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The expression of HLA class I antigens was studied using the immunoperoxidase technique on 30 patients with prostate cancer and 29 patients with benign prostatic hypertrophy (BPH). Forty-three percent of the tumors stained positive, in contrast to 21% of the BPH. An inverse relationship was noted between class I expression and degree of tumor differentiation: 88% of the well-differentiated tumors (8/9) expressed class I antigen, compared with 33% (3/9) of the moderately differentiated and 16% (2/12) of the poorly differentiated tumors. No significant survival difference was found between those with class I-positive and -negative tumors. However, when both class I expression and degree of differentiation were considered, those with positive tumors at each level of differentiation had better survival than those with negative tumors. These data suggest that HLA class I expression may serve as a finite prognostic factor and may have relevance in future immunotherapy.

The purpose of this study was to determine the relationship between C-reactive protein (CRP) levels and intraamniotic infection in 48 women presenting with preterm labor and intact membranes. Blood samples for CRP tests were obtained immediately before the performance of transabdominal amniocentesis. The prevalence of amniotic fluid cultures positive for organisms was 14.6%. In 16 women (33.3%) positive CRP levels were obtained. There were no significant differences in the prematurity rate or the prevalence of microbial invasion of the amniotic cavity between women with positive CRP levels and women with negative levels. The sensitivity, specificity, and positive and negative predictive values for the detection of amniotic infection were 71.5%, 73.2%, 31.3% and 93.8%, respectively. Based on these results, we suggest that in women with preterm labor and negative CRP levels, routine amniocentesis may not be essential to the initial workup.

We report 2 cases of a pityriasis rosea-like eruption after the use of the anti-inflammatory and antipyretic medications naproxen, acetaminophen, and a combination of acetylsalicylic acid and codeine phosphate. The role of these drugs in the induction of the eruption was supported by the results of macrophage migration inhibition factor and mast cell degranulation tests performed on the offending drugs.

There is a strong association between systemic and intrauterine infection and preterm delivery. C-reactive protein (CRP) is considered a nonspecific marker for intrauterine inflammation. We determined its blood level in 100 women who presented with preterm labor and intact membranes and delivered prematurely. CRP levels were used as a noninvasive marker for infection to compare clinical characteristics between women who delivered prematurely at 31-36 and 24-30 weeks of gestation. Women who delivered earlier than the 24th week of gestation had a higher rate of positive CRP levels than those who delivered later, 54% vs 24%, respectively (p0.0001). Moreover, women from the lower gestational age group with positive CRP levels had significantly different clinical characteristics than those in the same group but with negative CRP levels. There was a significant difference between Jewish and Bedouin women in cervical dilatation and time interval from hospitalization to delivery between those with positive CRP and those with negative CRP levels. We conclude that patients who delivered prematurely at 24-30 weeks had higher rates of an inflammatory etiology than women who also delivered prematurely, but at a more advanced gestational age.

The expression of class I histocompatibility antigens (HLA) in transitional cell carcinoma of the bladder was studied by the immunoperoxidase technique and correlated with tumor differentiation and survival. Tumors of 33 patients who underwent cystectomy were examined; 57% of the tumors expressed HLA class I antigens. Positive expression was observed in 5 of 6 cases with Grade 1 tumors, 8 of 13 with Grade 2, and 6 of 14 with Grade 3. The 5-year survival was significantly better in patients with HLA class I-positive tumors (74%) compared with those with negative tumors (36%, P less than 0.05). The expression of HLA class I on tumor cells may serve as a target for the immune response and control the metastatic potential of the tumor. These results suggest that HLA class I expression in bladder carcinoma is a prognostic indicator that should be considered in treatment planning.

Sera of 16 patients with systemic lupus erythematosus (SLE) and active involvement of the CNS were examined for the presence of antibodies to human brain neurons, using indirect immunofluorescence of human brain tissue sections. Thirteen of the 16 patients (81%) had high antineuronal titers, which declined during convalescence, compared with 18 of 105 (17%) SLE patients who had no CNS disease. Competition assays showed that the binding of the antineuronal antibodies was blocked by mycobacterial glycolipids and bovine brain extracts. This finding suggests an additional link between mycobacterial infection and SLE.

The expression of HLA class I antigens was tested on biopsy specimens originating from 90 patients suffering from adenocarcinoma of the colon. Three different samples were examined from each specimen: one from the tumor and the other two from the neighboring surrounding surgical margins. Twenty-seven out of 27 well-differentiated carcinomas were found highly positive for the presence of HLA class I antigens. Most of the moderately well differentiated tumors (37 out of 46) were weakly positive. None of the poorly differentiated tumors (n = 11) nor the mucin-producing tumors (n = 6) expressed HLA class I antigens. In 180 histologically normal colonic epithelia from patients suffering from adenocarcinoma of the colon (surgical edges free from tumorous tissue of the same specimens) no positive expressions were found. These results tend to suggest that class I HLA-ABC deficient, poorly differentiated tumors may possibly evade lethal immune aggression by HLA-restricted cytotoxic T cells and thus progress to overt malignancy. This negative expression may provide an explanation for the poorer prognosis observed among patients afflicted by a poorly differentiated adenocarcinoma or mucin-producing adenocarcinoma of the colon. Furthermore, these results tend to suggest that enhanced expression of HLA class I antigens on colonic epithelium could serve as a clinical laboratory indication for further examination looking for the possible emergence of neoplasm. If further verified, this may prove to serve as a predictive diagnostic tool for screening populations at risk.

An experimental and a clinical study were performed in order to investigate the liver changes and immunological disturbances that follow a burn injury. The possibility of an autoimmune reaction, initiated by autoantigens or mitogens released from the burn eschar, is discussed, in relation to the results of the clinical and experimental study.

Opsoclonus and other cerebellar symptomatology developed in a patient who underwent mastectomy for adenocarcinoma of the breast. No evidence for metastases was found. Immunological studies demonstrated decreased function of T suppressor cells and hyperreactivity of T helper cells in spite of a normal suppressor/ helper ratio. The clinical condition, as well as the immunological abnormalities normalized under steroid treatment. An autoimmune process as etiopathogenesis of this paraneoplastic syndrome is proposed.

Asthmatic patients have a deficiency of concanavalin A-(Con A) induced suppressor cell function. We tested whether oral colchicine 0.5 mg twice daily for 7 days could correct this immunoregulatory abnormality. Peripheral blood mononuclear cells were incubated with Con A and then suppression of proliferation was measured by coculture of these cells with healthy volunteers' mononuclear cells and phytohaemagglutinin. Sixteen asthmatic patients had significantly (P less than 0.002) decreased Con A-induced suppressor cell function (17.0 +/- 17.2%, mean +/- s.d.) as compared to 13 healthy volunteers (37.9 +/- 14.9%). Oral colchicine significantly (P less than 0.05) increased, though only partially corrected, these 16 asthmatic patients' Con A-induced suppressor cell function (28.1 +/- 14.3%). Asthmatic patients had an increased number of monocytes (691 +/- 289 vs 388 +/- 271/mm3 for normals, P less than 0.01) and a normal number of lymphocytes, Leu 4+ total T cells, Leu 3+ helper/inducer T cells, and Leu 2+ suppressor/cytotoxic T cells as well as a normal Leu 3/Leu 2 ratio. Oral colchicine significantly (P less than 0.005) decreased the number of monocytes (451 +/- 255/mm3) without significantly affecting the number of lymphocytes, Leu 4+, Leu 3+, or Leu 2+ T cells, or the Leu 3/Leu 2 ratio. These results are consistent with the hypothesis that the deficiency of Con A-induced suppressor cell function in asthmatic patients may be due, in part, to an increased number and/or abnormal activity of monocytes. If so, then oral colchicine may have partially corrected the deficiency of Con A-induced suppressor cell function by decreasing the number and/or modulating the activity of monocytes.

Organ culture of xenogeneic thyroids leads to a prolonged survival time. This effect can be reversed when donor-specific cells are injected at the time of transplantation. The results of this experiment disprove the assumption that target antigens are modulated or masked by organ culture.

Defective suppressor cell function has been demonstrated in several diseases but has not been tested in familial Mediterranean fever (FMF). We tested the ability of concanavalin A-activated suppressor cells from one family with FMF to inhibit the proliferation of phytohaemagglutinin-stimulated responder cells from normal volunteers. Four FMF patients tested between acute attacks had a mean (+/- s.e.) per cent suppression (5 +/- 2) which was significantly (P less than 0.0005) less than an FMF patient tested during a spontaneous remission (47 +/- 3), 10 healthy family members (41 +/- 6) and eight normal volunteers (45 +/- 4). Since FMF is inherited as an autosomal recessive disorder, deficient suppressor cell function is expressed in homozygotes between acute attacks, but not in a homozygote in spontaneous remission, homozygotes who are phenotypically normal, nor heterozygotes. This suggests that the suppressor cell abnormality in this family is probably related to the pathogenesis of FMF rather than representing a genetic marker of FMF or non-specific depression by disease activity.

We have previously reported that three patients with familial Mediterranean fever (FMF) had deficient concanavalin A (Con A) activated suppressor cell inhibition of the proliferation of healthy volunteers' phytohaemagglutinin stimulated responder cells. When these three FMF patients were treated with long term oral colchicine (2 mg/day), their Con A activated suppressor cell deficiency was corrected and FMF attacks prevented. In the present report, the effect of in vitro as well as in vivo colchicine treatment on the suppressor cell function of these three FMF patients as well as one more FMF patient was tested to determine whether colchicine can directly increase suppressor cell function rather than colchicine's preventing FMF attacks by unknown mechanisms which only indirectly results in a correction of the suppressor cell deficiency. Long term oral colchicine treatment corrected the suppressor cell deficiency in the four FMF patients (5±2%, 35±5%, and 46±4% for mean ±s.e.m.% suppression for 0, 1 and 2 mg/day of oral colchicine, respectively). Oral colchicine treatment corrected their suppressor cell deficiency within one week of commencing treatment and even corrected one of the FMF patient's suppressor cell deficiency while he still had some FMF attacks on 1 mg/day of colchicine. Suppressor cells from two of the in vivo untreated FMF patients cultured with 10-5 M colchicine plus Con A significantly (P

A method is described for the consistent in vitro generation cytotoxic cells by incubating Fischer 344 rat spleen cells on monolayers of a syngeneic mammary adenocarcinoma. Significant cytotoxicity by in vitro culture is generated as early as 3 days after initiation and effector cells are cytolytic only toward target cells of the sensitizing monolayer. Reciprocal sensitization with allogeneic fibroblasts as the immunizing monolayer yielded effector cells cytolytic for the fibroblasts but without effect on the mammary tumor. The consistency in the generation of cytotoxic cells by in vitro culture should permit its standardized use in following other related immune phenomena such as blocking by serologic factors and suppression, recritment of memory for cytotoxic function.

Durch die Theorie der allogenen Interaktion wird postuliert, das die klassischen serologisch definierten Antigene (SD) allein nicht in der Lage sind, die Immunantwort gegen ein Organtransplantat zu induzieren. Hinweise fur die Richtigkeit dieser Theorie sind: 1. Nicht-lymphoide Zellen stimulieren in der gemischten Lymphocytenkultur (MLC) nicht oder nur gering. 2. Behandlung von lymphoiden Zellen mit UV-Strahlen oder Hitze eliminiert ihre Fahigkeit zur Stimulation, obwohl die SD-Antigene intakt bleiben. 3. In geeigneten Kombinationen kommt es in der MLC zu einer starken Proliferation zwischen SD-identischen Zellen. 4. Gereinigte SD-Antigene in loslicher Form stimulieren Lymphocyten nicht.

A recently described in vitro test for cow's milk protein hypersensitivity was applied to adult patients with ulcerative colitis. The test system involved the culture of their peripheral blood lymphocytes with and without beta-lactoglobulin, and the results were expressed as a stimulation index. Stimulation with beta-lactoglobulin was significantly higher (P less than 0.02) in patients with active disease than in those with inactive disease or in healthy controls. beta-Lactoglobulin was the only one of four cow's milk proteins that showed this effect. It is concluded that the cow's milk protein beta-lactoglobulin has a specific blastogenic effect on the lymphocytes of patients with active ulcerative colitis, and, therefore, may serve as a marker of disease activity.

The effect of colchicine on immunoregulatory T lymphocytes in children with familial Mediterranean fever (FMF) was studied. Concanavalin A (Con A)-induced suppressor cell function was significantly (P less than 0.0001) decreased in five untreated FMF patients (15 +/- 3%, mean +/- s.e.) as compared to six age matched paediatric controls (46 +/- 3%) and eight healthy adults (49 +/- 4%). When the five untreated FMF patients' mononuclear cells were pre-incubated in vitro with Con A plus 10(-5) M colchicine, their suppressor cell function was significantly increased (52 +/- 10%, P less than 0.01). Similarly, oral colchicine treatment (0.5 mg twice daily) significantly (P = 0.02) increased the five FMF patients' Con A-induced suppressor cell function to levels (34 +/- 6%) that were not significantly (P greater than 0.05) different than the paediatric controls or the healthy adults. The percentage of OKT8+ cells (but not OKT3+ or OKT4+ cells) was significantly (P less than 0.0001) decreased in 10 untreated FMF patients (16.0 +/- 0.9) as compared to 10 paediatric controls (27.6 +/- 2) or 10 healthy adults (25.7 +/- 0.6). The 10 untreated FMF patients had a significant (P less than 0.002) increase in the OKT4/OKT8 ratio (2.41 +/- 0.13) as compared to 10 FMF patients treated with 0.5 mg twice daily of colchicine (1.81 +/- 0.08), 10 pediatric controls (1.47 +/- 0.2), or 10 healthy adults (1.78 +/- 0.11). Colchicine appears to have corrected the FMF patients' elevated OKT4/OKT8 ratio by both decreasing the percentage of OKT4+ cells and increasing (but only partially correcting) the percentage of OKT8+ cells. Thus FMF patients have a suppressor cell deficiency in which colchicine treatment corrects their deficiency of Con A-induced suppressor cell function and their elevated OKT4/OKT8 ratio. This raises the possibility that colchicine might be potentially useful as an immunomodulating drug in treating patients with autoimmune or allergic diseases associated with a suppressor cell deficiency.

Measurement of the development of cytolytic activity by mammary tumor primed or unprimed syngeneic spleen cells on in vitro monolayers of the 13762 rat mammary tumor operationally defined several subpopulations of lymphoid cells involved in the cytotoxic response. In vitro sensitization of cells from Fischer 344 animals injected 2 to 10 days earlier with 2 x 10(7) viable tumor cells always resulted in a higher and earlier lytic response than cells from non-inoculated animals. Adoptive transfer of the same in vivo primed cells for 5 days in irradiated syngeneic hosts removed any cytotoxic cells originally present but subsequent in vitro sensitization still resulted in a higher and earlier cytolytic response. We defined such cells as "memory" cells for cytotoxicity. Memory cells were radiosensitive and specific for the immunizing target cell. In contrast to cells from animals inoculated for 3 to 10 days, cells obtained 11 and 12 days after immunization had a lower response than unprimed cells on vitro sensitization. The anamnestic response could be restored either by culturing 12-day primed cells in vitro for 2 days without antigen or by adoptive transfer for 5 days into irradiated syngeneic rats. This suggests that another population of cells is present in spleen and suppresses the conversion of memory to cytotoxic cells. A more direct measurement of suppressor cell function was obtained by coincubating tumor-primed and unprimed cells on monolayers during in vitro sensitization. Cells from animals bearing tumors for 5 to 10 days always caused an increase in the response of the mixed lymphocyte groups, whereas 11- to 13-day tumor primed cells always caused a marked decrease in the cytolytic response. These results suggest the following interpretation of the kinetics of cell-mediated cytotoxicity to syngeneic tumor inoculation. Cytotoxic cells appear about 6 days after immunization, reach peak levels 2 days later, and then decrease rapidly. Memory cells are generated at a faster rate, reach peak levels before maximum cytolytic activity, but are then functionally inhibited from converting into differentiated cytotoxic cells by a new population of suppressor cells which reach peak activity about 12 days after immunization.

We have previously reported a suppressor cell deficiency in four patients with familial Mediterranean fever (FMF). Since colchicine prevents FMF attacks, we tested the effect of colchicine (1 mg twice daily) on the suppressor cell function in three of these FMF patients. Proliferation of phytohaemagglutinin-stimulated responder cells co-cultured with concanavalin A-induced suppressor cells was measured. The three FMF patients' means (+/- s.e.m.) percentage suppression of normal responder cells was markedly low before treatment (6 +/- 2) but significantly (P less than 0.001) increased during colchicine treatment (41 +/- 5) to levels similar to normal volunteers' mean percentage suppression (44 +/- 3). Colchicine corrected their suppressor cell deficiency and prevented FMF attacks during the 15 months of treatment. These findings support the hypothesis that there may be an association between these three patients' suppressor cell deficiency and the pathogenesis of their disease. Furthermore, colchicine may be potentially useful in treating patients with other diseases associated with a suppressor cell deficiency.

The rat mammary adenocarcinoma 13762A is weakly immunogenic in syngeneic hosts. Transplantation immunity is not developed after injection of irradiated tumor cells. Two cell types were isolated from the tumor: one grew slowly forming solid implants; the second grew rapidly in ascites form, even in allogeneic hosts. Spleen cells cytotoxic for a tissue culture derivative of the tumor were produced in animals after injection of either cell type indicating a common antigen. The kinetics of tumor growth and production of cytotoxic spleen cells were compared in syngeneic and allogeneic animals. In vivo rejection of the tumor in allogeneic hosts did not correlate with the in vitro assay of spleen lymphocyte cytotoxicity. Futhermore, the cytotoxic response of spleen cells from syngeneic tumor-bearing hosts parallels that found in allogeneic hosts.

Summary The suppressor cell activity of peripheral blood lymphocytes was investigated in wheezy children by determining the ability of concanavalin A induced suppressor cells to inhibit a mitogen provoked proliferative response. The activity was compared with that of eighteen healthy controls. Often infants aged from 5 months to 4½ years, with recurrent wheezy bronchitis, three had much reduced suppressor cell activity (2 s.d. or more below that of controls). Of twelve asthmatic children aged from 4½ to 12 years, seven had much reduced suppressor cell activity. The remaining five asthmatic children with normal suppressor cell activity had all received hyposensitization therapy. We speculate that immune hyposensitization therapy might act by stimulating lymphocyte suppressor activity.