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Biomedical subjects

J Pinkhas

Publications and source records attributed to J Pinkhas.

At least 55 records · Page 3Linked to original sources

Evaluation of disease activity in rheumatic patients by leucocyte adhesiveness/aggregation.

Previous work has shown that leucocyte adhesiveness/aggregation (LAA), as measured by the leukergy test, correlates well with disease severity in rheumatic patients. As LAA is probably a manifestation of the acute phase reaction various components of the acute phase reaction were measured in order to identify the best marker of disease activity. In addition to LAA, the following variables were measured in 79 patients with various rheumatic diseases and in 10 controls: white blood cell and platelet counts, erythrocyte sedimentation rate, haptoglobin, fibrinogen, C reactive protein, albumin, globulin, caeruloplasmin, alpha 1, alpha 2, beta, and gamma globulin, and haemoglobin concentrations. Patients were graded according to the state of their disease as mild, moderate, or severe. The extent of leucocyte adhesiveness/aggregation in peripheral blood proved to be the best laboratory variable for the grading of disease activity. Correct grading was obtained in 63% of the patients by means of the LAA, compared with 48% with C reactive protein, 41% with caeruloplasmin, 40% with haptoglobin, and 32% with haemoglobin. It is suggested that LAA of the peripheral blood during inflammation may be used as a reliable marker of disease severity.

Adolescent↗

Theophylline prolongs survival and decreases renal damage in female NZB/W F-1 mice.

Theophylline (Th) augments suppressor T cell activity (STCA). We attempted to test this immunoregulatory effect of TH on survival, renal disease and several immunologic parameters in NZB/W F-1 female mice. The median survival was 274 +/- 50 days for the mice receiving Th and 235 +/- 39 days for the controls (p less than 0.01). Assessment of the extent of renal damage by light microscopy revealed activity scores of 1.86 +/- 2 and 4.71 +/- 2.7 for the Th and control groups, respectively (p less than 0.001). T cell activity of NZB/W F-1 lymphocytes was assessed by the local xenogeneic GVH reaction. The mean GVH reaction volume of the Th group was significantly lower (9.3 +/- 8.8 mm3) as compared to controls (31 +/- 9 mm3) (p less than 0.001). The proportion of Lyt-1 versus Lyt-2 spleen lymphocytes did not change significantly. It is concluded that Th prolongs survival and decreases the extent of renal damage in female NZB/W F-1 mice.

Animals↗

HLA antigens in patients with Heberden's nodes.

Tissue typing was performed on a group of 51 patients with Heberden's nodes (HN) (45 Ashkenazic and 6 non-Ashkenazic Jews). The frequency of HLA-DR2 was higher (P = 0.03) in the Ashkenazic patients than in the Ashkenazic controls. However, the association was not significant after correction for the number of tested alleles at that locus. In the second part of the study, HLA typing was performed on subjects from a family with multiple HN occurrences. Of the 13 family members typed, 9 had HN: 6 of these had the haplotype A2, Bw35, DR2. We conclude that the development of HN may be influenced by genetic factors. Our results may suggest an association between HN and HLA-DR2 in Ashkenazic Jews.

Female↗

Synergism between zymosan-activated serum and heparin in the induction of polymorphonuclear leukocyte aggregation.

During the course of extracorporeal circulation, leukocyte aggregation is known to occur in some patients. This is attributed to complement activation and release of the chemotactic factor C5a. We investigated the effect of heparin on in vitro complement induced aggregation of polymorphonuclear leukocytes (PMNAGG), since most patients undergo heparinization during the extracorporeal circulation. Our results indicate that sub-aggregating concentrations of zymosan-activated serum (ZAS) enhance heparin-induced PMNAGG and that sub-aggregating amounts of heparin increase the aggregation induced by ZAS. Heat inactivation of the serum prior to zymosan activation abrogated the aggregating activity of the ZAS. Furthermore, the combined ZAS and heparin-induced PMNAGG was partially inhibited by specific antibodies to C5a but not to C3a. Therefore, we suggest that heparin and C5a may have a synergistic effect on the aggregation of polymorphonuclear leukocytes. These data might be relevant to situations in which patients are subjected to extracorporeal circulation.

Cell Aggregation↗

Possible role of fibrinogen in the aggregation of white blood cells.

In order to verify whether leukocyte aggregation correlated with aggregation of other cellular elements during inflammation, we examined the state of leukocyte adhesiveness/aggregation (LAA) in the peripheral blood and red cell aggregation. Correlation was found to be significant as was the correlation between LAA and fibrinogen, and with the fibrin/fibrinogen degradation products concentration during various inflammatory states. In vitro leukocyte aggregation was decreased when the cells were suspended in autologous heat defibrinogenated plasma as compared to cells suspended in autologous native plasma. Heat aggregated fibrinogen but not native fibrinogen caused leukocyte aggregation in vitro. Finally, Arvin defibrinogenation in rabbits reduced the state of LAA in endotoxinemic rabbits. Integrating all this information, we assume that fibrinogen participates not only in the aggregation phenomena of red cells and platelets, but also in those of leukocytes.

Animals↗

Human monoclonal antibodies derived from lymph nodes of a patient with breast carcinoma react with MuMTV polypeptides.

Nine human hybridoma cell lines were established from a fusion of axillary lymph node lymphocytes of a patient with breast ductal carcinoma with a human lymphoblastoid cell line. The human hybridoma nature of the fusion products was confirmed by chromosomal analysis and HLA typing. The hybridomas are stable over a year of growth, and can be frozen, thawed and regrown. The carcinoma cells of the patient harbor mouse mammary tumor virus (MuMTV) cross-reacting antigens. The patient's serum and the purified monoclonal antibodies reacted with MuMTV polypeptides. Radioimmunoprecipitation studies using labeled MuMTV confirmed the binding of the patient's serum to the viral proteins. None of the control immunoglobulins reacted with the virus. No binding of the hybridoma immunoglobulins was observed with two other retroviruses (avian myeloblastosis virus and simian sarcoma virus). The ligand binding characteristics of the monoclonal antibodies suggest binding to epitopes on the various structural virus polypeptides. These monoclonal antibodies may serve as a probe to analyze the MuMTV-human breast carcinoma relationship.

Adult↗

A common anti-DNA idiotype in sera of patients with active pulmonary tuberculosis.

The sera of 57 patients with active, untreated pulmonary tuberculosis were examined for the presence of a common anti-DNA idiotype, 16/6. Thirty-four of the 57 sera (60%) had an increased level of the idiotype, as measured by enzyme-linked immunosorbent assay using a specific rabbit anti-16/6 serum. Of 28 matched control sera, only 1 (4%) was found to be positive for the idiotype. The sera of patients with tuberculosis also showed increased activity against a variety of antigens with which lupus autoantibodies are known to crossreact (e.g., single-stranded DNA, double-stranded DNA, polynucleotides, and cardiolipin). A correlation was observed between serum IgG and IgM levels and the 16/6 idiotype levels.

Adult↗

Juxta-articular adiposis dolorosa associated with rheumatoid arthritis. Report of 2 cases with good response to local corticosteroid injection.

Juxta-articular adiposis dolorosa, i.e., painful fatty deposits around the joint may occur in postmenopausal obese women. The association of the syndrome with osteoarthritis has been described. The present report describes 2 women suffering from rheumatoid arthritis with painful fatty deposits around the knees. Both responded to local injection of corticosteroid. The possible pathogenesis of the source of pain is discussed.

Adiposis Dolorosa↗

Aggregation of white cells and C-reactive protein: relation between these two indices in acute phase reaction.

The association between aggregates of leucocytes in blood drawn from patients with various inflammatory conditions and the serum concentration of C-reactive protein (CRP) was examined: serum concentration of CRP might contribute to the development of cellular aggregations. A total of 213 patients with various inflammatory or necrotic conditions were examined (including 31 women with normal pregnancy and 59 controls). A significant correlation between the degree of leucocyte aggregation and CRP concentration was noted in patients with bacterial infections and in a group of patients with various inflammatory conditions. In contrast, there was no correlation between the extent of leucocyte aggregation and CRP concentrations in patients with viral infections, malignancies, or pregnancy. The presence or absence of aggregated leucocytes can help in differentiating between the respective bacterial or viral infections. The serum concentrations of CRP were increased in both types of infection, although when a quantitative CRP assay was used, considerably higher concentrations were detected in bacterial diseases.

Acute-Phase Reaction↗

Transcutaneous electrical nerve stimulation in experimental acute arthritis.

Transcutaneous electrical nerve stimulation (TENS) is applied for the relief of various types of pain, including rheumatoid arthritis and osteoarthritis. This study evaluated the influence of TENS on intraarticular (IA) temperature and pressure and synovial tissue of inflamed rabbit joints. Four hours after induction of acute bilateral hind joint arthritis by single intraarticular injection of urate crystals, the knees of 14 anesthetized rabbits were fixed at 90 degrees between femur and tibia. TENS was supplied from an electrical stimulator to the left knee joint while the other joint was unstimulated as a control. A microprobe needle for temperature measurement was inserted into the knee joint. Intraarticular pressure was recorded by polygraph connected to an IA needle. Readings were carried out at 10-min intervals three times before and four times after 5 min of TENS. A significant increase in IA temperature from mean 36.2C to 36.6C and significant reduction of IA pressure (mean decrease of 0.8 mmHg, from 2.5 mmHg to 1.7 mmHg) were found in the stimulated joints, which also showed a reduction of synovial fluid volume and total leukocyte count in comparison to the controls. While the nonstimulated synovial membrane showed massive leukocytic infiltration with neutrophilic exudate and fibrin clot in the intraarticular cavity, the stimulated synovial membrane demonstrated moderate homogeneous leukocytic infiltration through all layers, with absence of inflammatory exudate in the intraarticular cavity. These results suggested that the analgesic effect of TENS on arthritis may be partially attributed to decrease in IA synovial fluid pressure, volume, and leukocyte count. Therefore, TENS may be useful for reducing pain from inflammatory arthritis.

Animals↗

Transcutaneous electrical stimulation of the normal rabbit joint.

To determine the effect of transcutaneous electrical stimulation on the rabbit joint, we studied skin and intraarticular temperatures and pressure both before and following the stimulation in nine rabbits. An elevation in skin temperature by a mean of 0.6 degrees C (p less than 0.05) and increase in intraarticular temperature by a mean of 0.8 degrees C (p less than 0.01) was noted following the electrical stimulation. Intraarticular pressure in the stimulated joints has only a trend to increase, but not significantly. In four other rabbits, synovial tissue of the stimulated joint showed blood vessels congestion and interstitial edema. These results suggest that the analgetic effect produced by electrical stimulation on joints may partially involve intraarticular temperature and pressure alterations.

Animals↗

Idiopathic deep vein thrombosis in an apparently healthy patient as a premonitory sign of occult cancer.

An association between migratory venous thrombosis or acute pulmonary embolism and occult cancer has been previously suggested. The relationship between the commoner deep venous thrombosis (DVT) in an otherwise healthy individual and occult cancer is not known. The incidence of cancer in 35 otherwise healthy patients with idiopathic DVT (group A) was compared to 48 patients with DVT due to a known etiology, excluding cancer (group B). In 12 patients of group A (34%), a diagnosis of cancer was established 4-68 months after the DVT episode, compared to 2 patients of group B (4%) (P = 0.001). The origin of the earliest discovered cancer (up to 8 months) was the reproductive organs (ovary, endometrium, prostate, breast), while the later discovered malignancies were of colon, pancreas, lung and a lymphoma. At the initial idiopathic DVT episode, patients found subsequently to have cancer, were older than the control group (P less than 0.01), had hemoglobin concentration lower than 12.4 g/dl (P less than 0.02), and had eosinophil counts higher than 3% (P less than 0.01). A score devised from these parameters could identify 83% of the patients with cancer and 91% of those without malignancy (P = 0.00003). These findings indicate that there is a correlation between idiopathic DVT and occult cancer and that the majority of the patients at risk may probably be identified early by the score devised.

Age Factors↗

Leukocytosis in non hematological malignancies--a possible tumor-associated marker.

Leukocytosis (WBC counts 10,000/mm3) was detected in 77 out of 252 patients (30%) with ten different types of nonhematological malignancy (NHM) at the time of diagnosis. A full search including serological and bacteriological screening was performed to exclude other possible causes of leukocytosis. Among the different tumors, carcinomas of the lung and colorectum were the most prevalently associated with leukocytosis. Absolute monocytosis was found in 25% of the patients and absolute eosinophilia in only 4.8%. The leukocytosis was attributed mainly to an increase in the mature polymorphonuclears, suggesting a release mechanism of WBC from storage pools by factors secreted or induced by the tumor. Neither the age nor the sex of the patients affected the incidence or magnitude of leukocytosis. However, the presence of metastases was associated with a significantly higher incidence of leukocytosis (p less than 0.05). The associated leukocytosis may be regarded as a poor prognostic sign, and was associated with a significantly (p less than 0.007) shorter survival time. In contrast, absolute lymphocytosis may have a positive effect on the survival time (p = 0.01). Tumor-associated leukocytosis may be an additional tumor-associated marker, of value in assessing and monitoring patients with NHMs.

Female↗