Sex related differences in serum gastrin concentrations and G- and D-cell populations of the gastric mucosa in guinea-pigs (experimental RIA and immunocytochemical study).

In the present study antral G-cells which secrete gastrin and antral and fundic D-cells which secret somatostatin, an inhibitor of gastric acid secretion were revealed immunocytochemically and the population size estimated along with serum gastrin levels in ten male and eight female guinea pigs. Serum gastrin, antral G-cells, antral D-cells and fundic D-cells were 41.90 +/- 6.10 SD pg/ml, 210 +/- 18.03 SD cells/cm, 128.20 +/- 17.64 SD cells/cm and 121 +/- 17.91 SD cells/cm respectively in males and 35 +/- 4.62 SD pg/ml, 176 +/- 13.80 SD cells/cm, 108.40 +/- 6.90 SD cells/cm and 106.8 +/- 6.50 SD cells/cm respectively in females. The differences in serum gastrin levels, antral G-cell population and antral D-cell population between the two sexes were statistically significant (P less than 0.05, P less than 0.001, P less than 0.01). It is possible that endogenous androgens induce a relative hyperplasia and endogenous oestrogens a relative hypoplasia of G-cells. Antral D-cell differences may reflect an adaptive hormonal mechanism to the possible different states of gastric secretory functions.     

Ontogeny of intrinsic innervation in the human kidney

We aimed to define, for the first time, the ontogeny of intrarenal innervation and to assess the distribution and nature of parenchymal nerves in the human fetal kidney. Our material consisted of routinely-processed renal tissue sections from 17 human fetuses, six of 20–24 gestational weeks (gw) and 11 of 25–40 gw, and three adults. We used immunohistochemistry with antibodies to the pan-neural markers neuron-specific enolase (NSE), neurofilaments (NF), PGP9.5, S100, and the adrenergic marker tyrosine hydroxylase (TH). NSE-, NF-, S100-, and PGP9.5-positive nerves, associated with arterial and venous vasculature, were identified in the renal cortex from 20 gw onwards, and their density appeared to increase with gestation, reaching adult levels at 28 gw. Most of the intrarenal nerves were TH-positive. Nerve fibers extended from the corticomedullary region to the outer cortex, reaching the renal capsule in the 3rd trimester. In detail, NSE-, NF-, S100-, PGP9.5-, and TH-immunoreactive fibers were observed in close apposition to the renal artery and its branches, occasionally reaching the afferent and efferent arteriole (3rd trimester). Nerve fibers were detected in close apposition to the juxtaglomerular apparatus in the 2nd and 3rd trimesters. In the renal medulla, NSE-, PGP9.5-, S100-, and TH-positive nerve fibers were detected close to tubular cells as early as 20 gw. However, their density gradually decreased during the 3rd trimester, and they were not observed in the medulla of the adult kidney. In conclusion, the human fetal kidney appears richly innervated during the 2nd and 3rd trimesters. There is a progressive increase in the density of parenchymal nerve fibers towards term from the corticomedullary region to the cortex. Most intrarenal nerves are adrenergic and have a predominant perivascular distribution, implying that renal innervation plays an important functional role during intrauterine life.     

Expression of metallothionein in lung carcinoma: correlation with histological type and grade

AIMS: Over-expression of cellular metallothionein occurs frequently in human tumours but the underlying mechanism remains unknown. The aim of this study was to assess metallothionein expression in cases of lung carcinoma and to correlate it with histopathological parameters. METHODS AND RESULTS: Tumour tissue samples from 89 patients with lung carcinoma were immunostained by the streptavidin-biotin-peroxidase technique, using a monoclonal antibody against both metallothionein-1 and -2 isoforms. Positive matallothionein immunostaining was prominent in 44 out of 89 (49%) and negative in 45 out of 89 (51%) cases of lung carcinoma examined. Metallothionein positivity was prominent in 32 out of 43 (74%) cases of squamous cell lung carcinoma, and in 12 out of 35 (34%) cases of adenocarcinoma, while it was negative in all 11 cases of small-cell lung carcinoma examined, presenting a statistically significant difference between the different histological types. The intensity of metallothionein staining revealed a statistically significant difference between the squamous cell and adenocarcinoma cases examined. The pattern and extent of metallothionein staining in tumour cells and the expression of metallothionein in stromal cells were not correlated with histopathological parameters (type and grade) in metallothionein-positive cases of lung carcinoma examined. No association was found between metallothionein expression and lymph node status in the examined cases of lung carcinoma. CONCLUSIONS: Our findings indicate that expression of metallothionein was evident in squamous cell lung carcinoma and adenocarcinoma, but absent in small-cell lung carcinoma, supporting evidence for participation of this protein in the biological mechanisms underlying the carcinogenic evolution in the lung.     

Assessment of mycobacterial,propionibacterial, and human herpesvirus 8 DNA in tissues of greek patients with sarcoidosis

The causes of sarcoidosis are unknown. In this study, we report the presence of Mycobacterium tuberculosis complex and Propionibacterium granulosum DNA in a significant proportion of Greek patients with sarcoidosis. Human herpesvirus 8 DNA was not detected in sarcoid tissues from Greek patients. Our findings are discussed.     

p53, c-myc p62 and proliferating cell nuclear antigen (PCNA) expression in non-Hodgkin's lymphomas.

AIMS--To investigate the immunohistochemical expression of p53 protein in non-Hodgkin''s lymphomas (NHL) and its relation to that of c-myc p62 oncoprotein and proliferating cell nuclear antigen (PCNA). METHODS--Paraffin wax embedded tissue from 90 non-Hodgkin''s lymphomas (72 B cell and 18 T cell) was stained immunohistochemically for p53 protein, c-myc p62 oncoprotein, and PCNA using the monoclonal antibodies DO7, c-myc 1-9 E10, and PC-10, respectively. RESULTS--Of the non-Hodgkin''s lymphomas studied, 55 (61%) stained positively for p53 protein. The proportion of positive cases increased from low grade non-Hodgkin''s lymphoma and was higher in tumours of T cell origin. The percentage of positive cells (labelling index or LI) was significantly lower in low grade non-Hodgkin''s lymphoma, but no difference was established between intermediate and high grade non-Hodgkin''s lymphoma. In a large proportion of low grade non-Hodgkin''s lymphoma the LI was below 1%. c-myc p62 immunoreactivity was identified in all cases. A significant positive correlation was established between p53 LI and c-myc p62 LI (rs = 0.453) as well as between p53 LI and PCNA LI (rs = 0.338). CONCLUSIONS--p53 immunoreactivity was present in about half the cases of non-Hodgkin''s lymphoma and was related to the grade of malignancy and possibly to the B or T cell origin of the tumour. It was also associated with the proliferation state as expressed by PCNA LI and c-myc p62 expression, indicating that the expression of these three cell cycle-related genes might be interrelated.     

Primary gastrointestinal malignant lymphomas. A morphologic and immunohistochemical study

Thirty-nine primary gastric and 22 intestinal malignant lymphomas collected from 1969 to 1980 have been studied morphologically and immunohistochemically. Eighteen of the 61 gastrointestinal lymphomas were of low-grade malignancy (9 lymphoplasmacytoid/cytic, 3 centrocytic, 6 centroblastic/centrocytic) and 43 were of high-grade malignancy (14 centroblastic, 7 lymphoblastic, 22 immunoblastic malignant lymphomas) according to the Kiel classification. The peroxidase-antiperoxidase (PAP) method was used in 53 of the 61 cases. Twenty-seven of them revealed a monoclonal positivity for intracytoplasmic IgS: kappa light chains in 18 and lambda light chains in 7 cases. Two cases represented alpha chain disease, revealing only a heavy chain positivity. The most frequent staining pattern of the lymphoma cells was that of kappa/mu. Cells with a mixed centrocytic and plasma cell configuration (centrocytoid plasma cells) proved to be positive for intracytoplasmic IgS. Lymphoma cells of all tested cases proved to be negative for all histiocytic markers. Histologically and immunohistochemically, the Greek cases of primary gastrointestinal malignant lymphomas seem to resemble "western" type lymphomas.     

Expression of Epstein-Barr virus latent membrane protein-1 in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma: associations with presenting features, serum interleukin 10 levels, and clinical outcome.

PURPOSE: EBV-latent membrane protein-1 (LMP-1) is often expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's lymphoma (cHL), but its clinical significance is controversial. We correlated LMP-1 with presenting features, including serum interleukin 10 levels and clinical outcome. EXPERIMENTAL DESIGN: Patients were eligible if they had biopsy-proven cHL, were untreated, HIV-1 negative, and had available archival tissue. LMP-1 expression was determined by immunohistochemistry. RESULTS: We identified 577 patients with cHL with a median age of 30 years, 55% of whom were male. LMP-1 was expressed in HRS cells of 124 patients (21%) and was detected in 78 of 461 (17%) patients with nodular sclerosis compared with 44 of 112 (39%) with mixed cellularity (P < 0.001 by Fisher's exact test). Patients with tumors with LMP-1-positive HRS cells had higher serum interleukin 10 levels (P = 0.009 by Mann-Whitney test). For the 303 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens, the 5-year failure-free survival (FFS) for those with LMP-1-positive tumors was 74% compared with 81% for those with LMP-1-negative tumors (P = 0.23, by log-rank test). Overall survival (OS) at 5 years for patients with LMP-1-positive tumors was 90 versus 91% for patients with LMP-1-negative tumors (P = 0.8 by log-rank test). Expression of LMP-1 was not associated with different FFS and OS in patients treated with other regimens or with radiotherapy alone. CONCLUSIONS: LMP-1 was expressed by HRS cells in 21% of cHL and correlated with mixed cellularity type and higher serum interleukin 10 levels. The presence of LMP-1 was not associated with FFS or OS in uniformly treated patients.     

A morphometric study of bone marrow angiogenesis in hairy cell leukaemia with clinicopathological correlations

Bone marrow angiogenesis has recently been implicated in the pathophysiology and course of various haematological malignancies. Little is known, however, about the significance of this phenomenon in hairy cell leukaemia (HCL). We evaluated various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemistry, in the bone marrow of 44 patients with typical HCL, before and after treatment with interferon-alpha (IFN-alpha). Overall, bone marrow from 103 HCL patients and 20 controls was examined. Microvessel density (MVD) and several size- and shape-related parameters were quantified in the region of most intense vascularization using image analysis. MVD, size-related parameters and the percentage of branching microvessels were higher in HCL than in controls. Likewise, perimeter counts were higher in partial/non-responders than in complete responders. Achievement of complete response was accompanied by smaller calibre microvessels. IFN-alpha induced a decrease in MVD and branching values in cases with diffuse marrow involvement. In univariate analysis, progression-free survival was adversely affected by MVD, branching and major axis length. Multivariate analysis indicated that MVD/branching independently affected progression-free survival and the likelihood of complete response. Our data suggest that the generation of bone marrow microvessels indicated an increased risk of progression and IFN-alpha treatment failure in HCL. Furthermore, the prognostic significance of angiogenesis requires the concomitant assessment of MVD and the complexity of the microvascular network.     

Forced swimming differentially affects male and female brain corticosteroid receptors

Corticosteroid receptors are key mediators of the neuroendocrine response to stress. Previously, we have determined the effects of restraint stress on the regulation of corticosteroid receptor genes in the brain and pituitary of male and female rats. Significant gender- and regional-specific regulation of receptor mRNAs was observed. To further investigate the stressor specificity in the same context, we have determined glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) mRNAs following exposure to swimming stress paradigms applied alone, or in combination with restraint stress. Our data revealed stressor-specific alterations in GR or MR mRNA levels, which were more pronounced in males, the gender most affected by swimming stress. No alterations in GR or MR mRNA levels were detected in the female hippocampus and hypothalamus upon exposure to swimming paradigms, while in males the same stressors down-regulated GR mRNA in the hippocampus (chronic exposure) and up-regulated both genes in the hypothalamus (acute exposure). In the frontal cortex, acute swimming stress caused a reciprocal change in GR mRNA levels in the two sexes. The above difference is not due to circulating ovarian steroids, since ovariectomy did not change the female pattern of GR gene expression following acute stress. Our results further showed a hypothalamic-pituitary-adrenal axis facilitation to a novel superimposed stressor expressed at the level of limbic corticosteroid receptors: When chronically restrained rats of both sexes were exposed to acute swimming stress, a reduced GR/MR mRNA ratio, implying reduced feedback axis sensitivity, was detected in both the hippocampus and the hypothalamus. In conclusion, our work provides additional evidence on stressor, gender and region specificity in the regulation of brain corticosteroid receptors.