Mycobacterium bovis with different genotypes and from different hosts induce dissimilar immunopathological lesions in a mouse model of tuberculosis.

With the hypothesis that genetic variability of Mycobacterium bovis could influence virulence and immunopathology, five M. bovis strains were selected from an epidemiological study in Argentina on the basis of their prevalence in cattle and occurrence in other species. We then determined the virulence and the immunopathology evoked by these strains in a well-characterized mouse model of progressive pulmonary tuberculosis. The reference strain AN5 was used as a control. BALB/c mice infected with this M. bovis reference strain showed 50% survival after 4 months of infection, with moderate bacillary counts in the lung. Two weeks after inoculation, it induced a strong inflammatory response with numerous granulomas and progressive pneumonia. In contrast, strain 04-303, isolated from a wild boar, was the most lethal and its most striking feature was sudden pneumonia with extensive necrosis. Strain 04-302, also isolated from wild boar but with a different spoligotype, induced similar pathology but to a lesser extent. In contrast, strains 534, V2 (both from cattle) and 02-2B (from human) were less virulent, permitting higher survival after 4 months of infection and limited tissue damage. Strain AN5 and the cattle and human isolates induced rapid, high and stable expression of interferon (IFN)-gamma and inducible nitric oxide synthase (iNOS). In contrast, the more virulent strains induced lower expression of IFN-gamma, tumour necrosis factor-alpha and iNOS. Interestingly, these more virulent strains induced very low expression of murine beta defensin 4 (mBD-4); whereas, the control strain AN5 induced progressive expression of this anti-microbial peptide, peaking at day 120. The less virulent strains induced high mBD-4 expression during early infection. Thus, as reported with clinical isolates of M. tuberculosis, M. bovis also showed variable virulence. This variability can be attributed to the induction of a different pattern of immune response.

[Leiomyosarcoma associated with Epstein-Barr virus in an adult with renal transplant]. / Leiomiosarcoma asociado con el virus de Epstein-Barr en un adulto con trasplante renal.

Recently the association between the Epstein-Barr virus (EBV) and smooth muscle lesions has been described in immunosuppressed children but it is infrequent in adults. The role of EBV in the pathogenesis of these lesions is obscure. We presents a 28 year old man with end stage renal disease transplanted in 1994. Two years later he developed several nodular lesions that affected both lungs, liver, spleen, retroperitoneal ganglia and the left thigh; one year later he died. The surgical specimen from the thigh and a liver biopsy were diagnosed as leiomyosarcoma. Immunohistochemical reactions against vimentin and smooth muscle actin were positive. In situ hybridization disclosed positivity against EBV nuclear antigens (EBNA-2) in neoplasic cells. This is the first case of sarcoma in transplanted patients of our institution and represents a rare case of leiomyosarcoma associated with EBV in adults.

Perinatal administration of testosterone induces hypertrophy of the anterior commissure in adult male and female rats.

A possible sex difference in the mean sagittal area of the anterior commissure (AC) was investigated in normal, newborn-castrated, and perinatally-androgenized rats. A second experiment included castrated adult rats from each sex exposed to testosterone twelve days before sacrifice. In normal rats, as well as in those exposed to testosterone as adults, no quantitative difference was found in the AC. However, perinatal exposure to testosterone induced a 20-25% increase in the mean area of the AC of rats from each sex. It is proposed that gonadal sex steroids may have a reciprocal influence upon the structure of central olfactory pathways, due to the influences of the main olfactory system upon gonadotropin secretion.

Histological and subcellular distribution of 65 and 70 kD heat shock proteins in experimental nephrotoxic injury.

The cellular distribution of 65 and 70 kD heat shock proteins (HSPs) was studied in the normal rat kidney and after acute tubular necrosis (ATN) induced by inorganic mercury (HgCl2). In the normal kidney the 65 kD HSP was found in the cytoplasm of podocytes and proximal convoluted tubules, whereas the 70 kD HSP was located in nuclei and cytoplasm of podocytes, cortical convoluted, and collecting tubules. The distribution of both HSPs along ATN changed as a function of time. In the early phase, before evidence of histological damage, both HSPs were found in the pielocaly ceal epithelium and medullary collecting tubules. During the necrotic phase, HSPs coexisted with sites of severe damage (i.e. cortical tubules). With immunoelectron microscopy damaged cells showed an abundance of 65 kD HSP-I in mitochondria, as well as in chromatin and nucleoli, while 70 kD HSP-I was overexpressed in the cytoplasm, mito chondria, lysosomes, cytoskeleton, chromatin, and nucleoli, and coincided with urinary excretion of HSPs. In the postregenerative phase, the distribution of HSPs was similar to that found in the normal kidney. HSPs of 65 and 70 kD were encountered constitutionally and their immunolabeling is correlated with the magnitude of cell injury.

[High prevalence of the Epstein-Barr virus in a Mexican population with Hodgkin's disease]. / Prevalencia alta del virus de Epstein-Barr en una población mexicana con enfermedad de Hodgkin.

The Epstein-Barr virus (EBV) has been demonstrated in association with cases of Hodgkin's disease (HD) indicating that, in at least in some cases, EBV may play a pathogenic role in the development of HD. To determine the prevalence of EBV in HD in a Mexican adult population, we studied 39 formalin-fixed and/or B-5, paraffin embedded samples of patients with HD, by immunoperoxidase; in situ hybridization was done in 32 of the 39 cases. We analyzed the presence of the latent membrane protein (LMP) and EBV-specific DNA sequences. Reed-Sternberg cells and mononuclear variants were positive for LMP in 28 cases (72%). LMP staining was found both on the cell surface and/or within the cytoplasm with enhancement in the Golgi area. The LMP was found in the single case of diffuse lymphocyte predominant HD, in 6/12 cases of nodular sclerosis (50%), in 10/15 cases of mixed cellularity (67%) and in all eleven cases of lymphocyte depleted HD (100%). No EBV-specific DNA sequences were found by in situ hybridization. Our results show: 1) a higher association of EBV in our population compared to the approximately 48% reported in developed countries; 2) all histologic subtypes of HD in Mexico appear to be strongly associated with EBV in contrast to the strong association with only mixed cellularity seen in Western populations; 3) the high prevalence of EBV in HD in Mexico may be a function of histology, ethnic groups, socioeconomic factors and/or geography.

Evidence of a direct projection of the vomeronasal organ to the medial preoptic nucleus and hypothalamus.

In rodents the vomeronasal system plays an important role in modulating the hypothalamic control of gonadotropin secretion. It is accepted that the anatomical pathways by which the vomeronasal organ influences the neuroendocrine aspects of the reproductive behavior involves a polysynaptic system, including the accessory olfactory bulb, the 'vomeronasal amygdala', the bed nucleus of the stria terminalis and medial preoptic and ventromedial hypothalamic nuclei. We found that 72 h after unilateral transection of the vomeronasal nerves of an ipsilateral orthograde degeneration is seen in the neuropil of the medial preoptic, ventromedial, and arcuate hypothalamic nuclei. This represents an anatomical evidence of a monosynaptic link between the vomeronasal neuroepithelium and the medial preoptic nucleus, and hypothalamus.

Ultrastructural and immunocytochemical study of a primary gastrinoma of the liver.

A primary hepatic gastrinoma found in a 13-year-old boy was studied by light microscopy, immunohistochemistry, electron microscopy, and immunoelectron microscopy. Results were consistent with a neuroendocrine neoplasm with abundant gastrin-immunoreactive cells. Unlike all previously reported cases of primary hepatic neuroendocrine tumors, which have been endocrinologically asymptomatic, the patient had a Zollinger-Ellison syndrome apparently cured by surgical resection of the tumor.

Rapeseed diet and hepatocyte hypertrophy: an experimental morphometric study.

A previous study suggested that a rapeseed diet induced hepatocellular hypertrophy in normal albino rats. In the present study morphometry confirmed that a rapeseed diet produces hepatocytic hypertrophy which, according to cytological findings, is primarily due to an increase in the cytoplasmic area. A combination of a rapeseed diet and the administration of carbon tetrachloride (CCl4) also led to hepatocellular hypertrophy but the histological picture of the cirrhosis was similar to the one in control animals receiving CCl4 alone. The fact that the hypertrophy was primarily due to organelles supports the idea that a component or components of the rapeseed may modify protein turnover in the parenchyma of the liver.