Lymphocyte Ratio In Peripheral Blood Research Articles

Green Synthesis of Gold Nanoparticles from Polygahatous Polysaccharides and Their Anticancer Effect on Hepatic Carcinoma through Immunoregulation.

Hepatic carcinoma is one of the leading causes of morbidity and mortality among all cancers, but no effective treatment measures have been developed. Herein, polystyrene polysaccharide (PSP) extracted from Polygonatum was used to synthesize gold nanoparticles (PSP-AuNPs) by heating and reduction methods, and the characteristics of the PSP-AuNPs were detected after successful synthesis. In vitro, the immunoregulatory effects of PSP-AuNPs were studied by testing the concentrations of NO, TNF-α, and IL-12p70 in the culture media of PSP-AuNPs-treated RAW264.7 macrophages, and the effect of biocompatibility on the viability of RAW264.7 macrophages and L02 cells was studied via a CCK-8 assay. In vivo, tumor-bearing mice were established and treated with PSP-AuNPs, and the anticancer effects were studied by detecting trends in tumor volume, tumor inhibition rate, and tumor cell proliferation index. Immunoregulation was assessed by evaluating the serum levels of TNF-α and IL-10, the CD4+/CD8+ lymphocyte ratio in peripheral blood and the spleen and thymus indices; toxicity was investigated by measuring body weight, liver and renal function indices. The results showed that PSP-AuNPs could regulate immune function both in vitro and in vivo with almost no toxicity. PSP-AuNPs exhibited excellent anticancer effects on hepatic carcinoma in vivo. The anticancer effect could be strengthened, and the toxicity could be reduced by the combined use of PSP-AuNPs and ADM. In conclusion, PSP-AuNPs could be effective as a therapy and adjuvant therapy for treating hepatic carcinoma, providing potential treatment strategies for this disease.

Effects of Koumiss on Intestinal Immune Modulation in Immunosuppressed Rats.

Koumiss is a traditional fermented dairy product with health and medicinal benefits. It is very popular in the Inner Mongolia Autonomous Region of China. The results of relevant studies have shown that koumiss can regulate the gastrointestinal environment, improve the absorption of nutrients, improve the body's intolerance to lactose, enhance the body's immunity, prevent scurvy and atherosclerosis, and aid in the treatment of tuberculosis. However, there are no systematic reports on the effects of koumiss on immunity. In this study, we aimed to decipher the effects of koumiss on intestinal immune modulation. We used liquid chromatography-tandem mass spectrometry (LC-MS) analysis to determine the composition of Koumiss. Using Compound Discoverer software, we compared the mass spectrometry data with the compound information in the online databases ChemSpider and mzCloud to intelligently identify the main chemical components of koumiss. Additionally, we used Mass Frontier small molecule fragmentation libraryTM to determine the structure of fragment ions. A total of 21 components were identified, which clarified the chemical basis of koumiss. These 21 compounds were then used to perform molecular docking with immune-related targets, such as TNF, IL2, IL10, etc. The results indicated good docking activity between most of the compounds and the targets. Then, an immunosuppressive rat model was used to determine the therapeutic effect of koumiss. The results of this study showed that koumiss could, to a certain extent, correct the atrophy of the thymus and spleen in immunosuppressed model rats. The number of leukocytes, lymphocytes, and the CD4+/CD8+ ratio of peripheral blood lymphocytes was also increased. In addition, it could effectively improve the structure of the small intestinal mucosa, which shows that koumiss has a positive effect on the intestinal immune function of immunosuppressed rats. These findings provide an experimental basis for the development and utilization of koumiss as a therapeutic product.

Peptidylarginine Deiminase 4 as a Possible Biomarker of Plaque Instability in Carotid Artery Stenosis

Background and purposeNeutrophil extracellular traps (NETs) exhibit pro-inflammatory and pro-thrombotic properties. However, they have only been reported as important regulators in atherosclerosis, especially in atherothrombosis. We investigated the presence of NETs and plaque instability in patients with carotid artery stenosis. Material and methodsA total of 39 consecutive patients with carotid artery stenosis were evaluated. All patients underwent carotid artery stenting (CAS) with dual protection (simultaneous flow reversal + distal filter) and blood aspiration as a method of distal embolism prevention. Local arterial blood was aspirated at the stent site and peptidylarginine deiminase 4 (PAD4), which is essential for the formation of NETs, was measured. The relationships between PAD4 and the patient profile, blood examination and plaque data were investigated. ResultsThe mean value of PAD4 in local arterial blood in CAS was 0.5 ng/ml. Bivariate analysis demonstrated that PAD4 was associated with the neutrophil to lymphocyte ratio (p = 0.007), high-density lipoprotein (p = 0.02), triglycerides to high-density lipoprotein ratio (p = 0.007), ulceration (p = 0.02) and plaque contrast enhancement on T1 black blood imaging (p = 0.03). In multiple linear regression analyses, PAD4 was correlated with the neutrophil to lymphocyte ratio (p = 0.01) and ulceration (p = 0.01, cut-off value: 0.49 odds ratio: 19.3). ConclusionsPAD4, representative of the presence of NETs, was high in carotid plaques with unstable features. The neutrophil to lymphocyte ratio in peripheral blood was suggested to be a biomarker of vulnerable plaques. Elucidating the role of NETs may aid in clarifying factors that promote the instability of carotid plaques.

Monocyte to Lymphocyte Ratio in Peripheral Blood of Tuberculous Meningitis with HIV Patients in Tertiary Hospital in West Java

Objective : To describe peripheral blood monocyte to lymphocyte (ML) ratio in tuberculous meningitis (TBM) patients with human immunodeficiency virus (HIV) infection in Dr. Hasan Sadikin General Hospital Bandung as a tertiary hospital in West Java Province, Indonesia. Method: A cross-sectional study with retrospective data approach was done in Dr. Hasan Sadikin General Hospital, Bandung. Data were collected from TBM patients who were hospitalized in Dr. Hasan Sadikin General Hospital, Bandung in the period of 2014–2016. The sample size was determined using total sampling method. General data, clinical manifestation data, and laboratory finding data were collected. The ML ratio was collected and presented into three groups of percentile (25th, 25–75th and 75th) based on the pre-defined cut-off. Result : Six subjects (40%) had an ML ratio of ≤0.47 and 3 subjects had an ML ratio of ≥1.22 in TBM with HIV population. Among TBM with HIV-negative population, there were 16 subjects had ML ratio ≤0.47, and 19 subjects had ML ratio ≥1.22. Conclusion : The ML ratio in TBM with HIV infection has become additional tool for detecting the development of TBM with HIV-infected, as well as TBM with non-HIV-infected. Therefore, it could help directing the patients with clinical suspicious of TBM into the diagnosis algorithm and treatment of TBM, to have better outcome. Keywords: Human immunodeficiency virus infection , lymphocyte, monocyte, monocyte to lymphocyte ratio, tuberculous meningitis DOI: 10.15850/ijihs.v6n1.1140

Platelet to lymphocyte ratio in peripheral blood and body mass index: novel independent prognostic factors in patients with melanoma

Objective: To investigate whether platelet to lymphocyte ratio (PLR) in peripheral blood and body mass index (BMI) can be independent prognostic factors in patients with melanoma. Methods: Clinical date of 140 patients with melanoma in the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital from January 1, 2010 to December 31, 2015 were analyzed retrospectively.Receiver operating characteristic (ROC) curve was performed the optimal cut-off value for PLR.The 140 patients were divided into high PLR group and low PLR group.According to "Guidelines for prevention and control of overweight and obesity in Chinese adults" , the patients were divided into high BMI group and low BMI group.The relationship between PLR, BMI with overall survival (OS), progression free survival (PFS) and disease free survival (DFS) were analyzed.The Kaplan-Meier method and Log rank test was used for univariate survival analysis and Cox proportional hazards regression model for multivariate analysis. Results: The optimal cut-off value of PLR determined by ROC curve was PLR=120.15, and BMI threshold was 24.Univariate survival analysis showed that PLR, BMI and clinical stage were the factors affecting the OS in patients (P<0.05). The median survival time (MST) was 21 months in the whole group and 17 months in the high PLR group, 34 months in the low PLR group, respectively; the MST in the high and low BMI group were 29 months and 13 months, respectively.The difference was statistically significant (P<0.05). The effects of PLR and BMI on PFS and DFS were not statistically significant.Cox multivariate analysis showed that PLR, BMI and clinical stage were independent prognostic factors of OS (P<0.05). And BMI was the only independent protective factor for OS, the risk of death decreased by 0.611 times, with each unit increased for BMI.Clinical subgroup analysis showed that PLR also was risk factor to the prognosis of patients with stage Ⅱ, Ⅲ, and Ⅳ (P<0.05). Conclusions: PLR is an independent prognostic risk factor for patients with melanoma, and BMI is an independent protective factor.PLR and BMI are important factors in prognostic evaluation of melanoma.

Neutrophil to lymphocyte ratio in peripheral blood: a novel independent prognostic factor in patients with head and neck squamous cell carcinoma

Objective: To investigate whether neutrophil to lymphocyte ratio (NLR) in peripheral blood can be an independent prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Clinical data of 97 HNSCC patients who received surgical treatment in our department between January 2008 and January 2012 were analyzed retrospectively. The 97 patients were divided into low NLR group (NLR≤5, n=69) and high NLR group (NLR>5, n=28) according to the NLR in preoperative peripheral blood. The relationships of NLR and clinicopathological features were analyzed. Kaplan-Meier method was used for univariate survival analysis and Cox proportional hazard model for multivariate survival analysis. Results: The clinical stages were significantly different between high NLR group and low NLR group (P<0.05), however, the age, gender, location, lymph node metastasis, smoking and alcohol of the two groups showed no significant differences (P> 0.05 of all). Univariate survival analysis showed that smoking, lymph node metastasis, clinical stage and NLR value were risk factors for 3-year overall survival (OS) rate and relapse-free survival (RFS) rate of HNSCC patients (P<0.05). The OS rate of high NLR and low NLR groups was 42.9% and 91.3%, and the RFS rate was 44.2% and 80.1%, respectively, with a statistically significant difference (P<0.05 for both). Cox multivariate survival analysis showed that clinical stage and NLR were independent factors for prognostic evaluation of HNSCC patients (P<0.05 for both). Conclusions: NLR level is significantly associated with clinical stage of HNSCC. High NLR is an independent prognostic rick factor and plays an important role in prognostic evaluation of HNSCC patients.

Regulation of Nutritional Metabolism in Transition Dairy Cows: Energy Homeostasis and Health in Response to Post-Ruminal Choline and Methionine.

This study investigated the effects of rumen-protected methionine (RPM) and rumen-protected choline (RPC) on energy balance, postpartum lactation performance, antioxidant capacity and immune response in transition dairy cows. Forty-eight multiparous transition cows were matched and divided into four groups: control, 15 g/d RPC, 15 g/d RPM or 15 g/d RPC + 15 g/d RPM. Diet samples were collected daily before feeding, and blood samples were collected weekly from the jugular vein before morning feeding from 21 days prepartum to 21 days postpartum. Postpartum dry matter intake (DMI) was increased by both additives (P < 0.05), and energy balance values in supplemented cows were improved after parturition (P < 0.05). Both RPC and RPM decreased the plasma concentrations of non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (P < 0.05), but increased the plasma levels of glucose, very-low-density lipoprotein (VLDL) and apolipoprotein B100 (ApoB 100, P < 0.05). The supplements improved milk production (P < 0.05), and increased (P < 0.05) or tended to increase (0.05 < P < 0.10) the contents of milk fat and protein. The post-ruminal choline and methionine elevated the blood antioxidant status, as indicated by total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) activity and the vitamin E concentration (P < 0.05), and reduced the plasma malondialdehyde (MDA) level (P < 0.05). Furthermore, RPM and RPC elevated the plasma interleukin 2 (IL-2) concentration and the CD4+/CD8+ T lymphocyte ratio in peripheral blood (P < 0.05). Alternatively, the levels of tumor necrosis factor-α (TNF-α) and IL-6 were decreased by RPM and RPC (P < 0.05). Overall, the regulatory responses of RPC and RPM were highly correlated with time and were more effective in the postpartum cows. The results demonstrated that dietary supplementation with RPC and RPM promoted energy balance by increasing postpartal DMI and regulating hepatic lipid metabolism, improved postpartum lactation performance and enhanced antioxidant capacity and immune function of transition dairy cows.

P.6.d.020 Dose-dependent effects of repeated intravenous cocaine on CD4:CD8 lymphocyte ratio in peripheral blood of rats

P.6.d.020 Dose-dependent effects of repeated intravenous cocaine on CD4:CD8 lymphocyte ratio in peripheral blood of rats

Cocaine administration increases CD4/CD8 lymphocyte ratio in peripheral blood despite lymphopenia and elevated corticosterone

The CD4/CD8 lymphocyte ratio in peripheral blood is used in the diagnosis of HIV infection, autoimmune disorders or susceptibility to infections. The present experiment aimed to evaluate the lymphocyte subsets, their distribution and CD4/CD8 ratio in blood after repeated, intravenous administration of cocaine. Adult male Wistar rats received three daily, in 30 min intervals, intravenous infusions of cocaine hydrochloride (5 mg/kg) or saline for 14 consecutive days. After each infusion the locomotor-activating effects of cocaine were assessed. Blood samples were collected 30 min after the last daily infusion on the 1st, 7th and 14th day of treatment. Total leukocyte numbers, percentages of leukocyte subpopulations, and T, B, NK, T CD4 +, and T CD8 + lymphocyte subsets, IFN-γ, and plasma corticosterone were determined. Repeated cocaine treatment resulted in an increase in neutrophil numbers and a significant decrease in total leukocyte and lymphocyte numbers involving a significant reduction in numbers of T, B, and NK lymphocyte subsets. T CD4 + and T CD8 + lymphocyte numbers were reduced but with a considerably smaller decrease in T CD4 + number. Cocaine treatment altered proportions between the lymphocyte subsets by decreasing the percentages of T CD8 +, B, and NK cells but increasing a percentage of T CD4 + cells. Destabilization in proportions between T CD4 + and T CD8 + was manifested as an elevated CD4 /CD8 ratio that occurred despite increased plasma corticosterone and the lymphocytopenia. Cocaine did not affect the concentration of IFN-γ. The results suggest that although cocaine induced lymphopenia, it did not suppress the overall immune activity in terms of the CD4 /CD8 ratio.

The Effects of Age and Gender on Gingival Tissue and Peripheral Blood T-Lymphocyte Subsets: A Study in Mice

The aim of this study is to investigate the effects of age and gender on relative number of CD4+ and CD8+ T lymphocyte and CD4+/CD8+ ratios in gingival tissue and peripheral blood of periodontally healthy BALB/c mice with flow cytometric analysis. The study was carried out on periodontally healthy 60 BALB/c mice. They were separated into five groups according to the life expectancy: Group I (newborn, 1–10 days old), Group II (age at weaning, 21–28 days old), Group III (age of sexual maturity, puberty, 7–8 weeks old), Group IV (adult, 8 months old), and Group V (the aged, 14 and over). Males and females were equally represented in each group. CD4+ and CD8+ T lymphocytes and CD4+/CD8+ ratio values in gingival tissue and peripheral blood were determined using flow cytometry in the biopsy samples. The relative number of CD8+ T lymphocyte in gingival tissue was higher in puberty (p < 0.05) and the aged (p < 0.05), with more significantly difference in males (p < 0.05). The CD4+/CD8+ ratios in gingival tissue were lower in puberty group and the-aged groups compared to the other groups (p < 0.05).The peripheral blood CD4+/CD8+ ratio increased in puberty and the aged groups. These differences were more significant in females than in males (p < 0.05). There were considerable negative correlations between CD4+/CD8+ T lymphocyte ratio in gingival tissue and CD4+/CD8+ T lymphocyte ratio in peripheral blood in puberty (r = 0.647, p < 0.01) and the aged ( r = 0.599, p < 0.05). In conclusion, our data suggest that CD4+/CD8+ T lymphocyte ratios in peripheral blood increase periodontally healthy mice in puberty and the old groups, while CD4+/CD8+ T lymphocyte ratios in gingival tissue decrease in the same groups. The relative number of CD8+ T lymphocytes increases in gingival tissue in puberty and the old groups when it decreases in peripheral blood. Results from this study indicated that periodontally healthy BALB/c mice may represent important information to determine the character of an immune response in the course of a lifetime.

CD45RA+ ICAM-3+ lymphocytes in interferon-beta1b-treated and -untreated patients with relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is believed to be an autoimmune disease of the human central nervous system mediated by autoreactive T cells. Interferon-beta1b (IFN-beta1b) has been shown to be effective in reducing disease activity defined by clinical and magnetic resonance imaging (MRI) criteria in relapsing-remitting MS (RRMS). Yet, the exact mechanisms by which these benefits are achieved remain unknown. CD45RA is a marker for naive T lymphocytes and intercellular adhesion molecule-3 (ICAM-3) is expressed on resting lymphocytes. Forty-eight patients with RRMS, 24 of them treated with recombinant IFN-beta1b and 24 untreated, were enrolled in this prospective study over 18 months. We investigated the percentage of CD45RA+ ICAM-3+ cells within the total lymphocyte subset in the peripheral blood serially every 3 months and in CSF once at baseline. Detailed clinical examination including Expanded Disability Status Scale (EDSS) score was performed every 3 months and cranial MRI scans were assessed every 6 months. We found a temporary increase in the CD45RA+ ICAM-3+ lymphocyte ratio in peripheral blood of both untreated and IFN-beta1b-treated RRMS patients. Moreover, we determined a significant negative correlation (r = -0.5874; P < 0.01) between age as well as the EDSS score (r = -0.3629; P < 0.05) and the percentages of CD45RA+ ICAM-3+ lymphocytes in peripheral blood but a positive correlation between EDSS score and the CD45RA+ ICAM-3+ ratio (r = 0.3913; P < 0.05) in the CSF at baseline. CD45RA+ ICAM-3+ lymphocyte ratio in peripheral blood might indicate immunosenescence in MS. However, from our data it cannot be finally concluded whether it is also influenced by IFN-beta1b treatment.

Modulation of lymphocyte and monocyte activity after intravenous immunoglobulin administration in vivo

In 12 patients with primary hypogammaglobulinaemia we investigated the in vivo effect of one bolus injection (400 mg/kg) of intravenous immunoglobulin (IVIG) on lymphocyte subsets and monocytes in peripheral blood, on plasma levels of soluble factors reflecting monocyte and lymphocyte activity and on lymphocyte proliferation and generation of reactive oxygen species (ROS) from monocytes analysed in vitro. Several immunological changes were induced by IVIG infusion. First, there was a significant decrease in CD4+/CD8+ lymphocyte ratio in peripheral blood, reflecting a significant increase in circulating numbers of CD8+ lymphocytes. Second, although there was no significant change in plasma levels of soluble CD8 antigen, there was a significant decrease in soluble CD8 antigen/CD8+ lymphocyte ratio, suggesting a down-regulation of CD8+ lymphocyte activity. Third, there was a significant increase in plasma levels of neopterin, suggesting in vivo activation of monocytes/macrophages. Fourth, the was a down-modulation of mitogen-stimulated lymphocyte proliferation in vitro, and this down-regulation was significantly correlated with the increase in plasma neopterin levels. Finally, there was a significant decrease in zymosan-stimulated, but not in phorbol myristate acetate-stimulated, ROS generation from monocytes as evaluated by nitroblue tetrazolium reduction. The ability of IVIG administration in vivo to down-modulate lymphocyte proliferation and ROS generation from monocytes in patients with persistent immune activation may be relevant for the clinical effects of IVIG in a variety of immune-mediated disorders.

Intravenous immunoglobulin treatment in women with recurrent abortions: increased cytokine levels and reduced Th1/Th2 lymphocyte ratio in peripheral blood.

The aim of this study was to investigate changes in peripheral blood Th1/Th2 cytokine levels and lymphocyte ratios after massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology. Serum Th1 (IFN-gamma, TNF-alpha) and Th2 cytokine (IL-4, IL-10) levels were assessed by ELISA methods (n = 9) and peripheral blood Th1/Th2 lymphocyte ratios (n = 4) by flow cytometry before and after MIVIg treatments in women with four or more consecutive RSA. Pre-treatment serum IFN-gamma (0.06 +/- 0.09 pg/mL, mean +/- SD), TNF-alpha (0.21 +/- 0.45 pg/mL), IL-4 (0.70 +/- 1.16 pg/mL), and IL-10 (1.12 +/- 1.67 pg/mL) increased to 0.17 +/- 0.16 pg/mL, 0.77 +/- 0.28 pg/mL, 1.82 +/- 0.89 pg/mL, and 3.44 +/- 0.48 pg/mL, respectively, after MIVIg treatments (P < 0.05). CD4-positive IFN-gamma/IL-4 lymphocyte ratios (17.3 +/- 9.1) were reduced to 11.5 +/- 7.1 after treatment (P < 0.05). Massive intravenous immunoglobulin treatments increased peripheral blood cytokine levels and decreased Th1/Th2 lymphocyte ratios; thus, MIVIg treatments modify the peripheral Th1/Th2 balance.

Immunological analysis of the rats with anterior hypothalamic lesions

We have previously identified the suppression of lymphocyte blastogenesis and the acceleration of growth of subcutaneous tumors by bilateral anterior hypothalamic lesions in rats. The present study was performed to clarify the changes in lymphocyte subsets and natural killer (NK) activity after making the lesions. The influence on immunological memory was also studied. The CD4/CD8 ratio of peripheral blood lymphocytes and spleen cells, T cell receptor αβ-positive cells of the thymocytes and NK activity of the spleen cells decreased significantly. Major histocompatibility complex (MHC) antigen expression on RBL-1 cells injected intraperitoneally into pre-immunized rats was also suppressed. These results suggest that the anterior hypothalamus has some influences on the control of the cellular immunological functions at the peripheral level, on the maturation of T cells at the level of thymus and on the antigen recognition by T cell receptors and MHC antigens.

Parotid gland enlargement and xerostomia associated with labial sialadenitis in HIV-infected patients

Infection with human immunodeficiency virus (HIV) may be associated with enlargement of the major salivary glands or symptoms of dry mouth. We term this condition HIV-associated salivary gland disease (HIV-SGD). In this report we describe 12 patients with HIV-SGD. Nine patients (one child, eight adults) had enlargement of the parotid glands, and three had xerostomia alone. Symptoms of dry mouth, dry eyes or arthralgia occurred in 11, five and five patients, respectively. Salivary flow rates were normal or slightly reduced in seven patients and severely.reduced in five. Labial salivary gland (LSG) biopsy specimens from patients contained lymphocytic ilfiltrates in focal and other patterns, whereas specimens from three HIV-infected patients without salivary gland symptoms did not. The inflammatory infiltrates in LSG specimens showed a preponderance of T8-positive cells and a tissue T4/T8 average ratio of 0.66. The mean T4/T8 ratio of peripheral blood lymphocytes was 0.4. Serum antinuclear antibodies were present in one patient, but rheumatoid factor, SS-A, and SS-B antibodies were absent in all. Search for Epstein-Barr virus and cytomegalovirus in the LSG tissue of the six patients tested did not reveal evidence of antigens or DNA. HIV-SGD patients show a number of similarities to and differences from patients with Sjögren's syndrome (SS). The similarities include the oral and salivary features, histopathology and possibly changes in other organs. The differences include the lower salivary gland T4/T8 ratio and the absence of autoantibodies in serum. The causes of HIV-SGD as well as of Sjögren's syndrome are unknown.

Abnormalities in CD4+ T-lymphocyte subsets in inflammatory rheumatic diseases

The monoclonal antibodies anti-2H4 and anti-4B4 identify the suppressor-inducer (CD4+2H4+) and helper-inducer (CD4+4B4+) subpopulations of CD4 (T4+) lymphocytes, respectively. The cell surface phenotype of peripheral blood lymphocytes and synovial fluid lymphocytes in patients with rheumatoid arthritis and other inflammatory joint diseases was analyzed by use of these and other well-characterized anti-T-cell monoclonal antibodies. In the synovial fluid of patients with rheumatoid arthritis, there was a markedly decreased percentage of T4+2H4+ suppressor-inducer cells (3.1 ± 1 percent) and an increased percentage of T4+4B4+ helper-inducer cells (29.1 ± 9 percent) as compared with the proportions found in the peripheral blood of normal individuals (T4+2H4+: 19.0 ± 6 percent, T4+4B4+: 23.0 ± 7 percent). Moreover, patients with other chronic and acute inflammatory joint diseases exhibited highly similar synovial T-cell findings to those of the patients with rheumatoid arthritis (T4+2H4+: 4.2 ± 3 percent, T4+4B4+: 33.1 ± 9 percent). In contrast, there were no significant differences between the normal control subjects and patients with rheumatoid arthritis in the percentage of T4+2H4+ cells in peripheral blood lymphocytes, nor were there significant differences between normal control subjects, patients with rheumatoid arthritis, and patients with other joint diseases (osteoarthritis, gout, B27+ spondyloarthropathy, and psoriatic arthritis) in the number of T4+4B4+ cells or in the T4/T8 ratio of peripheral blood lymphocytes. However, very low numbers of T4+2H4+ (suppressor-inducer) peripheral blood lymphocytes were seen in a subgroup of patients, including five of seven with Reiter's syndrome and several patients with systemic rheumatic disease syndromes. In addition, although the percentage of T4+2H4+ cells in peripheral blood lymphocytes of patients with osteoarthritis (13.7 ± 7 percent) and gout (14.3 ± 7 percent) was decreased compared with that of normal controls (19.0 ± 6 percent) (osteoarthritis versus normal controls p <0.025), this difference appeared to reflect alterations due to age rather than disease. Consistent with the phenotypic changes observed, synovial T cells were also functionally defective, since autologous mixed lymphocyte reaction-activated T4 cells from the synovial fluid of patients with rheumatoid arthritis failed to exhibit suppressor-inducer activity. The results indicate that diminished proportions of CD4+2H4+ (suppressor-inducer) cells and increased proportions of CD4+4B4+ (helper) cells are a common feature of CD4+ cells in synovial fluid in rheumatoid arthritis as well as a variety of other inflammatory disorders, whereas modest changes in CD4+2H4+ peripheral blood lymphocytes are seen in older individuals and more marked decreases are observed only in a more selected group of patients. These changes may be of potential functional importance in the regulation of the immune response in a variety of clinical settings.

Clinical, Gross, and Histological Findings in Herring Gulls and Atlantic Puffins that Ingested Prudhoe Bay Crude Oil

Oral doses of 0, 1, 4, 5, 10, or 20 ml of Prudhoe Bay crude oil/kg body weight/day were given to herring gull and Atlantic puffin nestlings for 5 to 7 consecutive days. Gulls defecated substantial amounts of oil within 10 to 15 minutes after receiving a dose. Clinical signs and lesions occurred only in birds given greater than or equal to 10 ml oil/kg body weight/day. Gulls consumed less food and lost weight. Two categories of lesions were observed: those considered secondary to a primary toxic hemolytic disease, and those considered nonspecific reactions to stress. The former included phagocytosis of degenerate erythrocytes in the liver and spleen, hemoglobin resorption droplets in renal proximal tubule cells, and erythroid hyperplasia in the bone marrow; the latter included lymphocyte depletion in primary lymphoid tissues, an increase in heterophil: lymphocyte ratio in peripheral blood, lipid depletion and necrosis in adrenal steroidogenic cells, and an increased prevalence and severity of lesions in the bursa of Fabricius. These findings indicated that the primary target of oil toxicity was the peripheral red blood cell, but that significant stress-related lesions were also associated with ingestion of oil.

Studies of lymph nodes from patients with classical hemophilia

Within the last 18 months, we have noted the development of unexplained lymph node enlargement in otherwise asymptomatic patients with hemophilia. Because such changes are poorly understood and, in some patient groups, may be related to the acquired immunodeficiency syndrome (AIDS), we studied the enlarged lymph nodes in four patients with severe factor VIII deficiency and abnormally low peripheral blood helper-inducer/suppressor cell (OKT4/OKT8) ratios. Surgically excised lymph nodes were studied for histopathologic, electron microscopic, and chromosomal changes. Cell suspensions from these and normal nodes were also studied using monoclonal antibodies. Excised lymph nodes showed follicular hyperplasia. Electron microscopy revealed no viral particles or vesicular rosettes. Chromosomal aberrations included an acrocentric marker chromosome in one patient and monosomy 21 in another. T lymphocyte ratios (OKT4/OKT8) in lymph node suspensions were lower than those in nodes from normal controls (1.2 v 6.1) and reflected the lymphocyte ratio in peripheral blood. Mature B cell percentages were increased in the lymph nodes from patients with hemophilia (38% v 27% in controls). Patients treated with factor VIII concentrates and male homosexuals have similarities in persistent lymph node enlargement, histologic features of follicular hyperplasia, and changes in lymph node and circulating lymphocyte subpopulations.

Studies of Lymph Nodes From Patients With Classical Hemophilia

Abstract Within the last 18 months, we have noted the development of unexplained lymph node enlargement in otherwise asymptomatic patients with hemophilia. Because such changes are poorly understood and, in some patient groups, may be related to the acquired immunodeficiency syndrome (AIDS), we studied the enlarged lymph nodes in four patients with severe factor VIII deficiency and abnormally low peripheral blood helper-inducer/suppressor cell (OKT4/OKT8) ratios. Surgically excised lymph nodes were studied for histopathologic, electron microscopic, and chromosomal changes. Cell suspensions from these and normal nodes were also studied using monoclonal antibodies. Excised lymph nodes showed follicular hyperplasia. Electron microscopy revealed no viral particles or vesicular rosettes. Chromosomal aberrations included an acrocentric marker chromosome in one patient and monosomy 21 in another. T lymphocyte ratios (OKT4/OKT8) in lymph node suspensions were lower than those in nodes from normal controls (1.2 v 6.1) and reflected the lymphocyte ratio in peripheral blood. Mature B cell percentages were increased in the lymph nodes from patients with hemophilia (38% v 27% in controls). Patients treated with factor VIII concentrates and male homosexuals have similarities in persistent lymph node enlargement, histologic features of follicular hyperplasia, and changes in lymph node and circulating lymphocyte subpopulations.

Effect of aclacinomycin A on bone marrow (author's transl)

Japan White rabbits were treated with aclacinomycin A, a new anthracycline antitumor antibiotic, at a dose of 6.25 or 25.0 mg/kg by single intravenous, or 12.5 or 50.0 mg/kg by single oral administration, respectively. Beagle dogs were treated at a dose of 3.0 or 6.0 mg/kg by single intravenous injection. In rabbits in higher dose groups, RBC and WBC counts as well as lymphocyte ratio in peripheral blood decreased on day 1. Nucleated cell counts and erythroid elements in bone marrow decreased to raise M/E ratio (Myeloid/Erythroid ratio) on day 3. In a dog given at 6.0 mg/kg, WBC and platelet counts, lymphocyte and neutrocyte per cents in peripheral blood and also nucleated cells, particularly erythroid elements in bone marrow remarkably decreased on day 3 accompanied with an increase in M/E ratio. These changes were almost completely recovered by day 14 in both animals. No abnormalities were found in lower dose groups. Male Wistar rats, treated with the drug at a dose of 1.5 mg/kg by daily intraperitoneal injection for 30 days, showed slight decreases in peripheral WBC and RBC counts and M/E ratio in bone marrow. No change was observed in rats treated at 0.75 mg/kg and less for 30 days.