Effects of ecologically relevant concentrations of cadmium in a freshwater fish.

Sub-chronic effects of ecologically relevant concentrations of cadmium (Cd) were evaluated in the catfish Rhamdia quelen. The fish were exposed to Cd (0, 0.1, 1, 10 and 100µgL(-1)) for 15 days. Bioconcentration was observed in the liver of fish exposed to 10 and 100µgL(-1) of cadmium. The liver glutathione S-transferase activity decreased at 0.1 and 1µgL(-1) and increased at 100µgL(-1) and lipoperoxidation increased in all tested concentrations. Fish exposed to 0.1, 1 and 100µgL(-1) Cd presented increase in hepatic lesion index. In the kidney, the catalase activity and LPO reduced in all exposed groups. The gluthatione peroxidase, etoxiresorufin-O-deethylase activities and metallothionein increased at the highest concentration of Cd, but the level of reduced glutathione decreased. The genotoxicity was observed at 0.1 and 100µgL(-1). Neurotoxicity was not observed. The results showed that low concentrations (range of µgL(-1)) of Cd caused hepato-, nephro- and hematological alterations in this freshwater fish species.

No direct neuronotoxicity by HIV-1 virions or culture fluids from HIV-1-infected T cells or monocytes.

Macrophages and microglia are the principal target cells for human immunodeficiency virus (HIV) in brain, and as such, are likely participants in the neuropathology of HIV infection. In a model system for this process, we found that fluids from human monocyte cultures enhanced survival and differentiation of the neurons in fetal rat brain explants. In contrast, fluids from HIV-infected monocyte cultures were strongly toxic to neurons and paradoxically enhanced the proliferation of glial cells. Further, neuronotoxic activity in these fluids was mediated through activation of NMDA binding receptors on the neurons and was inhibited by any of several different NMDA antagonists. Neuronotoxic activity was directly related to contamination of the HIV virus stock with Mycoplasma arginini and M. hominis. Pure cultures of mycoplasma, bacterial lipopolysaccharide (LPS), or murine recombinant tumor necrosis factor alpha (rTNF alpha) each induced neuronotoxicity which exactly mirrored that induced by the contaminated HIV stock. It is likely that mycoplasma or components of the mycoplasma plasma membrane stimulate TNF alpha production by the glial cells in the brain explants. Indeed, careful depletion of glial cells in these explants prevented mycoplasma or LPS-mediated neuronotoxicity. No neuronotoxicity was evident with HIV-1 virus stock, HIV-1 gp120, or culture fluids from HIV-infected T cells or monocytes when these preparations were free of contamination by mycoplasma and LPS. These findings suggest caution in interpretation of those experiments in which similar contamination has not been rigorously excluded.

Tumors of pineal parenchymal cells: a correlation of histological features, including nucleolar organizer regions, with survival in 35 cases.

We studied 35 parenchymal neoplasms arising in the pineal gland, including 11 pineoblastomas, 21 pineocytomas, and three mixed pineocytoma-pineoblastomas. Pineoblastomas were most commonly found in children (mean age, 12.6 years). The median postsurgical length of survival for seven patients, including five with remote metastases, with fatal outcome was 24 months. The 21 pineocytomas were found in older individuals (mean age, 26.8 years). Four patients with pineocytoma died; two before surgery and two in the immediate postoperative period. The remaining 17 patients survived for intervals between 6 and 118 months after surgery. Two mixed pineocytoma-pineoblastomas were found in infants who died a few months after biopsy, whereas a third patient, an adult, was alive at 46 months after excision and irradiation. Both pineoblastoma and pineocytoma exhibited variable immunoreactivity to neurofilament proteins, synaptophysin, glial fibrillary acidic protein, S-100 protein, retinal-S antigen, and rhodopsin; the highest percentages of positive cells stained with synaptophysin. Three pineocytomas exhibited ganglionic differentiation and two of them also showed a glial component. Prognosis could not be correlated with the degree of divergent differentiation. Comparison of silver-stained nucleolar organizer region (AgNOR) counts between pineoblastomas and pineocytomas suggests that the former are more actively proliferative than the latter, with mixed pineocytoma-pineoblastoma showing intermediate activity. There was no correlation between AgNOR score and prognosis within the three tumor groups.

Hemangiopericytoma of the central nervous system: a review of 94 cases.

Ninety-four cases of central nervous system hemangiopericytoma (CNS-HPC) are reported. Hemangiopericytoma was found more commonly in men than in women. The mean age at diagnosis was 40.9 years for men and 47 years for women. The tumor was found throughout the entire CNS, usually superficially and closely related to the meninges. Based on multiple histologic variables, the original tumors were divided into differentiated (n = 67) and anaplastic (n = 27). Anaplastic HPC was characterized by the presence of necrosis and/or greater than five mitoses per ten 400x microscopic fields, and at least two of the following microscopic features: hemorrhage, moderate to high nuclear atypia, and moderate to high cellularity. For those patients known to be dead, median survival time was 144 months for differentiated HPC and 62 months for anaplastic HPC. Fifty-seven (60.6%) patients had one or more recurrences and metastasis developed in 22 (23.4%). Thirty-five of 56 patients with differentiated HPC had recurrence, while 22 of 26 patients with anaplastic HPC had recurrence. Bone, liver, lung, central nervous system, and abdominal cavity were the most common sites of metastasis. Postoperative radiotherapy and/or chemotherapy were significantly associated with increased patient survival time.

Systemic lymphadenopathic histology in human immunodeficiency virus-1-seropositive drug addicts without apparent acquired immunodeficiency syndrome.

We examined lymph nodes from multiple sites in 50 individuals infected with human immunodeficiency virus (HIV-1) who died accidentally of drug overdoses and in whom there was no evidence of opportunistic infection. The size, histologic pattern, presence of Warthin-Finkeldey-type giant cells, and estimation of CD4 cell count of these lymph nodes were compared with those of 13 seronegative drug addicts (controls). Lymph nodes from seropositive individuals were slightly but significantly larger than those of controls. Lymph nodes from seropositive cases were much more likely to contain secondary follicles (90%) than were those from controls (20%). Unlike follicles in control nodes, most secondary follicles in the seropositive cases were in various stages of fragmentation and involution. As follicular changes progressed, there was a decrease in CD4 cells and an increase in intrafollicular and paracortical plasma cells. Plasmacytosis was much more prevalent in lymph nodes from seropositive individuals than in controls. Warthin-Finkeldey-type giant cells were present in at least one node in 29 of 50 seropositive cases, were most numerous in those showing follicular hyperplasia with fragmentation (45% of cases), and were especially numerous in Peyer's patches (61% of cases). There was generally good concordance of HIV-1-associated follicular morphology among diverse lymph node groups. There is prolonged generalized, mild hyperplastic lymphadenopathy with frequent syncytial cells in intravenous drug addicts with asymptomatic HIV-1 infection.

Does dexamethasone suppress the Mazzotti reaction in patients with onchocerciasis?

The Mazzotti reaction is a frequent complication in patients with onchocerciasis being treated with diethylcarbamazine (DEC); and more severe manifestations of this reaction may be unacceptable in many patients. It has recently been demonstrated that prednisone modifies the severity of this reaction and reduces the microfilaricidal activity of DEC. A clinical trial was performed at the National Leprosy Training Center in Wau, Sudan, to evaluate the clinical and histologic effect of the use of corticosteroids in patients receiving DEC. Administration of a low dose of dexamethasone (3 mg/day), begun after onset of the Mazzotti reaction, modifies the progression of the Mazzotti reaction without interfering with the microfilaricidal efficacy of DEC. Pretreatment with low-dose dexamethasone--prior to beginning DEC therapy--prevents the development of the Mazzotti reaction and greatly reduces the microfilaricidal activity. Administration of diphenhydramine, after onset of the Mazzotti reaction, has no effect on the course and intensity of the Mazzotti reaction nor on microfilaricidal activity. We recommend that low-dose corticosteroids be administered in conjunction with DEC--after onset of the Mazzotti reaction--and that they be tapered rapidly.

Primary angiosarcoma of the central nervous system. Study of eight cases and review of the literature.

Angiosarcoma arising in the central or peripheral nervous system has rarely been reported. Eight patients with primary angiosarcoma of the central nervous system are described here; these included five males and three females ranging in age from 2 weeks to 72 years (mean 38 years). Of the eight neoplasms, six were located in the cerebral hemispheres and one was in the meninges; the site was unknown in the other. All patients underwent surgical resection. Five of the eight patients died, four within 4 months after surgery and one after 30 months. Two of the remaining three patients were 17 and 27 years old at the time of diagnosis and were alive at follow-up review 39 and 102 months after surgery, respectively. One patient was lost to follow-up monitoring. Microscopically, all eight tumors demonstrated a well-differentiated pattern with irregular vascular channels and intraluminal papillae; in addition, four showed poorly differentiated solid areas. Immunohistochemical staining of neoplastic cells to factor VIII-related antigen and Ulex europaeus agglutinin I was performed in five tumors and was focally positive in four. No correlation could be shown between the histological features and the growth and biological behavior of the tumors.

Computerized nuclear morphometry and survival in renal cell carcinoma: comparison with other prognostic indicators.

Morphometric nuclear parameters were compared with patient survival for a series of 174 renal cell carcinomas (RCC) collected over a 30 yr period. Stepdown regression showed long diameter, average feret diameter, form factor and the ratio of average feret diameter to equivalent diameter to be significantly associated with survival. Nuclear area, nuclear perimeter, equivalent diameter, ratio of long diameter to average feret diameter and coefficients of variation of nuclear area and nuclear perimeter were not significantly correlated with survival. All parameters were correlated with a 3 division nuclear grading classification using analysis of variance. Multivariate analysis showed nuclear form factor, tumor stage, silver staining nucleolar organizer region numbers and proliferating cell nuclear antigen expression to be independently associated with survival. The results of this study indicate that form factor is the most discriminate morphometric parameter for RCC, providing survival data additional to that derived from tumor staging and from markers of tumor proliferation.

Gold toning improves the visualization of nucleolar organizer regions in paraffin embedded tissues.

A modification of the silver colloid technique for staining nucleoar organizer regions in paraffin embedded tissues is described. This modification involves the application of a gold toning step with subsequent gold reduction, if necessary, following incubation of sections in the standard silver colloid solution. Silver stained nucleolar organizer regions (AgNORs) in toned sections are more sharply delineated when compared to untoned controls. In high grade tumors the addition of the toning step results in significantly higher AgNOR counts due to the ability to discriminate more easily individual AgNORs in argyrophilic aggregates within the nucleus. It is recommended, because of enhanced visualization, that this modification of the silver colloid technique be used in studies involving quantification of AgNORs in tissue sections.

Cystic papillary meningioma in the sella turcica of a dog.

An 8-year-old spayed Scottish Terrier was examined because of a history of intermittent abnormal behavior that progressed to hind limb ataxia and eventually to recumbency with opisthotonos. X-Ray computed tomography revealed a radiolucent mass in the area of the hypothalamus. At necropsy, a suprasellar cystic papillary meni-ngioma was identified. The unusual clinical signs of disease and computed tomographic findings of this case complicated diagnosis.

The rat epithalamus. I. Correlative scanning-transmission electron microscopy of supraependymal nerves.

Transmission and scanning electron microscopy of the rat epithalamus shows a regional variation in the distribution of supraependymal nerves (SN) which correlates well with supraependymal yellow fluorescence reported by Richards et al. (1974). The medial habenular nucleus, the intercommissural and suprahabenular recesses, the habenular commissure and the fibrae periventriculares thalami have the greatest density of SN/100micron of ependymal surface. The floor of the suprahabenular and intercommisural recesses is covered by non-ciliated ependyma. The significance of these findings is discussed with respect to (1) a direct functional relationship of SN with ependyma, and (2) a possible participation of the non-ciliated ependyma of the suprahabenular and intercommissural recesses in secretory activity whereby the CSF serves as a vehicle for neuroendocrine communication.

A histologic and immunocytochemical study of choroid plexus tumors of the dog.

Sixteen choroid plexus (CP) tumors in 12 male and four female adult dogs were analyzed microscopically. Tumors were in the lateral (six), third (six), and fourth (four) ventricles. The average age of the dogs was 6 years. Tumors were classified by the following criteria: 1) choroid plexus papilloma (CPP), which resembled normal choroid plexus and had low mitotic activity; 2) choroid plexus papilloma (CPP), which resembled normal choroid plexus and had low mitotic activity; 2) choroid plexus papilloma with atypical features (atypical CPP), which had increased cellular density, nuclear atypia, two to four mitoses per 40x microscopic field, necrosis, and infiltration of the brain parenchyma and/or leptomeninges; and 3) choroid plexus carcinoma (CPC), which had marked nuclear atypia, poorly formed papillae, greater than four mitoses per 40x microscopic field, abnormal mitotic figures, and/or extraneural metastasis. The 16 tumors were classified either as CPP or atypical CPP (none as CPC). Statistically significant associations between brain infiltration and necrosis and atypical CPP were identified. Immunohistochemical studies in 11 tumors demonstrated staining for keratin in three tumors, two of which also reacted with carcinoembryonic antigen (CEA). There was no immunoreactivity with glial fibrillary acidic protein or epithelial membrane antigen. Choroid plexus from one of three control dogs stained focally for cytokeratin only. It is concluded that normal choroid plexus and CP tumors in the dog express epithelial, but not glial differentiation.

Infections caused by Penicillium marneffei in China and Southeast Asia: review of eighteen published cases and report of four more Chinese cases.

One accidental and 17 natural human infections caused by Penicillium marneffei have been reported in the literature. The accidental infection, in Paris, followed inoculation of a culture from a Vietnamese bamboo rat into the finger of a mycologist. All patients with natural infections had lived or traveled in the Far East. Nine of these patients were Chinese, all from Guangxi Zhuang Autonomous Region. The four additional infections from Guangxi reported herein bring the total to 21 natural infections. P. marneffei is a primary pathogen of humans, causing two clinical types of disease: focal infection and fatal, progressive, disseminated infection. There are three histopathologic reactions: (1) granulomatous; (2) suppurative; and (3) anergic and necrotizing. The first two reactions are seen in patients with "normal" immunity and the third in patients with compromised immunity. P. marneffei is unique among species of Penicillium because of its thermal dimorphism, its recognized ecologic niche (restricted to the Far East), and its propensity to infect the lungs and the reticuloendothelial system and to proliferate within histiocytes.

Proliferating cell nuclear antigen (PCNA) expression as a prognostic indicator for renal cell carcinoma: comparison with tumour grade, mitotic index, and silver-staining nucleolar organizer region numbers.

Proliferating cell nuclear antigen (PCNA) expression in renal cell carcinoma (RCC) was determined by immunohistochemical staining using the PC10 clone. PCNA indices ranged from 2.4 to 53.1 per cent with mean indices of 12.6, 19.0, and 31.6 per cent for grades 1 to 3 RCC and 31.9 per cent for sarcomatoid RCC. There was a significant difference between the indices of grades 1 and 3 and grades 2 and 3 tumours and between grades 1 and 2 RCC and sarcomatoid RCC. AgNOR scores and mitotic indices were determined for each tumour and comparison of PCNA indices with mean AgNOR scores and mitotic indices showed only a weak correlation (PCNA/AgNOR r = 0.406, PCNA/mitotic index r = 0.315). Tumours were divided according to PCNA index (< or = 18 per cent and > 18 per cent) and there was a significant difference in survival between the two groups, for all cases, and for each of the Robson stages. Multivariate analysis using Cox's proportional hazard model showed PCNA index, tumour stage, and mean AgNOR score to be independent predictors of survival, while tumour grade and mitotic index were found to be dependent variables.

Acute nephropathy induced by gold sodium thiomalate: alterations in renal heme metabolism and morphology.

Gold compounds are used clinically in rheumatoid arthritis therapy. Acute renal toxicity is observed in some patients receiving chrysotherapy. The present study addresses morphofunctional and biochemical changes in rat kidneys during the first 8 days following a single ip injection of gold sodium thiomalate (AuTM), one of the gold compounds presently in clinical use. Compared to controls, AuTM pretreatment resulted in increased urine output and elevated serum creatinine and urea nitrogen concentrations. Also, by Day 8, treated rats had decreased body weights and increased kidney weights. Postmortem examination on Day 1 showed pale and mottled kidneys and diffusely pale inner cortex. Microscopically, there was severe coagulative necrosis of the proximal tubular epithelium. Epithelial regeneration was prominent by Day 4 and was nearly complete by Day 8. The regenerating epithelium was hyperplastic with basophilic cytoplasm and pleomorphic nuclei. Alterations in renal heme biosynthesis and drug metabolism paralleled the morphologic changes. The activity of delta-aminolevulinic acid dehydratase and benzo[a]pyrene hydroxylase were inhibited on Days 1, 2, and 4 following AuTM administration. Decreases in monooxygenase activity were accompanied by decreases in renal cytochrome P-450 levels. In contrast, renal microsomal heme oxygenase activity was elevated 9.5-fold on Day 1 and 2.5-fold on Day 2. By Day 8, all renal enzymatic activities assayed for were similar to those obtained with untreated rats.

Proliferation of renal cell carcinoma assessed by fixation-resistant polyclonal Ki-67 antibody labeling. Correlation with clinical outcome.

BACKGROUND: Although tumor staging is an important prognostic parameter for renal cell carcinoma (RCC), postnephrectomy survival interval is often difficult to predict for individual patients. This is the result of varied growth characteristics, which in tumors of similar stage govern both time to recurrence and rate of tumor dissemination. Polyclonal Ki-67 antibody labels a proliferation-specific antigen expressed in actively proliferating cells and is applicable to formalin fixed paraffin embedded archival tissue. This study was designed to test the prognostic utility of Ki-67 antigen labeling in a series of RCC and to compare the data with those derived from other markers of cell proliferation. METHODS: Polyclonal Ki-67 antibody staining of 206 cases of RCC was undertaken using the streptavidin-biotin method. Cases were grouped according to Ki-67 indices and Kaplan-Meier survival curves were constructed. Groups were compared in terms of survival for all cases and for each of Robson's stages using the log rank test. Further sections were stained for proliferating cell nuclear antigen (PCNA) and silver-staining nucleolar organizer regions (AgNORs). The prognostic significance of Ki-67 antigen, PCNA and AgNOR staining, histologic grade, and tumor stage were compared using Cox's proportional hazard model. RESULTS: Ki-67 immunostaining was achieved for 173 cases with indices ranging from 0.1% to 30.4%. Division of tumors with indices 6% or less and greater than 6% showed a significant difference in survival between groups for all cases and for each Robson stage. Ki-67 and PCNA indices, AgNOR scores, and tumor dissemination (Robson Stage 3 and 4) retained a significant association with survival on multivariate analysis. CONCLUSIONS: Polyclonal Ki-67 antibody immunostaining provides significant survival information that complements that derived by other markers of cell proliferation and tumor staging.

Nucleolar organizer regions in seminoma and intratubular malignant germ cells.

Nucleolar organizer regions (NORs), as demonstrated by a silver-colloid staining technique, have been counted in 71 primary testicular seminomas (typical seminoma (TS) 31, high mitotic index seminoma (HMIS) 24, and spermatocytic seminoma (SS) 16) and ten seminomas metastatic to retroperitoneal lymph nodes. Mean NOR counts were 14.36 for TS; 17.66 for HMIS; 10.89 for SS; and 17.70 for metastatic seminoma. Analysis of data using Student's unpaired t-test showed a significant difference between the NOR counts obtained from TS, HMIS, and SS. Furthermore, there was a statistically significant difference between NOR counts in metastatic seminoma when compared with TS and SS but not HMIS. The association between tumor proliferation rates and intranuclear NOR numbers is discussed. In addition to a numerical variation, the NOR distribution throughout the nucleus was noted to be different in SS when compared with the other varieties of seminoma studied. The pattern observed had some features similar to those seen in cells of the spermatogenic series. The NOR technique was also applied to 19 cases of intratubular malignant germ cells (ITMGC). It was shown that these malignant cells were easily identified using this staining method and that the NOR distribution was similar to that seen in TS and HMIS. The mean NOR count in ITMGC was 16.41. This was significantly different from that of TS but not HMIS.

Nucleolar organizer regions and prognosis in renal cell carcinoma.

The prognostic significance of nucleolar organizer regions (NORs) in renal cell carcinoma (RCC) was evaluated. NORs were quantified in a series of 182 cases of RCC using the silver-colloid method. The cases were staged according to Robson's method (48 stage I, 26 stage II, 33 stage III, 75 stage IV) and mean NOR numbers for each tumour were correlated with survival over a 5-year period. Localized tumours (stages I and II) with low NOR numbers had an almost 100 per cent 5-year survival. Those patients with clinical evidence of metastases at presentation showed a high mortality, although those with low numbers of NORs had a significantly increased disease-free interval. Statistical analysis using the log rank test indicated NORs to be a significant predictor of survival over the whole series (P = 0.0001) and within each of Robson's stages (P = 0.0008 stage I, P = 0.0154 stage II, P = 0.0009 stage III, P = 0.0001 stage IV). Analysis of data using Cox's proportional hazard model showed mean NOR numbers to be independent of stage as a predictor of survival.