Peripheral Lymphocytes Of Patients Research Articles

Increased sister chromatid exchanges in peripheral lymphocytes of patients with Crohn's disease

A cytogenetic study was performed using Crohn's disease patients to determine whether the presence of chromosome instability is related to Crohn's disease, a chronic inflammatory bowel disease. Sister chromatid exchange (SCE) frequencies in peripheral blood lymphocyte cultures from 22 Crohn's disease patients and an equal number of healthy controls matched for sex and age were analyzed. The mean of SCE frequency in Crohn's disease patients was 11.64±0.42 (SEM) per cell, which was significantly higher than the value of 8.38±0.22 per cell in the matched controls ( p<0.0001). The Crohn's disease patients showed significantly increased high frequency cells (HFC) as compared to those among the matched controls. There was a significant correlation between HFC frequencies of the Crohn's disease patients and the severity of their disease as determined by the number of relapses per year and the degree of chronic activity after adjusting for the smoking status ( r=0.54, p=0.011). In both smokers and non-smokers, the mean SCE and HFC frequencies of the patients were significantly higher than those of the controls. These results suggest that Crohn's disease is a condition with increased chromosome instability characterized by a high level of SCE frequencies which are associated with the inflammatory condition itself.

Calcium Metabolism in Blood and Peritoneal L Ymphocytes from Continuous Ambulatory Peritoneal Dialysis Patients

Cellular immune function in peritoneal dialysis patients has been shown to be depressed, but the mechanism of this immunosuppression has not been ascertained. Because calcium is an important mediator of lymphocyte activation, this study was designed to investigate if there was an alteration of calcium metabolism in the lymphocytes of continuous ambulatory peritoneal dialysis (CAPD) patients. Sixteen CAPD patients were studied at the initiation of CAPD and after two months of treatment. Twenty-three normal controls were also enrolled in the study. Cytoplasmic calcium changes were investigated in response to the mitogen phytohemagglutinin (PHA) in peripheral blood and peritoneal lymphocytes, using the intracellular calcium probe indo-1 and flow cytometry. Baseline cytoplasmic calcium levels and changes in cytoplasmic calcium in response to PHA were assessed at the initiation of CAPD and after two months of therapy. Peripheral lymphocytes of patients and controls had similar calcium baseline levels, but the peritoneal lymphocytes had baseline cytoplasmic calcium levels averaging 81% higher than the corresponding calcium levels of the patients' peripheral blood lymphocytes. As compared to peripheral lymphocytes, the response to PHA stimulation was significantly less in the peritoneal lymphocytes, increasing an average of only 46.8% above baseline. Peripheral blood lymphocytes of the patients responded by an average increase of 78.9% over baseline. Control cells increased an average of 66.3% over baseline. Follow-up studies done two months after the initiation of CAPD indicated there were no significant changes (as compared to month 0) that occurred in baseline or stimulated intracellular calcium concentrations. While the peripheral lymphocytes of CAPD patients respond adequately to PHA, the high baseline calcium levels of the peritoneal lymphocytes suggest that these cells may be in a state of chronic activation and may respond minimally to an antigenic challenge.

Mitogenetic effect of saliva to peripheral lymphocytes in patients with oral cancer and chronic nasopharyngeal infections

Mitogenetic effect of saliva to peripheral lymphocytes in patients with oral cancer and chronic nasopharyngeal infections

Mitogenetic effect of saliva to peripheral lymphocytes in patients with oral cancer and chronic nasopharyngeal infections

Mitogenetic effect of saliva to peripheral lymphocytes in patients with oral cancer and chronic nasopharyngeal infections

High levels of bcl‐2 protein in circulating t lymphocytes, but not b lymphocytes, of patients with systemic lupus erythematosus

Defective regulation of programmed cell death (apoptosis) may play a role in the development of autoimmune diseases, and the proto-oncogene bcl-2 is involved in the control of apoptosis in immunocompetent cells. We therefore wished to investigate the expression of bcl-2 in the peripheral lymphocytes of patients with systemic lupus erythematosus (SLE), a prototypical autoimmune disease. Levels of bcl-2 expression in the lymphocytes of patients with SLE and, for comparison, in the lymphocytes of healthy controls and patients with rheumatoid arthritis (RA), systemic bacterial infections, and chronic B cell lymphocytic leukemia were studied by 2-color cytofluorography and RNA analysis. In SLE patients, a significant proportion of T cells expressed increased amounts of bcl-2 protein. By fluorescence-activated cell sorter analysis, bcl-2--enriched lymphocytes were found in the CD45RO+ as well as in the CD45RO-, and also in the CD4+ and CD8+, lymphocyte subpopulations. Mononuclear cells of patients with SLE showed increased amounts of bcl-2 messenger RNA. An increased percentage of strongly bcl-2 positive peripheral T lymphocytes was found in patients with bacterial infections, but not in those with RA. Although the occurrence of circulating T lymphocytes with abnormally high bcl-2 expression is not specific for SLE, it is evidence for a dysregulation of lymphocytic programmed cell death in this autoimmune disease.

A Study of Production of Interleukin-1α by Peripheral Lymphocytes in Patients with Coronary Artery Disease

A Study of Production of Interleukin-1α by Peripheral Lymphocytes in Patients with Coronary Artery Disease

HOST IMMUNOSUPPRESSION AFTER BLOOD TRANSFUSION AT THE OPERATION FOR GASTRIC CANCER AND AN ATTEMPT OF AUTOGENOUS BLOOD TRANSFUSION

The author measured changes in subsets of peripheral lymphocytes in patients with gastric cancer to observehow the postoperative host immunity is influenced by the transfusion. In the cases without blood transfusion, the CD11(+)CD8(+) cell ratio began to increase at the early time of operation, while the CD4(+)2H4(+) cell ratio decreased. After that, CD11(+)CD8(+) cell ratio returned to preoperative number. CD4(+)2H4(-) cell ratio decreased at the operation and prolonged for a certain period according to the degree of advancement of the disease and operative prceedure. Change of host immunity by blood transfusion performed in addition to surgery was then investigated in 11 stage I+II patients undergoing subtotal resection. Compared with the non-transfusion group, the CD4(+)2H4(-) cell ratio more decreased and the CD11(+)CD8(+) bright cell ratio more increased in the transfusion group, revealing prolonged immunosuppression in the transfusion group. On the other hand, in 17 patients receiving autogenous blood transfusion, CD11(+)CD8(+) bright cell ratio rather suppressed than in the blood transfusion group, and the CD4(+)2H4(-) cell ratio more increased. Although blood transfusion was found to lead to immunosuppressive responce in this study, the use of autogenous blood transfusion eliminated such response.

血清ｇｒｏｕｐ‐ｓｐｅｃｉｆｉｃ ｃｏｍｐｏｎｅｎｔ蛋白と頭皮組織内汗腺にｍｏｓａｉｃｉｓｍを立証した先天性母斑児についての免疫遺伝学的検討

There are two broad categories of chimera: twin and dispermic. Here we report a case of a young girl who was a dispermic chimera and had both group A1 and B red cells in her serum simultaneously.The patient (H. B.) was a five-year old girl with congenital nevus. She was born by normal delivery as the first child of healthy parents. She had nerve received a transfusion, and there was no evidence of a twin. Her blood contained 96% group B, type MNss red cells and 4% group A1, type NNss red cells. The patient's saliva also contained A and B substances at normal secretor ranges. The level of D-galactosaminyltransferase activity in her serum was within the normal ranges but the level of N-acetyl-d-galactosaminyltransferase activity was at the extreme lower end of the normal range for group A1B persons. One hundred metaphase cells from a culture of the patient's peripheral lymphocytes were all 46, XX. The phenotype of the serum group-specific component (GC) protein of the father was GC2-1S, and of the mother, GC2-1F, but the patient's GC protein was GC1S-1F-(-2). This suggests that the patient's serum contained two populations of GC protein. The sweat gland cells of her scalp tissue stained with both anti-A and anti-B reagents.These findings demonstrate this child to be a dispermic chimera according to Race and Sanger's classification system.

Immunocytochemical analysis of blood lymphocytes in uveitis

We studied the surface expression of activation markers IL2-R, HLA-DR and CD45-RO on peripheral T-lymphocytes in two groups of patients (n = 26) with idiopathic uveoretinitis, compared with controls. Thirteen patients were analysed by alkaline phosphatase anti-alkaline phosphatase (APAAP) immunocytochemistry, which demonstrated a significant rise in expression of HLA-DR and IL2-R surface markers. Flow cytometric analysis was performed on a further 13 patients, which confirmed a significant rise in IL2-R expression in uveitis patients. Within this group systemic activation was confined to patients with idiopathic retinal vasculitis. Dual flow cytometry confirmed a CD4+,IL2--R+ T--lymphocyte phenotype. A further 4 patients with retinal vasculitis who had been treated with cyclosporin A demonstrated a 32% reduction in IL2-R expression over a 3-month period. Analysis of CD45-RO and CD5+ cells was found to be uninformative in this study. We have demonstrated activated peripheral lymphocytes in patients predominantly with retinal vasculitis, the significance of which is discussed.

Cyclophosphamide decreases O6-alkylguanine-DNA alkyltransferase activity in peripheral lymphocytes of patients undergoing bone marrow transplantation.

O6-alkylguanine-DNA-alkyltransferase (ATase) levels were measured in extracts of peripheral blood lymphocytes taken at various times during chemotherapy from 19 patients with various haematological malignancies. Seven patients with advanced Hodgkin's disease received preparative treatment consisting of cyclophosphamide (1.5 g m-2, daily) administered on days 1 to 4 and BCNU (600 mg m-2) on day 5 prior to autologous bone marrow rescue (ABMR) delivered on day 7. Treatment in the remaining 12 patients consisted of cyclophosphamide (1.8 g m-2, daily) given on days 1 and 2 followed at day 4 with total body irradiation (TBI) administered in six fractions over the subsequent 3 days to a total dose of 1200 cGy prior to bone marrow transplantation. In the Hodgkin's group, significant decreases in ATase activity were seen during the cyclophosphamide treatment, and the median ATase nadir was 32% (range 0% to 57%) of pretreatment levels following 4 days of cyclophosphamide. In one patient, no ATase activity was detectable following the 4th cyclophosphamide treatment. ATase activities decreased further after BCNU administration to a median of 19% (range 0% to 32%) of pretreatment levels. Extensive cyclophosphamide-induced reduction of lymphocyte ATase levels was also seen in the other group of 12 patients treated with cyclophosphamide/TBI: postcyclophosphamide median ATase nadir was 35% (range 12% to 78%) of the pretreatment levels. No ATase depletion was seen when cyclophosphamide (up to 10 mM) was incubated for 2 h with pure recombinant human ATase in vitro whereas ATase activity was reduced by 90% on preincubation with 100 microns acrolein or with greater than 1 mM phosphoramide mustard. This suggests that a cyclophosphamide-induced decrease in ATase levels in human peripheral lymphocytes in vivo may be due to depletion mediated by the production of intracellular acrolein. Since ATase appears to be a principal mechanism in cellular resistance to the cytotoxic effects of BCNU and related alkylating agents, these observations suggest that a cyclophosphamide-induced reduction in ATase activity may be an additional factor in the effectiveness of the combined sequential therapy.

Lymphokine-activated killer(LAK) Cell Activity and Phenotypic Characterization in Peripheral Lymphocytes of Patients with Cervical Cancer

Lymphokine-activated killer(LAK) Cell Activity and Phenotypic Characterization in Peripheral Lymphocytes of Patients with Cervical Cancer

Cytogenetic characterization of renal cell carcinoma in von Hippel-Lindau syndrome

We report the case of a 26-year-old man with von Hippel-Lindau syndrome (VHL) and two renal cell carcinomas (RCC), one of which was studied cytogenetically. Chromosomal analysis of the RCC showed a translocation that involved chromosomes 3 and 8 with subsequent loss of the derivative chromosome 8. The patient's peripheral lymphocytes showed a normal karyotype that indicated that there was not a constitutional chromosomal translocation. This is the third reported case of RCC in a patient with VHL in which loss of a portion of the short arm of chromosome 3 (3p) has occurred. Similar chromosomal changes that involve 3p have been reported in both familial and sporadic cases of RCC and have led to speculation that a tumor suppressor gene may be located in this region. Cytogenetic characterization of renal tumors could assume increasing significance in the diagnosis and classification of RCC and potentially may guide therapy. These studies may also lead to a better understanding of the biologic behavior of RCC and result in more informed patient evaluation and counseling.

Quantitative and functional restorations and alterations of peripheral lymphocytes in patients with autologous spleen implantation

To reduce the risk of severe infections in splenectomized patients, new methods for splenic preservation or heterotopic autologous spleen implantation have been established. In the latter case, the immunological and functional benefits are still under discussion. In this study we compared immunological parameters in 16 splenectomized patients with and without heterotopic autologous spleen implantation with a nonsplenectomized control group. The total lymphocyte counts--T-cells, CD4+ -, as well as CD8+ - lymphocytes, CD16+ - and B-cells--were highly elevated in both groups, whereby the B-cells were relatively and absolutely higher in the implanted group than in the nonimplanted group. Splenectomized patients had a significantly reduced serum IgM level. The serum IgM of patients with splenic autotransplantation was not significantly lower than that of the controls. In contrast to the impaired in vitro immunoglobulin synthesis in the splenectomized group, the autotransplanted patients showed a normal PWM-induced IgG and IgM synthesis and an increased IgA production compared with the controls. The latter results support the findings of elevated serum IgA levels in this group. The mitogenic-induced proliferation with PHA, ConA, PWM, and OKT3 was not clearly different within the tested groups. The results may indicate a benefit of autologous spleen implantation in regard to the humoral immune response.

Serial Measurement of Sister Chromatid Exchanges in the Peripheral Lymphocytes of Patients with Lung Cancer Receiving Chemotherapy in Relation to Bone Marrow Toxicity

The frequencies of sister chromatid exchanges (SCE) in the peripheral lymphocytes of patients with lung cancer before and after initial chemotherapy were serially measured and the correlation between SCE frequencies and bone marrow toxicity was evaluated. The addition of mitomycin C to vindesine plus cisplatin increased SCE frequencies significantly in patients with non‐small cell lung cancer. A significant increase in frequencies of SCE was observed in patients treated with cyclophosphamide plus adriamycin plus vincristine as compared with those treated with cisplatin plus etoposide in small cell lung cancer. A significant inverse correlation was observed between SCE frequencies in the peripheral lymphocytes 7 days after treatment (x) and the nadir value/pretreatment value of platelets (y)(r= ‐0.685, P= 0.0007, y= 0.842–0.022x). The relation between SCE frequency and leukopenia showed the same trend as thrombocytopenia, but the correlation was not statistically significant (r= ‐ 0.444, P= 0.057). SCE assay may have potential clinical use for the prediction of chemotherapyinduced thrombocytopenia.

Expression of Ley antigen in human immunodeficiency virus-infected human T cell lines and in peripheral lymphocytes of patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC).

Ley determinant (Fuc alpha 1----2Gal beta 1----4[Fuc alpha 1----3]GlcNAc beta 1----R) defined by mAb BM-1 is highly expressed in human immunodeficiency virus (HIV)-infected T cell lines and in CD3+ peripheral mature T cells of patients with acquired immune deficiency syndrome (AIDS) or with AIDS-related complex (ARC). Ley expression increased greatly in the CD3+ population in the advanced stage of AIDS when the CD4+ population decreased greatly. Six other carbohydrate antigens tested by their respective mAbs were not detected in these same cells. None of the carbohydrate antigens tested by the seven mAbs used in this study were found in noninfected T cell lines and in normal peripheral blood lymphocytes.

Effects of PSK on interleukin-2 production by peripheral lymphocytes of patients with advanced ovarian carcinoma during chemotherapy.

The effects of PSK on OKT 4/OKT 8 cell ratio, interleukin‐2 (IL‐2) production and expression of IL‐2 receptor were examined in peripheral blood lymphocytes (PBL) from patients with advanced ovarian cancer during the course of chemotherapy. Preoperative levels of OKT 4/OKT 8 cell ratio and IL‐2 production in PBL from patients with advanced ovarian cancer were significantly lower than those in cases of benign ovarian tumor. However, the expression of IL‐2 receptor did not show any significant difference between ovarian cancer and benign ovarian tumor patients. When a combination chemotherapy of cisplatin, adriamycin and cyclophosphamide was given, the OKT 4/OKT 8 cell ratio was significantly increased with a significant decrease of the absolute number of the OKT 8 cell subset, while the expression of IL‐2 receptor and the absolute number of the OKT 4 cell subset remained unchanged. In contrast, the IL‐2 production was markedly depressed after the first course of chemotherapy. When PSK was combined with combination chemotherapy, the degree of inhibition of IL‐2 production was reduced (though the effect was not statistically significant). If treatment with PSK was initiated after completion of combination chemotherapy, in addition to a significant elevation of OKT 4/OKT 8 cell ratio the depressed IL‐2 production was restored to benign control levels. On the other hand, the expression of IL‐2 receptor remained unchanged even if PSK was given after completion of chemotherapy.

Cytogenetic effects of multiagent chemotherapy on the peripheral lymphocytes of patients with small cell lung cancer

Peripheral lymphocytes of 8 patients with small cell lung cancer (SCLC), who received combination chemotherapy consisting of cisplatin and VP-16 (PVP), were examined for frequency of sister chromatid exchange (SCE) and chromosomal aberrations. Three of the 8 patients were treated with the PVP regimen only; however, the others had previously been treated with multiagent chemotherapy consisting of a cyclophosphamide, adriamycin, and vincristine (CAV) regimen or a cyclophosphamide, ACNU and vincristine (CAV') regimen with or without radiotherapy. Significantly increased SCE frequency was observed in previously untreated patients 3 or 4 days after PVP treatment, compared with the pretreatment values. The earlier analysis in the previously treated patients also showed increased SCE frequency, which seemed to return to the normal value as time elapsed after PVP. In addition, abnormal chromosome count distribution and/or increased incidence of structural changes were observed in cultures from all the patients. In general, striking changes in chromosomes were observed in previously treated patients. The aberrations observed in pretreated patients consisted of chromatid gaps and breaks, exchanges, fragments and dicentric chromosomes. In addition to these abnormalities, double minutes like microchromosomes were seen irrespective of radiotherapy. Further studies are needed to elucidate whether any of the chromosomal aberrations observed in this study could participate in the induction of secondary neoplasms.

T-Lymphocyte Colony Formation by Peripheral Lymphocytes of Patients with Non-Hodgkin's Lymphoma

T-Lymphocyte Colony Formation by Peripheral Lymphocytes of Patients with Non-Hodgkin's Lymphoma

Evaluation of adenosine deaminase activity in patients with head and neck cancer

ADA is a key enzyme in the mammalian purine salvage pathway. The lack of ADA activity has been linked to a lack of cellular immunity in various immune and myeloproliferative disorders. Data on its role in patients with solid tumors are scant and inconclusive. In this report, we have evaluated the activity of this enzyme in the peripheral lymphocytes of patients with head and neck squamous cell cancer (HNC). The mean ADA activity in Stage IV patients (0.57 ± 0.08 SEM, n = 12) was significantly lower than that of controls (1.55 ± 0.25 SEM, P < 0.05, n = 14) and also significantly lower that the mean ADA activity in patients with Stages I, II, and III (1.14 ± 0.10 SEM, P < 0.05, n = 17). Fourteen out of 19 controls, Stage I, II, and III patients had positive skin tests compared to 7 out of 10 Stage IV patients. These differences were not statistically significant. There was also no correlation between ADA activity and the absolute lymphocyte counts. Our results indicate that ADA activity in lymphocytes of patients with advanced HNC is lower than that of controls or patients with earlier stages of the disease. ADA may be a more sensitive indicator of suppressed cellular immunity than delayed cutaneous hypersensitivity reactions, or monitoring absolute lymphocyte counts.

Alteration of adenosine deaminase levels in peripheral blood lymphocytes of patients with gastric cancer.

The present study was undertaken to determine the adenosine deaminase (ADA) activity of peripheral lymphocytes in patients with gastric cancer, with respect to the cancer progression, the effect of surgery and/or immunotherapy. The gastric cancer patients showed lower lymphocyte ADA activity than did the normal control. The lymphocyte ADA activity did not decrease with the cancer progression. There was a significant correlation between lymphocyte ADA activity and blastogenesis of lymphocyte by phytohemaglutinin or concanavalin A. Six months following gastrectomy, the lymphocyte ADA activity was increased, as compared with the preoperative value. The ADA activity of patients on post-operative OK-432 showed a greater increase, as compared to that of patients not given this treatment. In conclusion, decreased lymphocyte ADA activity in gastric cancer patients might be due to either the cancer bearing status or to the immunological suppression.