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Biomedical subjects

C G Kallenberg

Publications and source records attributed to C G Kallenberg.

At least 235 records · Page 13Linked to original sources

Nifedipine in Raynaud's phenomenon: relationship between immediate, short term and longterm effects.

Sixteen patients with Raynaud's phenomenon (8 with primary Raynaud's, 8 with systemic sclerosis including 3 patients with CREST) were treated for 4 weeks in a double blind crossover study with nifedipine, 20 mg twice daily. Treatment resulted in improvement of symptoms (p less than 0.05), a lower frequency of attacks (p less than 0.05) and a tendency to a shorter duration of the attacks. Photoelectric plethysmography during nifedipine treatment showed greater amplitudes on cooling (p less than 0.05) and a better and faster recovery on rewarming (p less than 0.05) than during placebo. The immediate effect of nifedipine, 10 mg sublingually, on the amplitude of the plethysmogram, finger temperature, heart rate and blood pressure did not correlate with the effect of maintenance treatment. Dose titration based on therapeutic effect and side effects resulted in a dose of 20 mg daily for 5 patients, 40 mg for 7, and 80 mg daily for 3 patients. Longterm treatment (16-20 weeks) resulted in sustained efficacy, both by subjective and objective standards (plethysmography).

Adult↗

Expression of class II MHC antigens on alveolar epithelium in fibrosing alveolitis.

Lung biopsy specimens from eight patients with fibrosing alveolitis with or without connective tissue disease were investigated for the presence of immune deposits and the expression of class II histocompatibility antigens on the alveolar epithelium. Immune deposits were not detected. The alveolar epithelium stained strongly with anti-Ia (HLA-DR) monoclonal antibodies in seven out of eight biopsy specimens from the patients, but not in control lung tissue. Sub- and intra-epithelially localized mononuclear cell infiltrates consisted predominantly of T8-positive (cytotoxic/suppressor) lymphocytes. The expression of class II antigens on the alveolar epithelium and its infiltration with T8 positive cells is consistent with local presentation of self-antigens and an ensuing local immune response.

Adult↗

Sensitivity to hydrocortisone is a relevant factor in the immunoendocrine relationship. I. The cell-mediated immune response in relation to blood levels and in vitro immunosuppressive effects of hydrocortisone in patients with asthma and healthy control subjects.

The role of endogenous hydrocortisone in the regulation of lymphocyte activity was assayed in patients with asthma (patients with chronic nonspecific lung disease, characterized by attacks of dyspnea, alternating with symptom-free periods) and healthy control subjects. After priming, delayed-type hypersensitivity skin reactions were induced with Helix pomatia hemocyanin (HPH). Hydrocortisone blood levels were measured. The effect of hydrocortisone on HPH-induced lymphocyte proliferation was determined in vitro. The results demonstrate that hydrocortisone in low concentrations (100 ng/ml) inhibited in vitro lymphocyte proliferation equally in patients and control subjects. However, both groups demonstrated a large interindividual variation in hydrocortisone sensitivity. Therefore, in order to determine the immunologic effect of hydrocortisone blood levels in vivo, a hydrocortisone suppression index (HSI) was calculated by use of the information on hydrocortisone concentrations in vivo and the biologic effect of hydrocortisone in vitro. This HSI appeared to be inversely related with the in vivo cell-mediated immune response to HPH. This was reflected in an inverse correlation between HSI and delayed-type hypersensitivity skin reactions to HPH, both in patients (R = -0.64), in control subjects (R = -0.69), and in the total group (R = -0.68; p less than 0.001). No differences were observed between patients and control subjects. It is concluded that endogenous hydrocortisone is likely to play an important role in the regulation of lymphocyte activity in patients with asthma and healthy control subjects. This may have important consequences for the clinical expression of asthmatic symptoms, since the role of lymphocyte activity in the pathogenesis of asthma is increasingly recognized.

Adult↗

Primary cell-mediated immune response in bronchial asthma. Relationship between primary in vitro and in vivo cell-mediated and antibody responses in patients with asthma and healthy controls.

Eleven patients with asthma and ten sex and age matched healthy controls were immunized with the primary immunogen Helix pomatia Haemocyanin (HPH). The amplitude and the kinetics of in vitro cell-mediated immune response were measured by HPH-induced lymphocyte proliferation. Lymphocytes were also challenged in vitro with mitogens and recall antigens. In vivo cell-mediated immunity was determined by inducing delayed type hypersensitivity reactions with HPH. Anti-HPH antibody responses in the IgE, IgG and IgM classes were measured to gain an insight into the relation between cell-mediated and humoral immune responses in patients with asthma and healthy controls. The in vitro and in vivo cell-mediated response and the IgM antibody response did not differ between patients with asthma and controls. The IgE and IgG antibody responses, however, were increased in the patients. IgM antibody response correlated with both the in vitro and in vivo cell-mediated response (R = 0.45, P less than 0.05). IgE and IgG antibody responses however were not correlated with cell-mediated responses. These data suggest that the primary abnormality in immune regulation in patients with asthma concerns the control of the IgE and IgG class antibody responses.

Adult↗

Fluctuations in anti-nRNP levels in patients with mixed connective tissue disease are related to disease activity as part of a polyclonal B cell response.

In a follow up study of 11 patients with mixed connective tissue disease the levels of antibodies to nuclear ribonucleoprotein (nRNP) as measured by an enzyme linked immunosorbent assay (ELISA) were related to clinical activity of disease. To assess the relation between anti-nRNP levels and disease activity the levels of total immunoglobulin G, IgM rheumatoid factor (IgM RF), and antibodies to an unrelated antigen (tetanus toxoid) were determined simultaneously. No significant changes in anti-nRNP levels were noted in four patients with minor activity of disease. Major flares of disease were observed in seven patients. Clinical symptoms were preceded by a rise in anti-nRNP level in these patients unless they received immunosuppressive agents before the exacerbation. Conversely, when a rise in anti-nRNP level occurred a major flare of disease was followed in all but one case. Anti-nRNP levels fell during clinical improvement whether or not immunosuppressive treatment was given. All patients showed parallel fluctuations in anti-nRNP, IgM RF, and total immunoglobulin G levels. Furthermore, parallel fluctuations were seen in the levels of anti-nRNP and antibodies to tetanus toxoid except in one patient. We conclude that measurement of anti-nRNP by ELISA may be a guide for disease activity in connective tissue disease. Fluctuations of anti-nRNP are not restricted to this antibody, however, but are part of a more polyclonal activity of the B lymphocyte system.

Antibodies, Antinuclear↗

Epidermodysplasia verruciformis. Skin carcinoma containing human papillomavirus type 5 DNA sequences and primary hepatocellular carcinoma associated with chronic hepatitis B virus infection in a patient.

In a case of epidermodysplasia verruciformis with impaired cell-mediated immunity and multiple skin cancers human papillomavirus type 5 (HPV5) DNA sequences were demonstrated in a cutaneous squamous cell carcinoma. HPV5 and HPV8 were detected in the benign disseminated skin lesions together with three newly characterized HPVs: HPV17, HPV19 and HPV24. A chronic infection with hepatitis B virus resulting in macronodular cirrhosis associated with a primary hepatocellular carcinoma was also acquired by this patient. This case provides an example of the circumstantial evidence which suggests that certain types of HPV are potentially oncogenic and stresses the importance of immune surveillance in the protection against virus-associated tumors.

Adult↗

Diagnostic significance of nailfold capillary patterns in patients with Raynaud's phenomenon. An analysis of patterns discriminating patients with and without connective tissue disease.

Nailfold capillary patterns were systematically evaluated in 51 controls and 107 patients with Raynaud's phenomenon (RP) by 2 observers. Fifty patients had primary RP, 18 RP with minor signs of connective tissue disease, and 39 secondary RP (scleroderma, CREST syndrome or mixed connective tissue disease [MCTD]). Nailfolds of all 10 fingers were photographed and blindly evaluated. Qualitative and quantitative scoring of patterns was reproducible. The 4th finger showed the fewest nonevaluable photomicrographs and best distinguished primary from secondary RP. Capillary morphology in primary RP did not differ from controls. A decrease in capillary loops best distinguished primary from secondary RP. Addition of the scores for bushy patterns, extravasates, or giant loops led to better discrimination. No item allowed distinction between different connective tissue diseases. The number of enlarged loops was inversely related to the total number of capillary loops (r = 0.55; p less than 0.01).

Adult↗

HLA-B8/DR3 phenotype and the primary immune response.

Increased frequency of HLA-B8/DR3 has been reported in many organ-specific and systemic autoimmune diseases. Immune responsiveness in 11 normal subjects with and 22 without the B8/DR3 phenotype was studied. The IgA class immune response after immunization with the primary test immunogen alpha-Helix pomatia hemocyanin (HPH) was increased in B8/DR3-positive subjects compared to the non-B8/DR3 group. Also, IgG class antibody levels tended to be higher in the former group. The in vitro lymphocyte proliferative response to optimal concentrations of HPH did not differ between the groups nor did the response to allogeneic cells. Lymphocyte proliferation on stimulation with pokeweed mitogen and suboptimal concentration of phytohemagglutinin was increased in B8/DR3 individuals. It is concluded that the phenotype B8/DR3 is associated with a high humoral immune response.

Adult↗

The primary immune response in bronchial asthma. I. A kinetic study of Helix pomatia hemocyanin-specific IgE, IgG, IgA, and IgM antibody responses in patients with asthma and in matched controls.

Eleven asthmatic patients with allergy and 10 age- and sex-matched controls were immunized subcutaneously with 1 mg of the primary test immunogen Helix pomatia hemocyanin (HPH). The HPH-specific IgE, IgG, IgA, and IgM antibody response was measured by ELISA. After immunization, not only the IgE but also the IgG antibody response of the patients exceeded that of the controls (p less than 0.01). IgA antibody response also tended to be higher in the asthmatic group (NS). Except for an earlier rise after immunization in the asthmatic group (p less than 0.05), IgM peak responses did not differ significantly between the two groups. There was a high correlation (r = 0.9) between the magnitude of the IgE and the IgG antibody responses. IgM antibody response did not correlate with the response in any of the other antibody classes measured. The total serum immunoglobulin concentration was determined before immunization. Only the IgE level was significantly higher in the asthmatic group (p less than 0.01). No correlation was found between serum immunoglobulin concentrations and the magnitude of the HPH-specific antibody response in the same class. We conclude that the increased humoral responsiveness of asthmatic patients with allergy is not restricted to the IgE class nor to a limited number of commonly encountered antigens (allergens).

Adult↗

Decreased nailfold capillary density in Raynaud's phenomenon: a reflection of immunologically mediated local and systemic vascular disease?

Nailfold capillary patterns were studied in 107 patients with Raynaud's phenomenon (RP), including patients wih (n = 39) and without (n = 68) connective tissue disease (CTD). Capillary density was decreased in patients with sclerodactyly, digital ulcers, tuft resorption, and telangiectasia, compared with patients without these symptoms. In addition, an inverse relationship was found between the severity of RP at first presentation (as graded by photoelectric plethysmography during cooling) and the capillary density in patients with CTD (r = -0.45; p less than 0.05). In the total group of patients nailfold capillary density was inversely related to organ system involvement (r = -0.52; p less than 0.01). Decreased nailfold capillary density was observed, in particular, in patients with oesophageal hypomotility and in patients with chest x-rays compatible with interstitial fibrosis. As to factors supposedly involved in the pathogenesis of vascular changes in CTD, the presence of autoantibodies, increased levels of circulating immune complexes, and increased levels of acute phase reactants were all associated with a decreased number of nailfold capillaries. We conclude that loss of nailfold capillaries as observed by microscopy is a reflection of local and systemic vascular disease.

Adult↗

Scl-86, a marker antigen for diffuse scleroderma.

More than 300 sera from patients with a connective tissue disease were analyzed with the immunoblotting technique. The presence of autoantibodies against an 86,000-mol wt marker antigen for diffuse scleroderma (Scl-86) was found in 14 out of 33 patients with scleroderma. The presence of anti-Scl-86 antibodies seemed to correlate with the diagnosis of diffuse scleroderma since they were found in 13 out of 22 diffuse scleroderma patients and in only one out of 11 patients with limited scleroderma. All scleroderma sera (33 patients' sera and 13 reference sera) were also tested for the presence of anti-Scl-70 antibodies. It was found that all anti-Scl-70 positive sera (n = 25) contained anti-Scl-86 antibody as well, suggesting a relationship between these two antigens. However, the Scl-86 antigen was shown to be an extremely insoluble nonchromosomal protein, resistant to boiling in sodium dodecyl sulfate. This contrasts with the Scl-70 antigen, which has been described as a thermolabile, soluble antigen present in the chromatin fraction. Together, our results are consistent with the idea that Scl-70 is a degradation product of Scl-86. The Scl-86 antigen is present in freshly prepared rabbit thymus, spleen, and liver nuclei as well as in nuclei from various cultured cell lines, but is not detectable in extractable nuclear antigen from rabbit thymus. In a limited retrospective study, the anti-Scl-86 antibodies were found in two sera from patients with Raynaud's phenomenon before the development of diffuse scleroderma. Therefore, it is possible that screening of patients' serum for this antibody might predict the development of diffuse scleroderma.

Animals↗

Quantitation of antibodies to nucleoribonucleoprotein by ELISA: relation between antibody levels and disease activity in patients with connective tissue disease.

We describe a solid-phase enzyme-linked immunosorbent assay (ELISA) for quantitation of antibodies to nucleoribonucleoprotein (nRNP/Sm). nRNP/Sm was purified from rabbit thymus acetone powder by immunoaffinity chromatography and characterized by counterimmunoelectrophoresis (CIE) and immunoblotting using sera with well-known specificities. The purified antigen was used in ELISA. Positive results in ELISA were obtained only in sera with anti-nRNP or anti-Sm specificity as determined in CIE. Levels of anti-nRNP/Sm as quantitated by ELISA were higher in the sera of patients with active connective tissue disease (n = 7) than in those with inactive disease (n = 6) (P less than 0.01). Differences in anti-nRNP/Sm levels were also found between patients with mildly active disease (n = 19) and those with active disease (P less than 0.01). Fluctuations of anti-nRNP/Sm levels related to disease activity were seen in longitudinal observation. Although anti-nRNP/Sm levels as quantitated by ELISA correlated with titres of antinuclear antibodies as determined by immunofluorescence (r = 0.46, P less than 0.05), quantitation of anti-nRNP/Sm by ELISA is superior since the assay is antigen-specific and its quantitation independent of titration-related inaccuracies.

Adult↗