Identification of T & B lymphocytes on skin sections from patients with lymphoproliferative disorders of the skin.

The T & B lymphocytes in frozen sections of skin obtained from patients with various lympho-infiltrating disorders of the skin were identified using an immunofluorescent technique. Anti T-lymphocytes serum was used as a T marker and anti Ig GMA serum and HL-B alloantigens as B markers. The method confirmed to be efficient in preliminary experiments. Specimens were obtained from patients with lymphocytic infiltration of the skin (LIS), lymphadenosis benigna cutis (LBC), lymphoma cutis (LC) and mycosis fungoides (MF). In LIS and LBC the dominant cell was found to be the T lymphocyte, suggesting that a local immune reaction of the cell mediated type may play a role in their etiology.

Elevated levels of serum interleukin-1 beta in combat-related posttraumatic stress disorder.

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.

In vitro induction of T suppressor lymphocytes in recipients of renal allografts by THF, a thymic hormone.

Lymphocyte subpopulations were determined in 13 patients, recipients of kidney allografts, 7 of them during an acute rejection episode (ARE). Monitoring of the T lymphocyte suppressor or T helper cells was performed by aid of the theophylline sensitivity test and the local xenogeneic graft-versus-host reaction (GVHR). An absence or a striking decrease of theophylline-sensitive T suppressor cells was found in all patients during ARE. Incubation of the lymphocytes of these patients with a thymic hormone, THF, raised the number of TS lymphocytes from nil or from a very low level to normal or above. The therapeutic use of THF in selected renal allograft recipients is proposed.

Blocking antibodies and T cell subsets in long-term survivors of renal allografts.

Fc-receptor blocking antibodies as well as T cell subsets were studied in a group of 12 long-term survivors of renal allografts. The absolute number of T suppressor cells was similar to that found in a control group, but there was a significant decrease in the total number of T helper lymphocytes and a decreased helper/suppressor ratio. Sera from all patients tested showed inhibitory activity in the erythrocyte antibody model against leukemic B lymphocytes, demonstrating the presence of Fc-receptor blocking antibodies. Also inhibited was the ability of normal human lymphocytes to form E rosettes and to induce a local xenogeneic graft-versus-host reaction. These findings indicate that the Fc blocking antibodies are beneficial to the patient, possibly by abrogating the cellular and humoral immune mechanism that is detrimental to the kidney allograft.

Adenosine deaminase activity in lymphocyte subpopulations of B-16 melanoma and normal C57BL bearing mice.

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.

Excision of epithelial tumors: CO2 laser versus conventional methods.

In a comparative experimental study, excisions of a transplanted Lewis lung carcinoma in BDF1 mice were performed by means of the CO2 laser and conventional methods, namely common scalpel and diathermy. The results showed a significant reduction in tumor recurrence and animal mortality rates (27.5% vs. 75% and 45%) after tumor excision with the laser in the early stage (5th day) of tumor development. This finding, in addition to the surgical properties of the CO2 laser, suggests that early excision using this modality is a rational treatment of this type of tumor.

The effect of withaferin A on human peripheral blood lymphocytes. An electron-microscope study.

Cultures of normal human peripheral blood lymphocytes stimulated by phytohaemagglutinin (PHA) were treated with withaferin A and examined by an electron microscope. The compound was found to affect the spindle microtubules of cells in metaphase. There were no intact pole-to-pole microtubules or pole-to-kinetochore microtubules found in the treated cells; the centrioles were located in the center. Furthermore, cells at interphase were also affected, the membrane system of the cells being damaged.

The effect of withaferin A, a natural steroidal lactone, on the fine structure of S-180 tumor cells.

Mouse sarcoma 180 (S-180) solid and ascites tumor cells were treated in vivo and in vitro with withaferin A and observed with the electron microscope. The compound was found to effect this spindle microtubules of cells in metaphase. An interesting finding was the double membranes surrounding the chromosomes in the treated cells; probably the nuclei were reconstructed directly from the metaphase stage in the in vivo withaferin A-treated cells. In addition the membranes of the cells in interphase were affected by in vivo or in vitro treatment with the compound.

Detection of HTLV type I provirus by in situ polymerase chain reaction in mouthwash mononuclear cells of HAM/TSP patients and HTLV type I carriers.

Molecular studies have revealed the presence of HTLV-I provirus DNA in saliva of HTLV-I-infected subjects. However, cellular localization has not been determined. In the present study, we have used in situ PCR technique to study saliva-associated cells for localization of HTLV-I proviral DNA. We found that HTLV-I proviral DNA was present in the nuclei and cytoplasm of salivary lymphocytes in five (71%) of seven HTLV-I-seropositive subjects. The percentage of infected cells in positive mouthwash samples ranged from 0.5 to 2%. None of the HTLV-I-negative patients had HTLV-I provirus in saliva. The localization of HTLV-I provirus DNA suggests that salivary lymphocytes can serve as vector for HTLV-I infection through saliva.

A mouse ear reaction for assessment of human lymphocyte immunocompetence.

A mouse ear reaction for testing cell mediated immunity of human lymphocytes using the local graft-versus-host reaction assay is described. Five million human mononuclears were locally injected into the ears of immune suppressed NZW mice. The reaction mounted was quantitated by determining the 125I-Iodo-Deoxyuridine (125I-UdR) incorporation in both ears. The ratio of 125I-UdR incorporation, of the injected to that of the non-injected ear (GVHR index), 7 days after lymphocyte injection, served as an accurate measure for the extent of the reaction. Only normal human mononuclears and purified, separated normal human T lymphocytes mounted a local graft-versus-host reaction. Whereas normal human B lymphocytes, chronic lymphatic leukemia B lymphocytes, mononuclears from patients with transitional cell carcinoma of the bladder, irradiated normal human mononuclears, mouse syngeneic mononuclears, or human erythrocytes gave no positive reaction. These experiments demonstrate that this assay can be used to quantitate an in-vivo specific graft-versus-host reaction.

Effect of parathyroid adenoma excision on interleukin-6 (IL-6) and IL-2 receptor levels.

1,25-Dihydroxycholecalciferol [1,25(OH)2D], 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)2D 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 parathyroid adenoma excision on serum IL-2 receptor (IL-2R) levels and the release and production of IL-2R and IL-6 by peripheral blood lymphocytes (each measurement was performed 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.

Mumps orchitis among soldiers: frequency, effect on sperm quality, and sperm antibodies.

This study reports on 72 young soldiers who suffered from a recent epidemic of acute mumps, with special emphasis on 19 who suffered from mumps orchitis and whose spermograms were in the fertility range. The immunological work-up for antibodies in sera or seminal plasma gave normal results for the patients diagnosed with orchitis, as well as the controls. The only remarkable finding was an increased risk of borderline significance for orchitis in smokers. The present study has proven that the presence of antisperm antibodies does not play a role in the etiology of mumps orchitis.

Cellular immune aspects of the human fetal-maternal relationship.

In the present study the number and the function of T lymphocytes obtained from peripheral blood of 35 mothers immediately after delivery and from the cord blood of the respective newborns were tested. Furthermore, the effect of the newborns' lymphocytes on the immunological competence of the mothers' lymphocytes was investigated by means of graft-versus-host-reaction xenograft test. The blood of 14 of the mothers and their newborns was also examined by monoclonal antibodies for determination of T helper and T suppressor lymphocytes. A marked reduction in the absolute number of T helper cells was found in the blood of mothers after delivery. In addition, mothers' lymphocytes manifested a high suppressor activity when added to normal human lymphocytes. It was also found that the cord blood contains lower number and percentage of T suppressor cells. Yet the T cells of the cord blood exert a high suppressor activity on the mother as well as on normal donor lymphocytes. The impaired function of cord blood lymphocytes could be impaired function of cord blood lymphocytes could be restored by in vitro addition of THF, a thymic hormone.

The influence of perioperative transfusions on the immunological profile of patients with colorectal adenocarcinoma.

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.

Lymphocyte subpopulation before and after operation in patients with benign vs malignant breast disease.

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.

Case report. Immunological studies in a case of hepatitis following methyldopa administration.

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.

Screening for Human T-cell Lymphotrophic Virus type-I (HTLV-I) infection in high risk schizophrenic patients.

The Mashhadi-Jewish community originating in Iran is a closed and ethnically segregated population with a unique history and a high rate of intra-familial marriage among its members. High infection rate (23%) by Human T-Lymphotrophic Virus type-I (HTLV-I) was found in this population. 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 infection in high-risk psychiatric patients of Iranian origin in order to evaluate the infection rate in socially isolated subjects. We screened and examined all (N=42) Iranian-born schizophrenic patients in our center, of whom 17 were Mashhadi subjects (7 females, 10 males, mean age 48.7±13.2 years), and 25 were born in Iran in other cities than Mashhad (12 females, 13 males, mean age 43.2±11.9). 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. One Mashhadi-born Jew (5.9%) was seropositive and PCR-positive for HTLV-I. None of the schizophrenic non-Mashhadi Iranian subjects was positive for HTLV-I by either method. This infection rate in schizophrenic patients of Mashhadi origin is significantly lower than rates reported for the normal Mashhadi community. We suggest that the relative isolation imposed by the stigma associated with mental illness and recurrent psychiatric hospitalizations serve to protect this sub-group from HTLV-I infection.