Two cases of a renal epithelial tumour resembling immature nephron

Summary Two cases of renal epithelial tumours are reported in females aged 46 and 66 years respectively. In spite of the large size of the tumours, neither invasive growth nor metastasis was observed. Histologically, the tumours were composed of immature epithelial cells forming tubules with abortive glomeruloid structures. Electron microscopy of tumour cells revealed poorly developed polarity and intracytoplasmic organelles. They showed similar immunohistochemical reactions to those of developing nephrons, particularly to those of the S-shaped body. The nuclear DNA content of the tumour cells was almost euploid. We conclude that the lesions were epithelial tumours of the kidney histologically mimicking developing renal parenchyma.     

Stratum-specific likelihood ratios of the general health questionnaire in the community: help-seeking and physical co-morbidity affect the test characteristics

BACKGROUND: In evidence-based medicine, stratum-specific likelihood ratios (SSLRs) are now being increasingly recognized as a more convenient and generalizable method to interpret diagnostic information than an optimal cut-off and its associated sensitivity and specificity. We previously examined the SSLRs of the General Health Questionnaire (GHQ) in primary care settings. The present paper aims to examine if these SSLRs are generalizable to the community settings. METHODS: The Composite International Diagnostic Interview (CIDI) and the GHQ were administered on a representative sample of the Australian population in the Australian National Survey of Mental Health and Well-Being. We first compared the SSLRs of GHQ in urban Australia with the estimates that we had previously obtained from the developed urban centres in the WHO Psychological Problems in General Health Care study. If the SSLRs in the community were found to differ significantly from those in the primary care, we sought for explanatory variables. RESULTS: The SSLRs in urban Australia and in the urban centres in the WHO study were significantly different for three out of the six strata. When we limited the sample to those with physical problems who visited a health professional, however, the SSLRs in the Australian study were strikingly close to those observed for primary care settings. CONCLUSIONS: Different sets of SSLRs apply to primary care and general population samples. For general population surveys in developed countries, the results of the Australian National Survey represent the currently available best estimates. For developing countries or rural areas, the results are less definitive and an investigator may wish to conduct a pilot study.     

Mesp1-nonexpressing cells contribute to the ventricular cardiac conduction system.

Previous fate mapping analysis, using Cre recombinase driven by the Mesp1 locus, revealed that Mesp1 is expressed in almost all of the precursors of the cardiovascular system, including the endothelium, endocardium, myocardium, and epicardium. Mesp1-nonexpressing cells were found to be restricted to the outflow tract cushion and along the interventricular septum (IVS), which is a location that is suggestive of specialized cardiac conduction system (CCS). In our current study, we examined the identity of these IVS cells by using the pattern of beta-galactosidase activity in CCS-lacZ mice. In addition, by crossing Mesp1-Cre and floxed GFP reporter mice with CCS-lacZ mice, we have calculated that approximately 20% of the ventricular CCS within the IVS corresponds to Mesp1-nonexpressing cells. These data suggest that the ventricular CCS is of heterocellular origin. Furthermore, we indicate a possibility that a population of the cells that contribute to the ventricular CCS might be distinguished at an early stage of development.     

Enhanced poliovirus replication in cytomegalovirus-infected human fibroblasts.

Replication of poliovirus in human cytomegalovirus (CMV)-infected cells is enhanced 5-to 10-fold over replication in uninfected cells. Enhanced poliovirus replication in dually infected cells was not due to a difference in adsorption on infected cells and was supported by evidence of increased synthesis of polio-specific RNA. A functional CMV genome appeared to be required for the enhancement of polio replication since enhanced replication was not seen in cells infected with uv-irradiated CMV or in cultures treated with the inhibitors of CMV replication. Enhanced polio replication in CMV-infected cells may be due to the enhanced cellular metabolism in these cells.     

Exclusion of SMAD4 mutation as an early genetic change in human pancreatic ductal tumorigenesis

Pancreatic ductal carcinoma is one of the malignant diseases with the poorest prognosis. To develop effective methods for better treatment of pancreatic cancer patients, we tried to analyze the course of multistep carcinogenesis of the pancreatic ductal cells. IPMT (intraductal papillary-mucinous tumor) is thought to be one of the premalignant lesions of the pancreas, which would transform into carcinomas. Loss of 18q at the SMAD4 locus is known to be an early genetic change in pancreatic ductal carcinomas. It is not clear, however, whether or not the target gene for inactivation is SMAD4. Using 18 IPMTs, we analyzed LOH at the SMAD4 locus and observed frequent LOH (7/14, 50%). No mutations were observed in any of the tumors. Moreover, the expression level of the SMAD4 protein did not show a reduction in IPMTs. These results suggested that (i) inactivating mutation of the SMAD4 gene is a rather late genetic change in pancreatic carcinogenesis, and (ii) there may be an unknown tumor suppressor gene in 18q, other than SMAD4, that is involved in pancreatic ductal carcinogenesis.     

Role of cytokines in autoimmune myocarditis and cardiomyopathy

Cellular as well as humoral autoimmune responses are critically associated with the pathogenesis and progression of myocarditis and cardiomyopathy. Cytokines appear to play critical roles in accentuating or regulating autoimmune mechanisms in these disorders. However, depending on the triggers of autoimmune responses against the heart, such as viral or parasitic infections and experimental immunization with cardiac myosin, the effect of each cytokine on autoimmune myocardial disease may vary. Cytokines may represent new therapeutic targets in the treatment and prevention of autoimmunity-mediated myocarditis and cardiomyopathy, though the etiology and variability in the type of autoimmune responses should be taken into account in the development of cytokine/anti-cytokine treatment of these disorders.     

Die biochemische Frühdiagnose der Cystinose aus kultivierten Fibroblasten

Zusammenfassung Mit Hilfe der kultivierten Fibroblasten aus Hautbiopsiematerial gelingt es, vor dem Auftreten anderer biochemischer Veränderungen zu klären, ob in einer mit Cystinose belasteten Familie ein junger Säugling, der noch keine klinischen Symptome bietet, an Cystinose leidet. Das Cystin erreicht in den Fibroblasten Cystinosekranker Konzentrationen von etwa 5–11 Mol1/2 Cystin/g Protein, während normale Fibroblasten nur Spuren von Cystin enthalten. Damit ist eine verläßliche Methode zur Frühdiagnose gegeben, die eine diätetische Therapie zu einem Zeitpunkt erlaubt, wo die irreversible Tubulopathie noch gering ist.

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Summary It is possible to diagnose cystinosis in young infants from families, where cystinosis is known, by culturing fibroblasts from skin biopsy material before any biochemical or clinical symptoms are evident. Fibroblasts from patients suffering from cystinosis show a high content of about 5–11 Mol1/2 cystine/g protein, while normal fibroblasts only have traces of cystine.This is a very reliable method for early diagnosis and dietetic therapy can be started before any damage has been done to the tubuli.