Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells

Neuropsychological profiles were assessed in a large group of nondemented control subjects (n = 261) and individuals with dementia of the Alzheimer type (DAT) (n = 407) by subjecting their psychometric test results to a factor analysis. Nondemented control subjects were functionally homogeneous with only one factor accounting for the results. The results of the factor analysis on the very mild DAT and mild DAT groups, however, yielded a mental control/frontal factor, a memory-verbal/temporal factor, and a visuospatial/parietal factor. Forty-one of the original set of participants came to autopsy an average of 5.1 years after psychometric testing and had neurofibrillary tangles, total senile plaques, and cored senile plaques estimated from frontal, temporal, and parietal regions. The results of correlations indicated that the relative burden of cored senile plaques was systematically related to the three psychometric factors. These results suggest a connection between the specific functions as defined by neuropsychological measures and specific neuropathology occurring in associated areas of cortex.     

Cyclin D1 overexpression in malignant lymphomas

Cyclin D1, the regulatory subunit of certain protein kinases thought to advance the G1 phase of the cell cycle, is now established as a proto-oncogene, with evidence indicating that its derangement may contribute to the uncontrolled cell growth characteristic of tumors. The chromosomal translocation t(11;14)(q13:q32), involving rearrangement of the BCL-1 locus, is closely associated with human lymphoid neoplasia affecting mantle cell lymphomas (MCL). Recently, the putative BCL-1 proto-oncogene turned out to be none other than the cyclin D1 gene. Although the observed break points in the BCL-1 locus are not tightly clustered, its rearrangement has been documented in 40-70% of cases of mantle cell lymphoma, whereas it only rarely occurs in other B cell lymphomas. Of note, all of the known break points leave the cyclin D1 coding region structurally intact and result in increased protein expression, implying that this may provide a highly sensitive and specific marker for MCL. Recent studies demonstrated that immunohistochemical detection in paraffin-embedded material, using a monoclonal antibody, is very useful for routine diagnosis. Current knowledge of cyclin D1 overexpression in malignant lymphomas, with emphasis on its clinicopathologic significance, is reviewed.     

Correlations between apoptotic and proliferative indices in malignant non-Hodgkin's lymphomas

Cell production versus cell loss rates were estimated, across the boundaries of histological classification, in 50 cases of malignant non-Hodgkin's lymphomas by use of mitotic indices, percentage of Ki-67+ cells and percentage of PC10+ cells as proliferative indices, and the relative number of apoptotic bodies (apoptotic indices, AIs) as parameters. Regression analysis revealed significant (P < 0.01) positive correlations between the AIs and the proliferative indices; among the immunohistochemically assessed proliferative indices; and between these, the mitotic indices and the AIs on the one hand and histological malignancy grades on the other hand. The cellular protein BCL-2, which counteracts apoptosis, was significantly (P < 0.01) more often expressed in lymphomas with low than in those with high AIs. Multivariate analysis of data showed that of all parameters tested in this series, only the AIs correlated significantly (P < 0.05) with overall lethality. The correlation between BCL-2 positivity of lymphoma cells and overall survival did not quite attain significance (P = 0.08). Results of the present study suggest that high AIs and lack of BCL-2 expression may be adverse prognostic factors, independent of histological grade.     

Serial liver and spleen scanning in patients with malignant lymphomas

Blood samples from 580 African leprosy patients living in Rhodesia have been phenotyped for the plasma cholinesterase variants. The Africans have been grouped according to country of origin and tribal affiliation. We have found no individual with an Ea1 gene and are unable to resolve the contradictory evidence for an association between this gene and leprosy. The frequency of the Ef1 gene is higher than that usually found in Caucasian populations, being 0.046 in lepromatous leprosy patients and similar to the 0.056 found in healthy African controls. In tuberculoid leprosy patients the frequency is, however, significantly lower at 0.019. On the other hand, the frequency of the C5+ variant is essentially the same for the tuberculoid leprosy patients and the healthy controls (4%) while for the lepromatous leprosy patients it is about 7% approaching the 10-15% found in many Caucasian populations.     

Diagnostic and prognostic value of interleukin-6 in malignant non-Hodgkin's lymphomas

Sixty six patients with non-Hodgkin's lymphomas (NHL) were studied, interleukin-6 (IL-6) was revealed in the blood sera of 33 patients. IL-6 was revealed more frequently in patients with high-grade malignant (p < 0.05) than in those with low-grade malignancy. The largest group of IL-6 positive patients included NHL patients with diffuse large B-cell lymphoma and angioimmunoblastic lymphoma. The marked relationship was found between the serum IL-6 levels and the stage of disease: the serum IL-6 level was significantly lower in untreated patients with Stages II and III disease than in those with end-stage (IV) NHL. IL-6 significantly decreased upon remission, comparable with its level before the initiation of treatment. Analysing the association of prognosis of disease with the serum IL-6 showed that in the group of patients with good (The SNLG index < 2) and intermediate (2 < SNLG index < by 2.6) prognosis, the concentration of this cytokine was significantly lower than in those with poor prognosis (SNLG index > 2.6). There was a significant decrease of the total survival rates of NHL with serum IL-6 found. Therefore, IL-6 is a good prognostic marker in NHL and associated with the activity of a malignant process. Additionally, the increased serum IL-6 levels correlated with NK activities positively and with serum IL-4 levels negatively.     

Expression of fibrogenic cytokines in desmoplastic malignant melanoma

OBJECTIVE: Research has confirmed substantial links between OCD and AN. Not only are there psychopathological similarities between the two syndromes, but a marked neurochemical correspondence. Extensive exercising is a common feature of AN and also has relevance in its links with OCD. There is evidence from the exercise-induced weight-loss syndrome in animals that exercise and caloric restriction, in combination, tend to increase serotonergic activity in a synergistic manner. This syndrome has been proposed as a valid model of OCD as well as for AN. To date, little research has directly tested this theory in the human condition. METHOD: Fifty-three AN patients were categorized as high-level exercisers (N = 22) or moderate/nonexercisers (N = 31) based on the frequency of their physical activity over the year before assessment. RESULTS: Exercisers scored significantly higher on a measure of OC personality characteristics, OC symptomatology, and perfectionism--a personality factor associated with the development of Obsessive-Compulsive Personality Disorder. On the other hand, there were no group differences on other salient eating disorder characteristics such as body esteem, self-esteem, or weight preoccupation. There were also no differences in degree of emaciation as indicated by Body Mass Index. CONCLUSIONS: Findings suggest that among AN patients obsessional personality characteristics are linked to high-level exercising, and that exercising is associated with a greater degree of OC symptomatology. Results are discussed in the context of current theories of AN, OCD, and some biological mechanisms.     

Proliferation and apoptosis in malignant and normal cells in B-cell non-Hodgkin's lymphomas

We have examined apoptosis and proliferation in lymph node cell suspensions from patients with B-cell non-Hodgkin's lymphoma using flow cytometry. A method was developed which allowed estimation of the fractions of apoptotic cells and cells in the S-phase of the cell cycle simultaneously with tumour-characteristic light chain expression. Analysis of the tumour S-phase fraction and the tumour apoptotic fraction in lymph node cell suspensions from 95 B-cell non-Hodgkin's lymphoma (NHL) patients revealed a non-normal distribution for both parameters. The median fraction of apoptotic tumour cells was 1.1% (25 percentiles 0.5%, 2.7%). In the same samples, the median fraction of apoptotic normal cells was higher than for the tumour cells (1.9%; 25 percentiles 0.7%, 4.0%; P = 0.03). The median fraction of tumour cells in S-phase was 1.4% (25 percentiles 0.8%, 4.8%), the median fraction of normal cells in S-phase was significantly lower than for the tumour cells (1.0%; 25 percentiles 0.6%, 1.9%; P = 0.004). When the number of cases was plotted against the logarithm of the S-phase fraction of the tumour cells, a distribution with two Gaussian peaks was needed to fit the data. One peak was centred around an S-phase fraction of 0.9%; the other was centred around 7%. These peaks were separated by a valley at approximately 3%, indicating that the S-phase fraction in NHL can be classified as 'low' (< 3%) or 'high' (> 3%), independent of the median S-phase fraction. The apoptotic fractions were log-normally distributed. The median apoptotic fraction was higher (1.5%) in the 'high' S-phase group than in the 'low' S-phase group (0.8%; P = 0.02). However, there was no significant correlation between the two parameters (P > 0.05).     

Clinical considerations on primary malignant lymphomas of the stomach

Starting from a critical revision of eight cases of primitive malignant gastric lymphoma that they had observed during the last four years in Surgical Clinic of University of Pavia, the AA. refer the notions in regard to this neoplastic form. After having discussed the problems of etiopathogenesis of lymphoma and the most characteristic clinical forms, the AA. describe the modern views of diagnosis and the therapy on the base of literature and their personal casistry. Outlined the necessity of a precocious diagnosis and the possibilities that gastroscopy with looked at biopsy affers, the AA., also on the base of their experience, show like selective therapy of primitive malignant gastric lymphoma, the surgical treatment with complememtary cyclic polichemioterapy.     

恶性淋巴瘤患者凝血纤溶指标变化的意义

目的 探讨恶性淋巴瘤患者凝血纤溶指标的变化,提高对恶性淋巴瘤患者合并血栓的认识方法应用全自动血凝分析仪对20名健康对照及71例恶性淋巴瘤患者的血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原定量(FIB)及凝血酶时间(TT)进行检测,用免疫散射比浊法测定两组血浆D-二聚体(D-DI)的含量.结果 71例恶性淋巴瘤患者APTT(30.44±1.43)s、FIB(3.28±0.20)g/L、D-DI(297.05±56.59)μg/L均高于健康对照组的(23.72±0.76)s、(2.57±0.22)g/L、(94.50±26.07)μg/L,差异有统计学意义(P＜0.05).Ⅰ、Ⅱ期淋巴瘤患者各项凝血纤溶指标较健康对照组差异无统计学意义(P＞0.05).Ⅲ、Ⅳ期淋巴瘤患者APTT延长,FIB增高,与健康对照组及Ⅰ、Ⅱ期组比较差异有统计学意义(P＜0.05).合并静脉血栓患者7例,该组与Ⅰ、Ⅱ期患者相比FIB及D-DI均高,与Ⅲ、Ⅳ期患者相比D-DI明显升高.结论 恶性淋巴瘤患者存在凝血纤溶指标的异常,需定期动态检测,化疗后易发生静脉血栓,需及早预防,延长患者生存期.     

Vasopressin : a potent autocrine/paracrine regulator of mammal adrenal functions

The control of adrenal functions by locally secreted neuropeptides or neurotransmitters is of great physiological importance. Vasopressin (VP) is one of these autocrine/paracrine regulators. We demonstrated by RT-PCR and perifusion experiments that rat and human adrenal medulla expressed and released vasopressin under basal conditions and under stimulation by acetylcholine. Intra-adrenal concentrations of VP may be sufficient to activate adrenal VP receptors. In the cortex, only the V1a receptor subtype has been detected. It triggered both steroid secretion and cortical growth. In the medulla, both V1a and V1b receptor subtypes were expressed. V1b receptors were mainly present on chromaffin cells and stimulated catecholamine secretion. The role of the V1a receptor remains unclear. Pathophysiological studies also revealed that human pheochromocytoma did not overexpress vasopressin receptors but might oversecrete vasopressin causing high plasma VP concentrations and elevated blood pressure.     

Burkitt-type lymphoma in France among non-Hodgkin malignant lymphomas in Caucasian children

In a retrospective analysis of 87 cases of Caucasian childhood non-Hodgkin malignant lymphoma (NHML) from Lyon, France, all the case were diffuse lymphomas, but 47 were diagnosed as monomorphic small non-cleaved NHML, pathologically indistinguishable from Burkitt's lymphoma (BL). BL could then be the most frequent childhood lymphoma in France. This homogeneous series allows better definition of the characteristics of BL within NHML. Age distribution is similar to that of endemic BL, with a sex ratio of 3.7/1. Abdominal masses are initially present in 68% of the cases, whereas jaw is involved in only 4%. The disease is characterized by its overwhelming evolution in the absence of therapy. However, complete remission (CR) is usually obtained after the first chemtherapy regimen. Most relapses occur at 3-8 months. Death could be related to cerebrospinal fluid (CSF) involvement, local recurrence or secondary marrow involvement. Ninety per cent of the patients alive with no evidence of disease (NED) 8 months after CR can be considered as definitely cured. Our study on Caucasian children with NHML indicates that, from histological and clinical criteria, nearly half the cases are very similar to African BL. Even though EBV rarely associated with our cases, BL could be a worldwide lymphoma.     

Some occupational exposures as risk factors for malignant lymphomas

BACKGROUND: Malignant lymphomas (Hodgkin disease [HD] and non-Hodgkin lymphoma [NHL]) have been subject to several epidemiologic studies and found to be associated with various environmental exposures, especially solvents, wood, and phenoxy herbicides. METHODS: Various determinants for HD and NHL were evaluated in a case-referent study encompassing 31 cases of HD, 93 cases of NHL, and 204 referents, all alive. Information on these determinants, mainly occupational exposures, was obtained by mailed questionnaires. RESULTS: Crude odds ratios were increased for various occupational exposures, i.e., exposures to solvents, pesticides, metal fumes, welding, and fresh wood, and nursing. Further analyses based on logistic regression indicated exposure to phenoxy herbicides and fresh wood among sawmill workers, lumberjacks, and paper pulp workers to be significant risk factors for HD. Welding, working as a lumberjack, nursing, and ex-smoking were associated with a significantly increased risk for NHL. Radiographic examinations were negatively associated with HD, as was office work for NHL. CONCLUSIONS: The results were mainly in agreement with the findings of earlier studies, but diverging associations also appeared.     

A prospective view for the new classifications of malignant lymphomas

Malignant lymphomas, which are now apparently the neoplasms of the immune system, are not a single disease, but represent a group of entities. Because the cells of their normal counterparts undergo differentiation in a complex manner, the corresponding neoplasms are considerably heterogeneous in terms of clinicopathologic features and biologic behavior. Indeed, there are quite a few problems to be solved in the currently used classifications of malignant lymphomas. Their complexity and heterogeneity make it almost impossible, at present, to establish any single classification system which is both clinically useful and scientifically accurate. We, therefore, propose to establish separate clinical and scientific classifications. Our prospective view for the new scientific classification of malignant lymphomas is presented.     

Factors associated with the therapeutic efficacy of retinoic acids on malignant lymphomas

We recently reported the successful use of retinoic acids in the treatment of refractory lymphoma. The biologic determinants predicting response of lymphomas to retinoic acid remain unknown. This study was conducted to explore this question using in vitro models. Sensitivity of representative lymphoma cells to 13-cis-retinoic acid was determined. Sensitive and resistant cell lines were then compared for their baseline and/or retinoic-acid-regulated expression of total cellular retinoic acid binding protein, retinoic acid receptor (RAR)-alpha, RAR-beta, RAR-gamma mRNA, retinoid X receptor (RXR)-alpha, RXR-beta, RXR-gamma mRNA, transforming growth factor (TGF)-beta 1 and TGF-beta 1 receptors, and Fas (Apo-I) mRNA. The results showed that four of five T, two of three Hodgkin's, and none of six B cell lymphoma cell lines were sensitive (IC30 < 1.5 mmol/L) to 13-cis-retinoic acid. Further analyses revealed several of the above-mentioned parameters may be relevant to retinoic acid sensitivity. Baseline expression of TGF-beta 1 receptors was present in all of the five sensitive cell lines examined, but in only one of the four resistant cell lines. The correlation of Fas expression and retinoic acid sensitivity was good for B cell lines, but not apparent for T cell or Hodgkin's cell lines. On exposure to retinoic acid, an immediate and prolonged upregulation of RAR-alpha mRNA expression, lasting for more than 12 hours, occurred in all sensitive cell lines, but only minimal or transient induction was seen in resistant cells. Together, these data suggested that; 1) retinoic acid has a preferential effect on T cell and Hodgkin's lymphoma cell lines; 2) autoregulation of RAR-alpha by retinoic acids, and the presence of TGF-beta 1 receptors may be relevant to the response of lymphomas to treatment with retinoic acids.     

Chemotherapy of advanced malignant lymphomas comparative evaluation of results with single agent and combination therapy

86 patients with advanced malignant lymphomas (stage III and IV) were treated either with Vinblastine given as a single agent (49 cases) or with combination chemotherapy MOPP or COP (37 cases). In both, Hodgkin's disease and non-Hodgkin's lymphomas, induction of remission, relaps-free survival and prognostic significance of initial clinical stage were evaluated, in relation to the therapeutic modality. In patients with Hodgkin's disease, combination chemotherapy was found to produce significantly more durable remissions, when compared with single agent therapy. However, difference in the response rate, which was found to be more effective following the combination chemotherapy, was not statistically significant. In patients with non-Hodgkin's lymphomas overall lower response was recorded, regardless of the therapy applied. In all patients, better response rate and longer lasting remissions correlated with initial stage III.     

Effects of fish oil on cytokines and immune functions of mice with murine AIDS

The effects of fish oil, which is rich in n-3 fatty acids, on cytokine levels in a murine model of acquired immune deficiency syndrome (AIDS) were studied. Thirty-two C57BL/6 female mice were divided into two dietary groups and fed either a corn oil diet or a fish oil diet. After 4 weeks, each diet group was further divided into two subgroups, and mice in one subgroup were injected i.p. with LP-BM5 murine retrovirus (MAIDS) stock. After 4 weeks, all mice were killed, blood samples were collected, and the spleens and the livers were excised. Splenocytes were isolated immediately and cultured in RPMI-1640 medium and stimulated by either lipopolysaccharide (LPS) or Concanavalin A (ConA) for 24 h. The supernatant was collected for cytokine assays. The results showed that MAIDS infection increased the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1beta), while fish oil partially prevented this elevation. MAIDS infection depressed interleukin-2 (IL-2) and interferon-gamma (IFNgamma), while fish oil partially prevented the depression of IL-2. In addition, MAIDS infection depressed LPS- and ConA-stimulated cell proliferation, while fish oil partially prevented the depression. The results suggest that fish oil may slow down the progression of murine AIDS by modulating levels of cytokines including TNF-alpha, IL-1beta, and IL-2.