogen of the same brand (low oestrogenic and middle range progestogenic activity); 15 had received intramuscular injections of medroxyprogesterone acetate and 18 women were using a sequential pill. The results were compared with those of 18 women not taking contraceptive steroids and matched for age. No significant changes were observed between the different groups. Considering the previously found alterations in dinitrochlorobenzene (DNCB) skin test reactivity by sex steroids, it is hypothesized that sex-steroids have little or no influence on the central proliferative phase of the immune response, but have a profound effect on the efferent phase.

Adolescent↗

Lymphocyte reactivity in infectious mononucleosis.

Reactivity of lymphocytes to a purified preparation of Epstein-Barr virus (EBV) was studied in 17 healthy individuals and 15 patients with primary EVB infection and clinical signs of infectious mononucleosis. Lymphocyte reactivity to EBV was negative in individuals who were seronegative for antibody to EBV and in seven of 15 patients examined less than or equal to 21 days after onset of clinical signs of illness. Positive lymphocyte reactivity was observed in all patients by day 36; once it was established, it remained in individual patients for up to 480 days. During the acute phase of infectious mononucleosis, negative lymphocyte reactivity was always associated with a strong antibody response to EBV capsid antigens. This disparity was paralleled by the inability of lymphocytes to respond to recall antigens and mitogens, especially concanavalin A. Positive lymphocyte reactivity to EBV indicates a specific cellular memory function, probably of thymus-cell origin, which is acquired following primary EBV infection, and may be retained into later life.

Adolescent↗

High immune responsiveness in a family with multiple paraproteinaemia and autoimmune thyroid disease.

Immune responsiveness was investigated in a family comprising 12 first- and second-degree relatives, one of whom had kappa-myelomatosis, one IgA-lambda paraproteinaemia, two Graves' disease and a further two thyroid antibodies without disease. Relatives by marriage served as controls. Parameters of immune capacity studied were the humoral and cellular immune response to haemocyanin of Helix pomatia (HPH), dinitrochlorobenzene (DNCB) skin reactivity and in vitro lymphocyte proliferation capacity to phytohaemagglutinin (PHA). Mean antibody titres to HPH were higher in the family than in the control group in all main Ig classes and IgG subclasses after primary and secondary immunization, and the difference was statistically significant for IgG, IgG2 and IgG4 titres. This could not have been predicted from the (normal) serum Ig levels in this family. In vitro lymphocyte proliferation capacity to HPH after primary and secondary immunization was also significantly increased. DNCB skin reactivity also tended to be high in the family, whereas PHA-induced lymphocyte proliferation was normal. These findings support the idea that myelomatosis clusters in families with immune dysregulation.

Adult↗

HLA-B8 in Raynaud's phenomenon.

A study of the distribution of histocompatibility (HLA) antigens in patients with Raynaud's phenomenon (RP) is presented, based upon the analysis of RP patients with and without connective tissue disease (CTD). In all patients, the phenomenon preceded the other symptoms of CTD by several years. The RP patients with CTD showed a significantly increased frequency (59%) of HLA-B8 compared with the frequency (23%) of that same antigen in the Dutch population. The RP patients without CTD showed no significant difference in frequency of HLA-B8. At least 50% of the patients with RP and HLA-B8 develop a CTD versus 18% of the patients without HLA-B8. It is suggested that HLA testing in patients with isolated RP may help to distinguish the patient in whom RP is the first symptom of CTD from the patient with truly primary RP.

Adult↗

Comparison of in vitro lymphocyte proliferations induced by cytomegalovirus-infected human fibroblasts and cell-free cytomegalovirus.

In vitro lymphocyte reactivity (LR) to cytomegalovirus (CMV)-infected human fetal fibroblasts (CMVFF) and cell-free CMV were measured by using lymphocytes from healthy donors. Lymphocytes from all seropositive donors were stimulated by CMVFF, whereas lymphocytes from negative donors were not. The optimal stimulator cell-to-lymphocyte ratio was in the range of 1:5 to 1:50, dependent on the virus dose used. LR to cell-free CMV was positive for 15 out of 18 seropositive donors and negative for 14 out of 16 seronegative donors. In most cases LR to CMVFF was considerably higher than LR to cell-free CMV. Within the CMV seropositive group there was no significant correlation between the LR to either CMVFF or cell-free CMV and the levels of antibodies to CMV early antigens or CMV late antigens. There was no strict correlation between LR to CMVFF and to cell-free CMV, especially not in tests with lymphocytes from two patients with CMV mononucleosis. Our data suggest that CMVFF and cell-free CMV are recognized (partly) by different subpopulations of CMV-specific memory lymphocytes. We conclude that the use of CMV-infected cells, in addition to cell-free CMV, in LR tests gives more reproducible and possibly also additional information about CMV-specific cellular immunity.

Antibodies, Viral↗

Adjuvant immunotherapy with BCG in squamous cell bronchial carcinoma.

Fifty-four patients with evidence of locally advanced primary squamous cell bronchial carcinoma (SCC), and three patients with adenocarcinoma (AC) had lung resection to remove all the visible tumour. After operation an randomly chosen group of 20 SCC patients received adjuvant BCG immunostimulation by scarifications (BCG-A). An additional group of 14 SCC patients, and three AC patients received initially intrapleural BCG treatment and subsequently scarifications (BCG-B). A control group of 20 SCC patients received no adjuvant treatment. Follow-up studies were done from three to 51 months. Immune reactivity was monitored in vivo with PPD skin tests in 33 treated and in 18 untreated patients. In both the BCG-treated SCC groups recurrence rates decreased statistically significant during follow-up (BCG-A; six to 51 months, p less than 0.001; BCG: 6-9 months, p less than 0.01 and nine to 24 months, p less than 0.001). However, no difference could be demonstrated between systemic and combined systemic and intrapleural treatment. The three BCG-treated AC patients all relapsed within nine months of follow-up. A pronounced increase in skin reactivity to PPD was seen six months after surgery in the BCG-treated patients (BCG-A, p less than 0.001; BCG-B, p less than 0.01), whereas the control patients remained anergic after surgery. This improved immune reactivity went in parallel with a more favourable outcome of the individual patients (BCG-A, p less than 0.02; BCG-B, p less than 0.05). It is concluded that adjuvant BCG immunotherapy used in strongly selected patients with minimal residual squamous cell bronchial carcinoma improves the prognosis. Intrapleural treatment did not improve the prognosis further. A favourable clinical outcome was mirrored by an increase in cellular immune reactivity.

Adenocarcinoma↗

Defective stimulating capacity of leukocytes in mixed leukocyte culture in constitutional aplastic anemia caused by suppressor T cells. A case study.

A patient with constitutional Fanconi-like aplastic anemia who developed a preleukemic state was transplanted with bone marrow from his HLA-identical MLC-negative brother. Before transplantation his mononuclear leukocytes were found to have a defective stimulating and responder capacity in mixed leukocyte culture with cells of an unrelated individual. After removal of T cells the stimulating capacity was completely restored. MLC testing with separated cell fractions seems important to establish HLA-D identity with a possible donor, especially when MLC tests with unseparated cells are negative.

Adult↗

Cytomegalovirus-specific immune response and the cellular immune status of malignant lymphoma.

Cytomegalovirus (CMV)-specific immune responses and the general cellular immune status of 24 untreated patients with Hodgkin's disease (HD) and 22 with non-Hodgkin lymphoma (NHL) were evaluated in comparison with matched controls. The incidence of antibodies against CMV-induced early (EA) or late (LA) antigens was not different between patients and controls. LA antibody titres were markedly lower in the lymphoma patients (p = 0.01), especially in the NHL subgroup (p = 0.008), but not in HD patients. EA antibody titre levels were not significantly different between patients and controls. CMV-specific lymphocyte reactivity (LR) was impaired in LA seropositive--and even more so in EA seropositive--lymphoma patients. General cellular immunity tested with LR to mitogens and an antigen cocktail was more disturbed in HD patients (only PWM-LR normal) than in NHL patients (only Con A-LR disturbed). The percentage of circulating T lymphocytes was markedly lowered (less than 60%) in only 2 HD and 4 NHL patients. The impairment of CMV-LR was not directly related to the general cellular immune status of the patients. It appeared furthermore to be virus-specific when it was compared with LR to Epstein-Barr virus antigen. The impairment of CMV-specific immunity in lymphoma patients probably reflects a defect of the immunological defence against endogenous CMV. This defect apparently, occurs early in the course of illness before the general cellular immune status has deteriorated and it may have a pathogenetic significance for lymphoid malignancies.

Adolescent↗

Suppression of DNA synthesis by con A-activated human lymphocytes: role of monocytes in con A-induced suppression.

Human peripheral blood mononuclear leucocytes, activated by Con A, suppress the antigen- or mitogen-induced proliferation of autologous responder cells. Generation of suppressor cells is prevented by mitomycin treatment before Con A activation. Once cells are activated, their suppressive activity is not affected by mitomycin treatment. Monocytes are not only required for generation of suppressor cells, but are also involved in suppression as effector cells. Monocyte-mediated suppression is blocked by indomethacin, suggesting that this suppression is mediated by prostaglandin. It is concluded that monocytes are involved in Con A-induced suppression of DNA synthesis.

Cell Division↗

Immune reactivity of women on hormonal contraceptives: dinitrochlorobenzene sensitization test and skin reactivity to irritants.

To evaluate the influence of sex steroids on immunity in 87 women on hormonal contraceptives, sensitization tests were performed with the contact allergen, 2,4-dinitrochlorobenzene (DNCB). Forty-five women were taking oral contraceptives of combined oestrogen/progestogen of the same brand (low oestrogenic and middle range progestogenic activity); 27 had received intramuscular injections of medroxyprogesterone acetate and 15 women were using a sequential pill. The results were compared with those of 44 women not taking contraceptive steroids and matched for age. In women on the combined pill and those who had received intramuscular progesterone, the mean DNCB reactivity was significantly increased (0.02 less than p less than 0.05 and 0.001 less than p less than 0.01, respectively), whereas women using a sequential pill proved to show a decreased skin reactivity in the oestrogenic phase of this pill. (p = 0.05). The changes observed proved to be specific, since no statistically significant differences in overall skin reactivity to irritants between the four groups of women could be observed. The clinical implications of these results have been considered.

Adolescent↗

Immune complexes in peripheral blood polymorphonuclear leucocytes of patients with Raynaud's phenomenon.

Phagocytosed immune complexes in polymorphonuclear (PMN) leucocytes of sixty-nine patients with Raynaud's phenomenon were studied by scoring the cells for IgG and complement inclusions. The results were compared with the degree of vasospasm, as measured by photoelectric plethysmography of the fingers after cooling. Median IgG and complement scores of PMN cells were significantly elevated in patients with Raynaud's phenomenon when compared with those of the control group (P less than 0.01). Patients with a positive (n = 35) or a strongly positive (n = 11) plethysmographic test showed significantly higher median IgG and complement scores than those with a negative plethysmorgraphic test (n = 23). They also showed elevated IgG and complement scores in a greater proportion (89 and 100%, respectively, vs 48%).Thus, a positive relationship was shown to exist between the degree of vasospasm and the levels of phagocytosed immune complexes in circulating PMN leucocytes. In secondary Raynaud's phenomenon high levels of phagocytosed immune complexes were found. In primary Raynaud's, patients with some clinical or laboratory signs of an auto-immune disease (n = 12), who were classified as "suspected secondary", had higher IgG and complement scores than those without such signs (n = 37). This suggests that the test for immune complex detection may distinguish patients with connective tissue disease-associated Raynaud's phenomenon from those with truly primary Raynaud's, in an early stage of the disease. The clinical and patho-physiological implications of these findings with regard to the Raynaud phenomenon are discussed.

Antigen-Antibody Complex↗

Class- and subclass-specific antibody response to hemocyanin in nonmalignant paraproteinemia.

IgM, IgG, and IgA class-specific, as well as IgG subclass-specific antibody titers against the primary immunogen HPH were measured with ELISA in 19 patients with nonmalignant paraproteinemia (eight with IgG1, two with IgG2, two with IgG4, four with IgM, and three with IgA) and in a simultaneously studied age- and sex-matched control group. After primary immunization only IgM and IgA anti-HPH titers were significantly lower in the patient group. Four patients with relatively high IgG or IgA serum paraprotein levels did not produce antibodies in some Ig classes or IgG subclasses, whereas all other patients and all controls developed antibody titers in all classes and IgG subclasses. Low or absent antibody titers did not occur preferentially in the Ig (sub)classes to which the paraproteins belonged. After secondary immunization the patients could not increase or maintain their antibody titers as well as the controls, and this was most clear in the IgM and IgA antibody class. A direct correlation between polyclonal serum IgM levels and IgM anti-HPH titers was present in the patients. Such a correlation was absent for IgA in the patients and for all classes in the controls. It is concluded that humoral immunosuppression as measured with a newly encountered antigen in patients with nonmalignant paraproteinemia is most clearly expressed in the IgM and IgA antibody class and that the paraprotein (sub)class is not preferentially involved.

Adult↗