Three genes specifically expressed during phosphate deficiency in<Emphasis Type="Italic"> Pholiota nameko</Emphasis> strain N2 encode hydrophobins

We previously isolated 31 cDNAs corresponding to pdi [inorganic phosphate (Pi) deficiency-inducible] genes through the differential screening of a cDNA library constructed from the mycelium of Pholiota nameko strain N2 cultured in Pi-depleted medium. Among the cDNAs, pdi251, pdi263 and pdi315 were analyzed here. The deduced amino acid sequences of pdi251, pdi263 and pdi315 showed high similarity to fungal hydrophobins and genes corresponding to these cDNAs encoding P. nameko hydrophobins were designated pnh1, pnh2 and pnh3, respectively. PNH1, PNH2 and PNH3 had a conserved spacing of eight cysteine residues in hydrophobins and a hydropathy pattern characteristic of class I hydrophobins. Phylogenetic analysis showed that PNH1, PNH2 and PNH3 were phylogenetically similar and significantly related to the hydrophobin POH1 specifically expressed in fruiting bodies of Pleurotus ostreatus. Northern blot analysis indicated that, under conditions of Pi deficiency, pnh2 and pnh3 were also induced in strains N4 and N301.Communicated by U. Kück     

Hypertension: pathophysiology and treatment

Arterial hypertension is a major cause of morbidity and mortalitybecause of its association with coronary heart disease, cerebrovasculardisease and renal disease. The extent of target organ involvement(i.e. heart, brain and kidneys) determines outcome. North Americanstudies have shown that hypertension is a major contributorto 500 000 strokes (250 000 deaths) and 1 000 000 myocardialinfarctions (500 000 deaths) per annum.     

Silencing of imprinted CDKN1C gene expression is associated with loss of CpG and histone H3 lysine 9 methylation at DMR-LIT1 in esophageal cancer

The putative tumor suppressor CDKN1C is an imprinted gene at 11p15.5, a well-known imprinted region often deleted in tumors. The absence of somatic mutations and the frequent diminished expression in tumors would suggest that CDKN1C expression is regulated epigenetically. It has been, however, controversial whether the diminution is caused by imprinting disruption of the CDKN1C/LIT1 domain or by promoter hypermethylation of CDKN1C itself. To clarify this, we investigated the CpG methylation index of the CDKN1C promoter and the differentially methylated region of the LIT1 CpG island (differentially methylated region (DMR)-LIT1), an imprinting control region of the domain, and CDKN1C expression in esophageal cancer cell lines. CDKN1C expression was diminished in 10 of 17 lines and statistically correlated with the loss of methylation at DMR-LIT1 in all but three. However, there was no statistical correlation between CDKN1C promoter MI and CDKN1C expression. Furthermore, loss of CpG methylation was associated with loss of histone H3 lysine 9 (H3K9) methylation at DMR-LIT1. Histone modifications at CDKN1C promoter were not correlated with CDKN1C expression. The data suggested that the diminished CDKN1C expression is associated with the loss of methylation of CpG and H3K9 at DMR-LIT1, not by its own promoter CpG methylation, and is involved in esophageal cancer, implying that DMR-LIT1 epigenetically regulates CDKN1C expression not through histone modifications at CDKN1C promoter, but through that of DMR-LIT1.     

Clinical usefulness of human cytomegalovirus antigenemia assay after kidney transplantation

BACKGROUND: Human (H) cytomegalovirus (CMV) infections are a major cause of morbidity and mortality among kidney transplants. We performed a prospective study to evaluate the clinical usefulness of HCMV antigenemia assay for preemptive treatment after kidney transplantation. METHODS: A total of 100 patients were followed up by HCMV antigenemia assay at posttransplantation weeks 1, 3, 5, 7, 9, 13, 17, and 21. Asymptomatic patients with positive antigenemia were observed without specific antiviral therapy. RESULTS: Most patients had been given cyclosporine A- and prednisolone-based immunosuppressive therapy (99.0%) and were HCMV seropositive before transplantation (99.0%). A positive antigenemia assay was detected in 41 patients among 97 eligible patients. Symptomatic CMV diseases were observed in 10 of 41 patients. HCMV infections were related to history of acute rejection and use of antithymocyte globulin. HCMV-related symptoms and signs were clearly correlated with the level of antigenemia. All patients who had an HCMV antigenemia titer of higher than 50 per 400,000 leukocytes developed HCMV-related symptoms and signs during the follow-up period. This criterion showed the highest positive predictive value and specificity in the development of symptomatic HCMV infection. CONCLUSIONS: Data suggest that HCMV antigenemia titer can be used as a useful guide to preemptive treatment of HCMV infection after kidney transplantation in HCMV-positive donor and recipient.     

Influence of caloric restriction on the development of atherosclerosis in nonhuman primates: progress to date

Caloric restriction (CR) has been observed to retard aging processes and extend the maximum life span in rodents. In an effort to evaluate the effect of this nutritional intervention on physiologic variables in higher species, several nonhuman primate trials are ongoing. In particular, a study evaluating the independent effect of CR on the extent of atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys. Therefore, the trial was designed to achieve identical cholesterol intake after animals were randomized to a control group or a calorie-restricted group (30% reduction from baseline caloric intake). The animals were routinely evaluated for glycated proteins, plasma insulin and glucose levels, insulin sensitivity, and specific measures for abdominal fat distribution by CT scans over a 4-year interval. The results from 4 years of intervention demonstrate that CR improves cardiovascular risk factors (such as visceral fat accumulation) and improves insulin sensitivity. In contrast to other primate studies with normolipidemic animals, CR had no independent effects on plasma lipid levels and composition in the presence of equivalent amounts of dietary cholesterol intake. Preliminary analysis of atherosclerotic lesion extent in the abdominal aorta has failed to demonstrate differences between control animals and CR animals. Follow- up studies are being conducted to determine the effect of CR on atherosclerosis extent in coronary and carotid arteries.      

Inherited disorders of 3-methylcrotonyl CoA carboxylation

The clinical course of 4 patients who had reduced activities of 3-methylcrotonyl CoA carboxylase (also called 3-methylcrotonylglycinuria) is described. Two children presented with a metabolic acidosis, one in the neonatal period and the other with episodes of acidosis that started in the second year of life. In the other 2 children neurological symptoms were prominent, one having infantile spasms and the other developmental regression with a skin rash and alopecia. Three of the children responded well to oral biotin and dietary protein restriction but the fourth, despite a biochemical response to biotin, has a severe neurological handicap. The clinical presentation of inborn errors of 3-methylcrotonyl CoA carboxylase is variable. Metabolic acidosis may not be conspicuous and instead neurological features may predominate.