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A study was undertaken to isolate pure human antisperm antibodies from the sera of infertile couples. One hundred infertile couples attending the Infertility and IVF Unit (Beilinson Medical Center) because of unexplained infertility were tested (both partners) for antisperm antibodies. Sixty-eight experiments were performed with positive sera containing antisperm antibodies and normal donor sperm. These experiments were followed by experiments in order to elute pure human antisperm antibodies from the sperm surface. Three experiments were performed with human sperm which were found to be coated by antisperm antibodies, in order to directly elute these antibodies from the sperm surface. In all experiments we eluted antisperm antibodies of the IgG and IgA isotypes from the sperm surface. These antibodies were demonstrated in the eluate, in each case by either the indirect immunobead test, the radial immune diffusion assay, or the electrophoresis method. Control experiments were performed as follows: (i) normal donor sperm incubated with normal serum; (ii) normal donor sperm without serum incubation; (iii) normal donor lymphocytes incubated with serum containing antisperm antibodies; (iv) normal donor lymphocytes without serum incubation. No antisperm antibodies were obtained in any of these control experiments. Absorption and elution experiments can be used for the isolation of pure human antisperm antibodies, which may then be used for the production of anti-idiotypic antibodies to antisperm antibodies. The anti-idiotypic antibodies could be further utilized as antigen substitutes for the production of a contraceptive vaccine and/or for application in the treatment of spontaneous abortion and infertility.

We present the case of a patient whose semen contained 30% of sperm with double heads and double tails at various stages of attachment due to abnormal meiosis. The genital system, sperm density, endocrinological profile and karyotype were normal. It is postulated that abundance of the above-noted type of sperm pathology in the human semen might not necessarily be associated with oligozoospermia or fertility impairment.

Lymphocytes were obtained from a lymph node biopsy from a patient with chronic lymphocytic leukemia in whom B and T lymphocytes were present in equal percentages in the peripheral blood. The lymphocytes were examined for rosette formation with mouse and sheep erythrocytes in order to determine whether the leukemic process was of the B or T cell type.

Human T lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 infection in patients with B cell-type chronic lymphocytic leukemia (B-CLL) is rare and has been reported only in areas in which HTLV-1 is endemic. In the present study, we detected HTLV-1 proviral DNA by polymerase chain reaction, using tax primers, in peripheral blood lymphocytes from a B-CLL patient, an immigrant to Israel, where HTLV-1 infection is not endemic. F344 rats injected intravenously with peripheral blood lymphocytes obtained from the patient developed HTLV-1 antibodies. Titers of antibody to HTLV-1 in the rat blood were 1:512 by particle agglutination; enzyme-linked immunosorbent assay and Western blotting were also positive. No antibody against HTLV-1 was demonstrated in the animal model after inoculation of either purified B lymphocytes from the B-CLL patient or peripheral blood mononuclear cells from healthy donors. This is one of the few studies showing the presence of HTLV-1 provirus in T lymphocytes of a B-CLL patient who had multiple infections, and died of salmonella sepsis, and the first report of HTLV-1 antibody induction in an animal model by inoculation of lymphocytes obtained from an HTLV-1-infected B-CLL patient.

The aetiology of mycosis fungoides (MF) and Sezary syndrome (SS) is unknown. A pathogenic role for the human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. We used an animal model to test the possibility that peripheral blood mononuclear cells (PBMC) obtained from MF patients harbour the HTLV-1 virus which may be infective. The polymerase chain reaction (PCR) was used to detect HTLV-1 proviral DNA sequences in PBMC of 27 MF patients and one SS patient of non-Iranian origin. Positive results were found in six of the patients. Twelve of the 28 patients tested by Western blot showed HTLV-1 antibodies. Twenty-eight immunosuppressed inbred Fisher F344 rats were inoculated intravenously with cultures of PBMC obtained from the 28 patients. Eight of these 28 rats showed antibodies to HTLV-1 while the proviral genome was demonstrated in the blood of only two of the rats. PBMC from two MF patients, in spite of showing negative results for the proviral genome by PCR, still induced HTLV-1 antibody formation in the F344 rat model. None of 10 control rats inoculated with normal donor PBMC showed antibodies to HTLV-1, nor the proviral genome. The present study suggests that HTLV-1 plays a cofactor role in MF/SS patients.

The immunological dysfunction observed in B-chronic lymphocytic leukaemia (B-CLL) is often related to T-lymphocyte incompetence. The local xenogeneic graft-vs.-host reaction (XGVHR), an assay to evaluate T-lymphocyte function, was performed in 112 untreated B-CLL patients. The XGVHR results significantly correlated with clinical parameters: 37.1% of the patients in the stable phase (Rai stage 0-1-2) and only 13.3% of the patients in the progressive phase (Rai stage 3-4) had positive XGVHR results. Patients with negative results had a higher number and percentage of lymphocytes (25,247 vs. 17,071/microliter and 75.9% vs. 65.6%, respectively), much lower T/B lymphocyte ratio (0.37 vs. 0.93), higher WBC count (30,977 vs. 23,458/microliter), lower platelet count (158,068 vs. 181,684/microliter) and lower levels of IgA and IgM (115.6 vs. 200.5 mg/dl and 80.4 vs. 124.3 mg/dl, respectively) compared to those with positive results. Among those with negative XGVHR results, a higher mortality rate was found in those who had infections compared with those who did not (73.7% vs. 9.1%). In conclusion, the XGVHR assay significantly correlates with important characteristics of B-CLL and may be useful in the clinical evaluation of B-CLL patients.

We tested the possibility that lymphocytes and serum obtained directly from a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) induce infection in rats. Inbred Fischer F344 immunosuppressed rats were inoculated intravenously with 10x10(6) peripheral blood mononuclear cells (PBMC; 3 rats) and serum (3 rats) obtained from a HAM/TSP patient, who was seropositive and polymerase chain reaction (PCR)-positive for the HTLV-I proviral genome. Antibodies to HTLV-I appeared in the rat sera 2 months later; rat peripheral blood lymphocytes, spleen, salivary gland, and spinal cord were found to contain the proviral genome. Control rats inoculated with normal donor PBMC and serum tested negative for the HTLV-I antibodies and for the HTLV-I proviral genome by PCR. The positive control F344 rats inoculated with 5x10(6) cells of a SLB-1 HTLV-I cell line were found to be infected after 2 months. This study demonstrates for the first time that HTLV-I can be transmitted not only by human cellular components but also by human cell-free sera in a rat model.

A high prevalence of human T-lymphotropic virus type I (HTLV-I) infection among Israeli Jews was previously reported. In the present study, screening for HTLV-I of Israeli Jews was expanded to 10 ethnic groups. HTLV-I antibodies were tested by the particle agglutination assay, ELISA, and by Western blot as a confirmatory method. The HTLV-I proviral genome was tested by nested PCR with tax primers (SK43/SK44 and Tr101/Tr102). The PCR tests were carried out in all seropositive subjects and the seronegative family members of the seropositives subjects in the Iranian population. Sixty-eight of the 1,679 subjects (4.1%) were found to be seropositive. The Jews originating from Mashhad had the highest infection rate of 60/306 (20%). Of the 479 Iranian non-Mashhadi Jews, 6 (1.3%) were seropositive. Of the 894 non-Iranian Israelis, only 2 (0.2%) were seropositive. HTLV-I proviral DNA was found in the peripheral blood lymphocytes of 66 out of 68 seropositive subjects and 6 out of 75 seronegative subjects. Sixty out of 123 (49%) Mashhadi Jews and 8 out of 14 (57%) non-Mashhadi Iranian Jews were PCR-positive. Three out of three seropositive non-Iranian Israelis were PCR positive. One non-Iranian Israeli (who originated from Ukraine) without family connections to the Iranian Jews was also PCR-positive. One hundred eighteen saliva samples (84 from subjects of Mashhadi origin, 31 from Iranian origin, and 4 of other origins) were also screened. Antibodies for HTLV-I were found in 23 out of 46 saliva samples from the individuals with particle agglutination (PA) and/or PCR-positive findings in blood. Twenty out of 23 PA-positive saliva samples also contained the proviral DNA. It is concluded that HTLV-I infection in Israel is mainly limited to Jews originating from Iran (most of them from Mashhad) and their family members.

High prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection and disease has been identified among Iranian-born Mashhadi Jews, an ethnically segregated, highly inbred population. To determine the origin and genetic diversity of HTLV-I in this group, 1,039 bp spanning selected regions of the HTLV-I gag, pol, env and pX genes were enzymatically amplified and sequenced directly from DNA of five Mashhadi Jews (three with spastic myelopathy and two asymptomatic carriers). Alignment and comparison of these sequences with cosmopolitan and Australo-Melanesian topotypes of HTLV-I indicated that the HTLV-I strains from Mashhadi Jews, which were > or = 99.9% identical among themselves, exhibited considerable sequence similarity (> or = 99%) to HTLV-I strains from southern India, suggesting a common source of infection. Phylogenetic analysis, using the maximum parsimony method, was consistent with a single-source introduction of HTLV-I into the Mashhadi Jewish community.

T-lymphocyte levels may adversely affect the clinical course and outcome of patients with acute myocardial infarction (AMI). To characterize the T-lymphocyte profile during AMI and to explore whether these cells play a detrimental role in the extent of myocardial insult, levels of T-lymphocyte subpopulations, free soluble interleukin-2 receptor (sIL-2R), and interleukin-1 beta (IL-1 beta), were measured during the first week of AMI. Results were correlated with left ventricular ejection fraction (LVEF), age, sex, survival rate, thrombolytic therapy, and the occurrence of reinfarction. Thirty-nine patients, 20 men and 19 women aged 30 to 80 years, with first AMI were included. Patients were divided into two groups. Group A (13 patients) experienced reinfarction; group B (26 patients) did not. T-helper and-suppressor cells were measured by the indirect immunofluorescence method and sIL-2R and IL-1 serum levels by enzyme-linked immunosorbent assay (ELISA) methods on days 1, 4, and 7 after AMI. A low count of T-helper cells (CD4) was found on the first day after AMI in both AMI groups; however, the count returned to normal in group B but not in group A. A significant correlation (r = 0.63) was found between T-helper cell count on day 4 of AMI and LVEF assessed by radionuclide ventriculography, and between the CD4/CD8 ratio on day 1 and the creatine phosphokinase level (r = -0.6950). High sIL-2R levels were found in groups A and B of the AMI patients as compared with the control group (p < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Exogenous interleukin-1 (IL-1) has been shown to confer radioprotection to normal tissues. However, there is little information on the effects of radiotherapy on endogenous cytokine production. The purpose of this study was to examine the influence of breast radiotherapy on plasma IL-1 levels and lymphocyte subpopulations in patients with early-stage breast cancer. IL-1 and lymphocyte subsets were determined in 13 patients before and after radiation therapy utilizing specific immunologic assays. Local radiation to the breast caused significant reduction in plasma IL-1 levels (mean 269 ± 177 vs. 3 ± 50 pg/ml, P < 0.01). This was accompanied by a marked decrease in the lymphocyte counts of all patients (1850 ± 560 vs. 1013 ± 344, P < 0.05). Local radiotherapy can have a significant effect on systemic cytokine levels that may potentially impact on the radiation response of normal tissues and tumors. To our knowledge this is the first report of the effect of local radiotherapy on plasma levels of IL-1. It is hoped that this may provide further insights into the biological responses to radiation and their impact on clinical outcome. © 1995 Wiley-Liss, Inc.

Total peripheral T lymphocytes, OKT4 helper/inducer cells and OKT8 suppressor/cytotoxic cells, as well as T lymphocyte function determined by the local xenogeneic graft-versus-host reaction (GVHR), were investigated in 14 psoriatic patients prior to institution of treatment with etretinate, during the course of treatment and 6 months after its initiation. After approximately 2 months of treatment, there was a significant increase in the number of E-rosette-forming lymphocytes and OKT4 subpopulations with a return to normal levels after 6 months of treatment. The GVHR was positive in only 5/11 patients prior to therapy but in 9/11 patients after 2 and 6 months. Our results indicate that etretinate has a stimulatory effect on T lymphocytes and their subset counts.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma of unknown aetiology. A pathogenic role of human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. To determine whether MF is linked to HTLV-1.Blood samples were collected from 60 patients, 15 family relatives of patients with MF (MFRs), 20 healthy controls and 10 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The presence of HTLV-1 antibodies in serum was tested by the Western blot rp21e-enhanced test. DNA was extracted from the blood with the Qiagen blood kit. We used 500 ng of DNA either in conventional HTLV-1-specific polymerase chain reaction (PCR) or in real-time PCR using primers sk43 and sk44 together with a tax-specific fluorescent probe.In Western blot, antibodies against three to four HTLV-1 antigens were detected in 52% of patients with MF. All of the patients with HAM/TSP were positive, while only 7% of the MFRs and none of the 20 healthy controls reacted with HTLV-1 antigens in Western blot. One of 60 patients with MF and one of 15 MFRs were positive in HTLV-1 PCR. These two PCR-positive samples which were quantified in real-time PCR showed that fewer than five in 10(6) cells were HTLV-1 infected. We succeeded in amplifying and sequencing the 5' end of the provirus from the blood of the PCR-positive MFR by seminested PCR. A positive result was also obtained in this test. Phylogenetic tree analyses revealed a high homology of this sequence with other HTLV-1 sequences from the Middle East. The above PCR-positive MFR was the brother of a PCR-negative patient with MF.These findings demonstrate that HTLV-1 is probably not the aetiological agent of MF. However, it may play a role in immunosuppression and in the spreading of the disease.

1,25-Dihydroxycholescalciferol [1,25(OH) 2 D], besides its role in calcium and phosphorus homeostasis, is also an important immunoregulatory molecule. Plasma levels of this hormone may be normal or elevated in patients with primary hyperparathyroidism. 1,25(OH) 2 D has been reported to inhibit production of the cytokines interleukin-2 (IL-2) and IL-6. In the present study, we examined the effect of parathyoid adenoma excision on serum IL-2 receptor (IL-2R) levels and the release and production of IL-2R and IL-6 by perpheral blood lymphocytes (each measurement was perofmred twice). Ten patients (5 females and 5 males aged 45 to 78 years) with primary hyperparathyroidism were enrolled in the study. The diagnosis of primary hyperparathyroidism was based on the presence of asymptomatic hypercalcemia, hypophosphatemia, and elevated serum intact PTH levels. Three weeks after removal of the parathyroid adenoma, there was a significant increase in the serum level of IL-2R, as well as the PHA-stimulated peripheral blood lymphocyte production of IL-6 and release of IL-2R. The results indicate that the removal of a parathyroid adenoma in patients with primary hyperparathyroidism causes a significant increase in IL-2R and IL-6 levels. The mechanism by which hyperparathyroidism may affect these cytokines and how they seem related to the levels of vitamin D is discussed.

Reports from Jamaica have indicated that some patients with infective dermatitis or atopic dermatitis (AD) are seropositive for antibodies to human T-lymphotropic virus type 1 (HTLV-1). We describe a 32-year-old Israeli woman with long-term AD and paresthesia in the distal parts of the extremities. Neurological examination revealed a positive Babinski’s sign. HLA typing demonstrated that this patient has the common HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis haplotype for DRB1* DQB1*. The presence of HTLV-1 was demonstrated with polymerase chain reaction; HTLV-1-antibodies were detected by the Western blot method and by inoculation of the patient’s peripheral blood mononuclear cells into F344 rats. This study confirms the presence of HTLV-1 antibodies and proviral genome in a patient with AD which later evolved into HAM/TSP. We cannot yet conclude whether these two diseases are associated or coincidental disorders.

The aetiology of mycosis fungoides (MF) and Sézary syndrome (SS) is unknown. A pathogenic role for the human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. We used an animal model to test the possibility that peripheral blood mononuclear cells (PBMC) obtained from MF patients harbour the HTLV-1 virus which may be infective. The polymerase chain reaction (PCR) was used to detect HTLV-1 proviral DNA sequences in PBMC of 27 MF patients and one SS patient of non-Iranian origin. Positive results were found in six of the patients. Twelve of the 28 patients tested by Western blot showed HTLV-1 antibodies. Twenty-eight immunosuppressed inbred Fisher F344 rats were inoculated intravenously with cultures of PBMC obtained from the 28 patients. Eight of these 28 rats showed antibodies to HTLV-1 while the proviral genome was demonstrated in the blood of only two of the rats. PBMC from two MF patients, in spite of showing negative results for the proviral genome by PCR, still induced HTLV-1 antibody formation in the F344 rat model. None of 10 control rats inoculated with normal donor PBMC showed antibodies to HTLV-1, nor the proviral genome. The present study suggests that HTLV-1 plays a cofactor role in MF/SS patients.

A high prevalence of human T-lymphotropic virus type I (HTLV-I) infection among Israeli Jews was previously reported. In the present study, screening for HTLV-I of Israeli Jews was expanded to 10 ethnic groups. HTLV-I antibodies were tested by the particle agglutination assay, ELISA, and by Western blot as a confirmatory method. The HTLV-I proviral genome was tested by nested PCR with tax primers (SK43/SK44 and Tr101/Tr102). The PCR tests were carried out in all seropositive subjects and the seronegative family members of the seropositives subjects in the Iranian population. Sixty-eight of the 1,679 subjects (4.1%) were found to be seropositive. The Jews originating from Mashhad had the highest infection rate of 60/306 (20%). Of the 479 Iranian non-Mashhadi Jews, 6 (1.3%) were seropositive. Of the 894 non-Iranian Israelis, only 2 (0.2%) were seropositive. HTLV-I proviral DNA was found in the peripheral blood lymphocytes of 66 out of 68 seropositive subjects and 6 out of 75 seronegative subjects. Sixty out of 123 (49%) Mashhadi Jews and 8 out of 14 (57%) non-Mashhadi Iranian Jews were PCR-positive. Three out of three seropositive non-Iranian Israelis were PCR positive. One non-Iranian Israeli (who originated from Ukraine) without family connections to the Iranian Jews was also PCR-positive. One hundred eighteen saliva samples (84 from subjects of Mashhadi origin, 31 from Iranian origin, and 4 of other origins) were also screened. Antibodies for HTLV-I were found in 23 out of 46 saliva samples from the individuals with particle agglutination (PA) and/or PCR-positive findings in blood. Twenty out of 23 PA-positive saliva samples also contained the proviral DNA. It is concluded that HTLV-I infection in Israel is mainly limited to Jews originating from Iran (most of them from Mashhad) and their family members.

Using in situ hybridization, the presence of T-cell lymphotrophic virus type I (HTLV-I) was shown in blood lymphocytes of one tropical spastic paraparesis (TSP/HAM) patient and in two asymptomatic carriers. HTLV-I was also detected in epithelial cells derived from mouthwash of the TSP/HAM patient. Mouthwash of one of the carriers showed an infected lymphocyte while mouthwash of the other carrier was negative. The infected epithelial cells stained both in the nucleus and in the cytoplasm, which indicated the presence of the virus in both subcellular compartments. Our observations suggest that saliva cells, lymphocytes and epithelial cells, may potentially participate in oral transmission of HTLV-I.

Levels of serum interleukin-1 beta (IL-1 beta) and soluble interleukin-2 receptor (sIL-2R) were assessed in 19 male patients with combat-related posttraumatic stress disorder (PTSD) in comparison to 19 age- and sex-matched healthy volunteers. Serum IL-1 beta levels (but not sIL-2R) were significantly higher (p.001) in the PTSD patients than in the controls. IL-1 beta levels did not correlate with cortisol levels, severity of PTSD, anxiety, depressive symptoms, or alexithymia score; however, they did correlate significantly (r = .54, p.005) with the duration of PTSD symptoms. It is possible that desensitization of the hypothalamic-pituitary-adrenal axis in chronic PTSD patients counteracts the stimulatory effect of IL-1 beta on cortisol secretion.

Human T-cell lymphotrophic virus type I (HTLV-I), is a member of the oncogenic retroviruses family endemic in several parts of the world and also recently identified in the Jewish Mashhadi population who immigrated from Iran to Israel. The virus is the causative agent of adult T-cell leukemia (ATL) and a chronic myelopathy known both as tropical spastic paraparesis (TSP) or HTLV-I associated myelopathy (HAM). The known modes of HTLV-I transmission are by sexual intercourse, from mother to child in breast milk, via blood transfusion, and by sharing of needles by parenteral drug users. In the present study we examined the presence of HTLV-I provirus genomic DNA by nested polymerase chain reaction (PCR) and by DNA hybridization in mouthwash samples obtained from 13 Mashhadi-born Iranian Jews with spastic paraparesis associated with HTLV-I, 4 Mashhadi-born Iranian Jews asymptomatic carriers for HTLV-I and 21 healthy controls. Proviral HTLV-I DNA was detected by mouthwash PCR in 12 of 17 HTLV-I infected subjects (71%) but in none of 21 controls. Proviral DNA was also detected in mouthwash samples using HTLV-I probe by dot blot hybridization assay. The presence of HTLV-I proviral DNA in whole saliva may suggest a possible transmission of the virus via saliva and explain the increased rate of infection in elderly Mashhadi-Jewish population.

Soluble interleukin 2 receptor (SIL-2R) and interleukin 1-B (IL-1B) levels in peripheral blood were assayed by enzyme-linked immunoabsorbent method in 25 patients with Behçet's disease and in 20 healthy controls. Eighteen patients suffered from active Behçet's disease and 6 patients had severe disease manifestations. SIL-2R levels were followed for a period of 16 months and were correlated with disease activity. In all the patients with Behçet's disease the levels of SIL-2R and IL-1B were significantly higher than their control, 958 +/- 712 vs. 404 +/- 119 u/ml (P0.001) for SIL-2R and 639 +/- 741 vs. 59 +/- 53 pg/ml (P0.001) for IL-1B. No correlation was found between disease activity and severity and the levels of SIL-2R and IL-1B. It is suggested that levels of SIL-2R and IL-1B are elevated in patients with Behçet's disease but do not serve as disease activity markers.

Sixty-two specimens of seminal plasma obtained from normozoospermic, oligozoospermic, azoospermic, and immunologically infertile males were investigated. The levels of spermine, basal aldehyde, and aldehyde oxidation products were measured, as was the immunosuppressive activity of seminal plasma. No immunosuppressive activity was found in the immunologically infertile group; all other groups showed immunosuppressive activity. The immunologically infertile males showed low aldehyde oxidation products.

Background Inflammatory reactions have an important part in atherosclerosis. Smooth muscle cells, endothelial cells, monocytes, and T lymphocytes are actively involved. The purpose of this study was to assess whether T lymphocytes are activated in patients with stable angina pectoris who are candidates for a percutaneous transluminal coronary angioplasty (PTCA) and the influence of PTCA on this process. Methods and Results Twenty-four patients participated in the study. All were 40- to 60-year-old men, and all but one underwent successful PTCA. Blood samples were taken 1 day before PTCA and 1 week, 1 month, and 2 months after. Two groups of patients were detected: group A, 11 patients who had high levels of soluble interleukin-2 receptor (sIL-2R) before PTCA that decreased toward normal during the follow-up period in most of them; and group B, 13 patients who did not have elevated sIL-2R levels before PTCA and in whom sIL-2R levels did not change after the procedure. Group C consisted of 15 healthy men whose sIL-2R levels were in the normal range (control subjects). Conclusions (1) T lymphocytes are activated in stable angina patients. (2) The level of sIL-2R can be a reliable laboratory marker for follow-up of patients after PTCA, especially those with high sIL-2R levels before the procedure.

Corticosteroids are known to affect the number and function of circulating lymphocytes in humans. The effect of 2 years administration of inhaled budesonide (200 micrograms/day) on the number and function of B and T lymphocytes and T cell subsets was evaluated in 16 young children with severe asthma. The number of T and B cells and T suppressor/cytotoxic cells (CD8 T cell) and T helper/inducer cells (CD4 T cell) before therapy was found to be comparable to the number of cells observed in the healthy control group. Two years administration of inhaled budesonide did not significantly alter the percentage and absolute number of all these cells. The functional activity of T lymphocytes was evaluated by the "local xenogeneic graft versus host reaction" (GVHR). A positive (normal) GVHR was observed in only 5 of the 16 children (31%) in the budesonide group before therapy, compared to 15 of 16 children (94%) in the healthy control group. During the 2 years treatment with inhaled budesonide, the percentage of patients having positive GVHR increased from 31% before therapy to 69% and 77% after 1 and 2 years of therapy (P = 0.05 and 0.02), respectively. The data observed in this study indicate that 2 years administration of inhaled budesonide did not alter the number of B and T lymphocytes and T cell subsets. However, it was associated with improvement in the GVHR function of T cells.

The Mashhadi-Jewish community originating in Iran is a closed and ethnically segregated population with a unique history and a high rate of intrafamilial marriage among its members. A high risk of infection by human T-lymphotropic virus type I (HTLV-I) and of adult T-cell leukemia associated with such infection was found in this population. HTLV-I is also associated with a syndrome of progressive spastic paraparesis. We therefore evaluated the occurrence of HTLV-I infection and spastic paraparesis in Mashhadi-born Iranian Jews who immigrated to Israel. We examined 83 Mashhadi-born subjects (52 women, 31 men; mean age, 61 +/- 15.5 years) and 73 age-matched non-Mashhadi Iranian-born Jews. Blood samples were tested for HTLV-I antibodies by particle agglutination test. The polymerase chain reaction (PCR) was used to detect HTLV-I proviral DNA sequences from peripheral blood mononuclear cells. Fifteen Mashhadi-born Jews (18%) were both seropositive and PCR-positive for HTLV-I. Four HTLV-I-seronegative subjects were found to be positive for HTLV-I proviral DNA by PCR. Of the 19 HTLV-I-infected subjects (11 women, 8 men; mean age, 59 +/- 16 years), 13 (68%) had spastic paraparesis of varying severity. There were no signs of myelopathy in the Mashhadi-born subjects who were negative for HTLV-I proviral DNA by PCR. None of the non-Mashhadi Iranian Jews was seropositive or PCR-positive for HTLV-I proviral DNA, or had clinical signs of spastic paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Peripheral blood lymphocytes were obtained from eight untreated patients suffering from long-standing plaque-type psoriasis 1 h following UVB treatment and at the end of 15 UVB treatments. Before treatment and following in vivo treatment with 0.01-0.3 J/cm2, the patients' lymphocytes were tested for interleukin-2 (IL-2) production, and helper activity with and without addition of the immunomodulator AS101. AS101 is a synthetic organotellurium compound, ammonium trichloro-(O,O'-dioxyethylene) tellurate. UVB at a flow of 0.01 J/cm2 did not affect any of these functions. However, after 15 UVB treatments, when the dose given had reached 0.3 J/cm2, a complete inhibition of IL-2 production and helper activity was observed. In vitro addition of AS101 at 0.1 micrograms/ml to the in vivo UVB-treated lymphocytes raised IL-2 production to approximately double the initial level, and improved the helper activity of CD4 cells.

Multiple parameters of immune function were measured serially before and one and five weeks following operation in 14 patients with fibrocystic disease of the breast (Group A) and in 20 patients with stage 1-2 infiltrating duct carcinoma (Group B). These parameters included the following: WBC, total number and percentage of lymphocytes, numbers of B cells, T cells, T-active, T-helper and T-suppressor cells and the ratio between the latter as well as spontaneous suppressor or helper activity and the graft-versus-host reaction. Prior to operation no statistically significant difference was found between the two groups except for the number of T-helper cells, which was higher in Group B (p less than 0.05), and the spontaneous suppressor activity, which was higher in Group B (p less than 0.05). The finding of such a high percentage (80%) of negative graft-versus-host reactions five weeks after operation together with the high suppressor activity may indicate the presence of tumor micrometastases. The burden of surgery and general anesthesia was stronger in Group B, with a pronounced difference found between the groups (p = 0.0005), but the interaction between the influence of time (surgery and anesthesia) and the groups was not as great (p = 0.4864) and was found to be different for each group.

This study tested the immunomodulatory effects of AS101, a synthetic organotellurium compound, on interleukin (IL-2) production and functional activity of normal human lymphocytes. Normal human lymphocytes were treated in vitro with 8-methoxypsoralen alone, ultraviolet A (UVA) and psoralen plus UVA (PUVA) as well as with a combination of AS101 + phytohaemagglutinin (PHA)+phorbol myristate acetate (PMA) and the above-mentioned treatments. Following treatment IL-2 production, free IL-2 receptor (IL-2R), the ability of lymphocytes to induce a local graft-versus-host reaction (GVHR) and the ability of separated CD4 cells to induce help were tested. 8-Methoxypsoralen alone did not significantly affect either cell proliferation or IL-2 production or functional activity. However, UVA and PUVA had a high inhibitory effect on cell proliferation, IL-2 production, IL-2R release and the functional activity of T- and T-helper lymphocytes. In the present study, the addition of AS101 and PMA serve to restore the impaired IL-2 production, T- and T-helper lymphocyte functional activity, but not the IL-2R release. AS101 alone without PMA was also effective in restoring GVHR and helper activity of CD4 lymphocytes, without affecting cell proliferation.

A possible cause for implantation failure following embryo transfer is the rejection of pre-embryos by the maternal immune system. To elucidate the mechanisms underlying the rescue of the pre-embryo from maternal rejection, immunosuppressive activity was investigated in culture media containing human oocytes fertilized in vitro by employing the graft-versus-host reaction and the active rosette test. Normal donor lymphocytes were incubated with culture medium containing either fertilized or nonfertilized oocytes. Control experiments were carried out using lymphocytes incubated in culture medium only, as well as in culture medium containing human sperm. In 67% of the tests (12 out of 18), graft-versus-host reaction was inhibited, as compared to 29% of those performed with medium in which oocytes failed to fertilize (p less than .03), and 33% with medium in which only sperm was present. The frequency of an inhibitory active rosette test was similar in both groups. It is possible that immunosuppressive properties are acquired by the human pre-embryo as it grows in culture. Detection of such substances, which could contribute to the establishment of pregnancy, may improve monitoring of embryo quality prior to transfer.

Seventy patients with Duke's C adenocarcinoma scheduled to undergo operation were divided into two groups, those who received no perioperative transfusion (Group I, 26 patients) and those who received an average of 2.1 units per person of packed red blood cells perioperatively (Group II, 44 patients). Immunological parameters were tested before and one and five weeks after the operation in order to determine the influence of the transfusion on these parameters as well as that of the site of the tumor, whether right colon, left colon or rectum. Comparison of the mean values obtained before operation with those obtained one week post-operatively revealed a significant change in the number of B cells (p = 0.014), with a decrease in Group I and a rise in Group II, which was seen to persist for the mean values obtained five weeks after operation. The higher rates of recurrency and lower rates of survival reported in patients who received transfusion may be related to an as yet unidentified role of B cells or a subpopulation in the immune system, manifested in the suppression of activity of those components responsible for destroying micrometastases. In relation to the site of the tumor no definite conclusions can yet be drawn as to the prognostic importance of our findings concerning the immunological parameters.

Seventy patients with Duke's C adenocarcinoma scheduled to undergo surgery were divided into two groups, those who received no peri-operative transfusion (Group I, 26 patients) and those who received an average of 2.1 units of packed red blood cells per person peri-operatively (Group II, 44 patients). Immunological parameters were tested 1 week before and 1 and 5 weeks after surgery in order to determine the influence of the transfusion of these parameters. Comparison of the mean values obtained before operation with those obtained one week post-operatively revealed a significant change in the number of B cells (P = 0.014), with a decrease in Group I and an increase in Group II, which was seen to persist for the mean values obtained 5 weeks after surgery. The higher rates of recurrence and the lower rates of survival reported in patients who received transfusion may be related to an as yet unidentified role of B cells or a subpopulation in the immune system, manifested in the suppression of activity of those components responsible for destroying micrometastases. In relation to the site of the tumor no definite conclusions can yet be drawn as to the prognostic importance of our findings concerning the immunological parameters.

Seventy specimens of human seminal plasma obtained from azo-ospermic, oligospermic, and normospermic men were tested for immunosuppressive activity on normal donor lymphocytes. Spermine and spermidine levels in acidic extracts were determined in 32 specimens of seminal plasma from the three groups. The original seminal plasma as well as the neutralized spermine extracts were examined for their effect on the functional activity of the lymphocytes. Seminal plasma obtained from the normospermic and oligospermic semen showed significant immunosuppressive activity, whereas no immunosuppressive activity was induced by seminal plasma from azo-ospermic semen. The latter finding was in accordance with the low spermine levels in azo-ospermic semen, which were about 50% of those found in normospermic and oligospermic seman. Acidic extraction of the seminal plasma of azo-ospermic origin resulted in an increase in spermine levels and also in immunosuppressive activity, demonstrating that in azo-ospermic men spermine is bound probably to a protein and is released after acidification, exerting its immunosuppressive activity only when unbound.

Preterm delivery is a major obstetric and public health problem, accounting for 50-70% of all perinatal deaths. An enzyme-linked immunoassay (ELISA) test was used to determine serum interleukin 1b (IL-1b) levels in 32 women with preterm contractions compared with 26 women in term labour and 11 normal preterm pregnant women. Women with preterm contractions (with or without treatment) had significantly lower mean serum levels of IL-1b (23.5 pgr/ml) compared with women in term labour (218 +/- 57 pgr/ml), but similar levels to pregnant women not in labour at the same weeks of gestation.

Jaundice with evidence of hepatocellular damage of moderate severity was observed in a patient who received methyldopa. The diffuse mononuclear infiltration of the liver tissue was found to consist of 90% E-rosette-forming cells. Peripheral lymphocytes gave a markedly positive macrophage migration inhibition (MIF) test against methyldopa. The number of T lymphocytes in the peripheral blood was at the lower limit of normal but they proved to be functionally inactive, as demonstrated by the results of a local xenogeneic graft-vs-host reaction test. The liver disease was associated with hyperglobulinemia, a decrease of the third and fourth components of complement and the presence of incomplete erythrocytic antibodies, leukoagglutinins, antinuclear factor, and smooth muscle antibody. Follow-up after discontinuation of the drug revealed a gradual return to normal of liver function and MIF tests, normalization of cellular immunity, and disappearance of the humoral antibodies. It is assumed that sensitization by methyldopa triggered the autoaggressive phenomena and their ultimate manifestation in the liver.

A 33-year-old male of proven fertility suffered six attacks of malaria while resident in an African country. For this he received anti-malarial drugs. Semen analysis performed after the fourth attack, and repeated during the following 2 years after his return to Israel, revealed severe oligozoospermia, necrozoospermia and occasionally even azoospermia. Immunological examination of the patient revealed an inverse ratio of T-cell subsets and mast cell degranulation in response to palludrin. Twenty-five months after the last attack of malaria a significant improvement was found in semen quality and there was an increase in the ratio of T-helper to T-suppressor cytotoxic cells. These observations indicate that although malaria and its treatment may affect spermatogenesis, recovery may be expected eventually.

The activity of adenosine deaminase (ADA) was measured in thymus and spleen subpopulations separated by peanut agglutinin (PNA) of melanoma B-16 C57BL bearing mice and normal age-matched C57BL mice. Groups of 10 mice were used each time and the experiments were repeated 6 times. The adenosine deaminase activity in the PNA+ thymocytes of B-16 bearing mice was about 2.5 times lower than that of the normal C57BL mice while the ADA activity in the PNA+ fraction of spleen of the B-16 melanoma bearing mice was 2.5 times higher. These results demonstrate that the tumor burden probably induces a different redistribution and traffic of lymphocytes from one lymphopoietic organ to another. This traffic can also explain the thymus involution and spleen enlargement found in the B-16 mice.

Peripheral blood B and T lymphocytes were studied in 100 patients with polycythemia vera (PV), in whom no immunoglobulin abnormalities were detected. A significant decrease of the total lymphocyte count as well as of the relative and absolute values of B- and T-cell count was found. These results were unaffected by the modality of treatment, i.e., repeated phlebotomies or 32 P. However, in 28.8% of the PV patients a negative graft-versus-host reaction was found. This finding was significantly higher among the 32 P-treated PV patients (46.6%), when compared to the phlebotomy-treated ones (25.3%), suggesting possible reduced immuno competence in the 32 P-treated patients.

Chronic generalized trichophytosis in a 44-year-old female is reported. The disease began when she was 15 and gradually spread from the scalp. Surviving hairs on the scalp and eye-brows showed an endothrix invasion. Enlargement and fistulization of the cervical and axillary lymph nodes were also present. Trichophyton schoenleinii was cultured from the scalp while Trichophyton violaceum was isolated from the body skin, the nails and lymph nodes. Griseofulvin produced significant improvement with occasional relapses. The possible role of the basic cell-mediated immune defect, as revealed by the decreased number of the T and B cells, is discussed.