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PubMed1990

[Stomach cancer mortality and nutrition intake in northern Japan--especially on relation to sodium chloride].

There is a big difference on the stomach cancer (SC) mortality between the north-western and the north-eastern parts of Honshu (mainland of Japan) although not much differences on cerebrovascular disease (CVD) mortality can be observed between these two areas while both of these diseases are said to be related to high-salted diets. The relation between diet and age-adjusted mortality of SC and CVD in northern Honshu was examined here, based on the results of the nutrition survey carried out by prefecture office (1971-87, 6 prefectures, total of 18 data sets). The results are summarized as follows: 1. There are no significant differences on salt intake between the north-western and the north-eastern parts of Honshu. 2. Intake of milk and dairy products is negatively related to SC. 3. Intake of animal protein is negatively related to CVD.

Diet↗
PubMed1990

Proteolytic processing of porcine big endothelin-1 catalyzed by cathepsin D.

Cathepsin D, a candidate for endothelin-converting enzyme (ECE), was allowed to act on porcine big endothelin-1 (big ET-1, 1-39). The proteinase primarily cleaved the Asp18-Ile19 and Trp21-Val22 bonds of big ET-1(1-39), with a optimum pH of 3.5. The mature ET-1(1-21), generated by the cleavage between Trp21 and Val22, was subsequently degraded by removal of most of the C-terminal tripeptide (Ile19-Ile20-Trp21). Therefore, cathepsin D is by no means a specific ECE, although the proteinase does cleave the Trp21-Val22 bond of big ET-1(1-39) to produce mature ET-1(1-21). The possibility that cathepsin D can act as an endothelin-degrading enzyme in vivo warrants consideration.

Amino Acid Sequence↗
PubMed2006

Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better?

Genetic epidemiology, including twin studies, provides robust evidence that genetic variation in human populations contributes to susceptibility to infectious disease. One of the major limitations of studies that attempt to identify the genes and mechanisms that underlie this susceptibility has been lack of power caused by small sample size. With the development of novel technologies, burgeoning information on the human genome, the HapMap project, and human genetic diversity, we are at the beginning of a new era in the study of the genetics of complex diseases. This review looks afresh at the epidemiological evidence that supports a role for genetics in susceptibility to infectious disease, examines the somewhat limited achievements to date, and discusses current advances in methodology and technology that will potentially lead to translational data in the future.

Communicable Diseases↗
PubMed2001

Radiographic appearance of sesamoid bones in the hands and feet of Malawian subjects.

Our aim was to determine the prevalence of sesamoid bones in adult black Malawians from radiographs of the hands and feet. A total of 255 radiographs from 85 men and 45 women aged 16-66 years were used: 126 of the hands and 129 of the feet. All the hand films revealed one sesamoid bone at the interphalangeal joint and two at the metacarpophalangeal joint of the thumb. All the foot films showed two sesamoid bones at the metatarsophalangeal joint of the big toe. Occasional sesamoid bones were found at the metacarpophalangeal and metatarsophalangeal joints of the index finger and the small toe, respectively. Only 4.8% of the hands had sesamoid bones at the metacarpophalangeal joint of the index finger, compared with reported percentages of between 35% and 64.2% in Caucasians. The present study also records, probably for the first time in Africans, an incidence of 10.8% of sesamoid bones occurring at the metatarsophalangeal joint of the small toe, which again is at variance with the reported range of 5.5-10% in Caucasians. This study provides anatomical data that will help in the diagnosis and management of disorders of sesamoid bones which are often overlooked in Africans.

Adolescent↗
PubMed2003

Stimulation of transepithelial Na(+) current by extracellular Gd(3+) in Xenopus laevis alveolar epithelium.

In the present study we investigated the effect of extracellular gadolinium on amiloride-sensitive Na(+) current across Xenopus alveolar epithelium by Ussing chamber experiments and studied its direct effect on epithelial Na(+) channels with the patch-clamp method. As observed in various epithelia, the short-circuit current ( I(sc)) and the amiloride-sensitive Na(+) current ( I(ami)) across Xenopus alveolar epithelium was downregulated by high apical Na(+) concentrations. Apical application of gadolinium (Gd(3+)) increased I(sc) in a dose-dependent manner ( EC(50) = 23.5 microM). The effect of Gd(3+) was sensitive to amiloride, which indicated the amiloride-sensitive transcellular Na(+) transport to be upregulated. Benz-imidazolyl-guanidin (BIG) and p-hydroxy-mercuribenzonic-acid (PHMB) probably release apical Na(+) channels from Na(+)-dependent autoregulating mechanisms. BIG did not stimulate transepithelial Na(+) currents across Xenopus lung epithelium but, interestingly, it prevented the stimulating effect of Gd(3+) on transepithelial Na(+) transport. PHMB increased I(sc) and this stimulation was similar to the effect of Gd(3+). Co-application of PHMB and Gd(3+) had no additive effects on I(sc). In cell-attached patches on Xenopus oocytes extracellular Gd(3+) increased the open probability ( NP(o)) of Xenopus epithelial sodium channels (ENaC) from 0.72 to 1.79 and decreased the single-channel conductance from 5.5 to 4.6 pS. Our data indicate that Xenopus alveolar epithelium exhibits Na(+)-dependent non-hormonal control of transepithelial Na(+) transport and that the earth metal gadolinium interferes with these mechanisms. The patch-clamp experiments indicate that Gd(3+) directly modulates the activity of ENaCs.

Animals↗
PubMed1986

Carbon-14 in low-level radioactive waste from two nuclear power plants.

The amount of 14C in low-level radioactive wastes is important for determining the future impacts of their disposal. New regulations in the Code of Federal Regulations, Title 10, Part 61 (10 CFR 61) require quantitation of 14C and other radionuclides in such wastes not amenable to measurement by gamma spectroscopy. Sampling was done of major waste streams at the Palisades pressurized water reactor (PWR) and the Big Rock Point boiling water reactor (BWR) to determine quantities of 14C in the waste streams for comparison with other reported studies. Analyses were performed by releasing all 14C constituents in the waste samples in the form of 14CO2 by chemical processing or by heating the samples in a tube furnace containing CuO2 catalyst and trapping the evolved gas in a liquid scintillator for counting. The largest amounts of 14C were found in the resins and filters used for reactor water cleanup, a result which is similar to those of the available studies. From these data, the annual amounts of 14C in wastes from nominal PWRs and BWRs were estimated to be 4.7 and 0.5 Ci/GW(e)-yr, respectively.

Carbon Radioisotopes↗
PubMed2000

Endothelin-1 inactivating peptidase in the human kidney and urine.

OBJECTIVE: Recently, an apparently novel, specific endothelin-1 inactivating metalloendopeptidase (ET-1 peptidase) has been isolated from the rat kidney. In this study we attempted to determine whether the same or a similar peptidase is present in the human kidney, and whether the enzyme is excreted into the urine. The urinary ET-1 peptidase could serve as an indirect index of the renal endothelin system, both in physiology and pathophysiology. METHODS: Kidney specimens were obtained from part of nephrectomized kidneys unaffected by any neoplastic process from six adult patients. The enzyme was purified using differential centrifugation, detergent solubilization of the membrane proteins, ultrafiltration and nondenaturing gel electrophoresis. The enzyme activity assays were performed at pH 5.5 and 37 degrees C in the presence of increasing concentrations of unlabelled peptides and inhibitors using a fixed amount of [125I]ET-1 as substrate. The degradation extent was quantified with trichloroacetic acid precipitation and high performance liquid chromatography. The degrading activity of ET-1 was determined in urine samples from adult patients with hypertension, children with chronic renal failure and those with stable renal allograft RESULTS: ET-1 peptidase from the human kidney displays characteristics close to that of the rat ET-1 peptidase we have recently described (J. Hypertens 1994; 12:1155-1162). The enzyme, a membrane-bound metalloendopeptidase, exhibits low electro- phoretical mobility on nondenaturing gel (Rf 0.08); it is an apparently heterologous structure comprising three enzymatically inactive subunits, it has a pH optimum at 5.5, a nanomolar range affinity to the ET-1 (KM 180 nmol/l) that is hydrolysed to two main degradation products, and a 10-100-fold lower affinity to big ET-1 (KM 11.5 micromol/l), endothelin 11 21 fragment (KM 15.3 micromol/l), endothelin antagonist Trp-Leu-Asp-Ile-Ile-Trp (KM 3.1 micromol/I), gastrin (KM 2.2 micromol/l) and cholecystokinin (KM 4.0 micromol/l). Substance P, neuropeptide Y, atrial natriuretic peptide, bradykinin, angiotensin II and enkephalin were poor substrates for the enzyme. The most powerful inhibitors of the ET-1 peptidase included thiorphan (IC50 0.28 nmol/l), phosphoramidon (IC50 0.55 nmol/l), phenanthroline (IC50 11.5 micromol/l), cyclosporin (IC50 400 micromol/l), phosphate (IC50 1.2 mmol/l), citrate (IC50 0.6 mmol/l) and aniline naphthalene sulphonic acid (IC50 0.25 mmol/l). Our data suggest that three ET-1 degrading peptidases with optimal activity at pH 4.5, 5.5 and 7.0, respectively, are excreted into the urine. The enzyme with a pH optimum 4.5 is of lysosomal origin whereas the two other enzymes correspond by their pH optima to the renal ET-1 peptidase and neutral endopeptidase. We have found statistically significant increases (P < 0.001) in the activity of both lysosomal and ET-1 peptidase in the urine in patients with hypertension and in children with chronic renal failure compared with healthy subjects or children with stable renal allograft CONCLUSIONS: Human kidney contains an acidic, highly specific endothelin-1 inactivating metalloendopeptidase that may have a key role in the regulation of concentrations of renal and circulating endothelins. The enzyme is excreted into the urine where its activity seems to be increased in patients with hypertension and chronic renal failure; it may potentially serve as an indirect index of the renal endothelin system.

Adolescent↗
PubMed1996

Late Proterozoic and Paleozoic Tides, Retreat of the Moon, and Rotation of the Earth

The tidal rhythmites in the Proterozoic Big Cottonwood Formation (Utah, United States), the Neoproterozoic Elatina Formation of the Flinders Range (southern Australia), and the Lower Pennsylvanian Pottsville Formation (Alabama, United States) and Mansfield Formation (Indiana, United States) indicate that the rate of retreat of the lunar orbit is dxi/dt approximately k2 sin(2delta) (where xi is the Earth-moon radius vector, k2 is the tidal Love number, and delta is the tidal lag angle) and that this rate has been approximately constant since the late Precambrian. When the contribution to tidal friction from the sun is taken into account, these data imply that the length of the terrestrial day 900 million years ago was approximately18 hours.

Journal Article↗
PubMed1988

[Quantitative and qualitative studies of Campylobacter in the sewage of a large city].

In a one-year-study wastewater from the sewage system of a big town was examined for the occurrence and distribution of campylobacter spp. The sewage consisted mainly of domestic and industrial wastewater, but also to a small degree of agricultural wastewater and abattoir effluent. Preston broth and agar were used as culture media. The number of campylobacter was determined parallel at 37 degrees C and 42 degrees C by the MPN-method. Three colonies of each agar plate were isolated and biotyped. The number of fecal and total coliforms, pH-value and water temperature were determined as auxiliary parameters. In addition to that meteorological data and data concerning the amount of wastewater flow were available. With exception of the abattoir effluent, which showed higher campylobacter counts, the number of campylobacter in the sewage system generally lay between 10(2) and 10(4) cfu/100 ml. Seasonal variations and influences by the auxiliary parameters could not be ascertained. The biotyping of 2391 campylobacter strains showed a prevalence of Campylobacter coli over Campylobacter jejuni. Campylobacter laridis, fetus and Cephalothin-susceptible Campylobacter coli could be isolated only occasionally. About 20% of the isolated campylobacters were coccoid and not biotypable.

Abattoirs↗
PubMed1998

Long-term follow-up of thromboangiitis obliterans.

BACKGROUND: To date there have been no clinical studies providing data on which to base a long-term medical and social prognosis of thromboangiitis obliterans (TAO). Against this background a retrospective investigation of the longterm course of patients with TAO, who attended the vascular clinic in the medical department of the Klinikum Westend of the Freien Universität Berlin (Free University of Berlin) or the Franziskus Hospital in Berlin was carried out during the period between 1970 and 1990. PATIENTS AND METHODS: The 69 patients making up the overall group included 53 males and 16 females whose average age at the time of initial manifestation of TAO was 34 years. The mean interval between the initial manifestation of the disease and the follow up investigation was 10.7 (range: 2-30) years. The assessment of the course over the long-term was based on a clinical follow-up survey or the data provided by a questionnaire. RESULTS: In 96% of the patients symptoms began in one of the lower limbs, predominantly in the forefoot. During the further course of the illness, 73% of the patients developed symptoms in at least one other limb, either upper or lower. Since the initial development of symptoms, the patients had experienced an average of 5.4 (range: 1-20) acute attacks, that is, episodes of more severe symptoms. The most common reason for hospitalisation was necrosis of the lower limbs, the usual site being the forefoot with primary involvement of the big toe in 57% of the cases. The mean duration of hospitalisation per hospital stay was 36.8 (range: 1-210) days. During the course of the disease 54 (78.2%) of the patients required an average of 3.7 (range: 1-17) operations, 40 (74%) undergoing one or more amputations. Most of the amputations were performed during the first five years after disease onset and the amputation rate was 26%. With the exception of a single lady, all the patients were smokers, and 40 (83.5%) of 48 smokers for whom the relevant information was available persisted with their habit after the onset of the disease. 8 (16.6%) of the 48 patients claimed to have stopped smoking during the course of their disease. Among the patients who continued to smoke, 65% required an amputation, which was almost twice that seen in those who stopped smoking. In terms of number of acute attacks, surgical procedures and smoking, no relationship was found between early age (< 35 years) at onset and progression of the disease. TAO had a pronounced influence on the working life of many of the patients. Twelve changed their jobs because of thromboangiitis obliterans, while 24 (34.8%) retired prematurely on a pension at the mean age of 42. CONCLUSION: The long-term investigation shows that TAO is associated with frequent hospitalisations and surgical procedures. Continued consumption of tobacco in particular was found to be associated with a multiplication of the amputation rate. An influence of patient age at disease onset on the progression of TAO was excluded. In 49 (71%) of the patients, the disease resulted in termination of the working life by either dismissal or premature retirement.

Adolescent↗
PubMed2006

Small molecules, big players: the National Cancer Institute's Initiative for Chemical Genetics.

In 2002, the National Cancer Institute created the Initiative for Chemical Genetics (ICG), to enable public research using small molecules to accelerate the discovery of cancer-relevant small-molecule probes. The ICG is a public-access research facility consisting of a tightly integrated team of synthetic and analytical chemists, assay developers, high-throughput screening and automation engineers, computational scientists, and software developers. The ICG seeks to facilitate the cross-fertilization of synthetic chemistry and cancer biology by creating a research environment in which new scientific collaborations are possible. To date, the ICG has interacted with 76 biology laboratories from 39 institutions and more than a dozen organic synthetic chemistry laboratories around the country and in Canada. All chemistry and screening data are deposited into the ChemBank web site (http://chembank.broad.harvard.edu/) and are available to the entire research community within a year of generation. ChemBank is both a data repository and a data analysis environment, facilitating the exploration of chemical and biological information across many different assays and small molecules. This report outlines how the ICG functions, how researchers can take advantage of its screening, chemistry and informatic capabilities, and provides a brief summary of some of the many important research findings.

Antineoplastic Agents↗
PubMed2004

[Methodological basics of prognosticating the life expectancy of population in big cities].

The reasons of high mortality and of low life expectancy among Russian citizens as well as their sharp fluctuations observed in the 90-ies were explained differently by researchers, however, no attempt was made to analyze the impact made by a huge inflow of immigrant from the republics of the former USSR and "close abroad" in any case studies. In this paper we point at the fact that the mortality statistics and life expectancy in Moscow were influenced, at least for as long as 12 years, by a systemic error, which made the mortality index higher and the life expectancy lower, among Muscovites, due to overestimates of the absolute number of died Muscovites and to underestimates of the city residents. The 2001 life expectancy of men and women in Moscow calculated on the basis of data, from which non-residents who died in the capital were deleted, was 64.7 and 75.0, respectively, but not 61.7 and 73.5 as represented by the official statistics. The maximum negative effect of death cases of non-residents exerted on the life expectancy coincides with the overall mortality peak value in Moscow: life expectancy of Muscovites for 1994 estimated without accounting of the mortality rate for non-residents turned out to be 3.2 years higher for men and 1.5 years higher for women. Supposedly, the Russian mortality statistics is not nation-wide in line with the actual state of affairs. However, the influence of the discussed systemic error in Russia's regions can be expected to be less pronounced since the level of immigration in Moscow is most probably by far higher.

Data Collection↗
PubMed1982

["Multiphase screening" in big industrial city].

Reported in this paper are results obtained from a scheme of computer-backed multiphase screening which has been conducted, with reference to a programme of WHO, for early detection of precursor and early phases of cervical carcinoma and for early detection of patients with hypertension. Evaluation included 54,088 prophylactic examinations through four and a half years. Notifiable diseases of the uterine cervix were recorded from 4.8% of all probands. Among them were 44 cases of severe dysplasia, 156 cases of in situ carcinoma, and 62 cases of invasive cervical carcinoma -- Complementary findings were obtained from 11.8 per cent of the cases. Clinical treatment of patients for such complementary findings were required by more than one in 100 women examined. Another 28 carcinomas were diagnosed and treated, in that context. -- Only 54,020 data were evaluated, in the context of the hypertension screening programme. Hypertension, originally unknown in more than 50 per cent of all cases, was recorded from 19.4 per cent of these women. At total of 16,714 women (42.2 per cent), aged between 20 and 49 years, was on hormonal contraceptives, and hypertension had grown manifest in 12.2 per cent of these.

Adult↗
PubMed2000

Astronomical constraints on the cosmic evolution of the fine structure constant and possible quantum dimensions.

We present measurements of absorption by the 21 cm hyperfine transition of neutral hydrogen toward radio sources at substantial look-back times. These data are used in combination with observations of rotational transitions of common interstellar molecules to set limits on the evolution of the fine structure constant: alpha/ alpha<3.5x10(-15) yr(-1), to a look-back time of 4.8 Gyr. In the context of string theory, the limit on the secular evolution of the scale factor of the compact dimensions, R, is &Rdot/ R<10(-15) yr(-1). Including terrestrial and other astronomical measurements places 2sigma limits on slow oscillations of R from the present to the epoch of cosmic nucleosynthesis, just seconds after the big bang, of DeltaR /R<10(-5).

Journal Article↗
PubMed2003

Comparative sequences of canine and feline endothelin-1.

BACKGROUND: Endothelin-1 (ET-1, "mature ET-1") is a potent vasoconstrictor peptide that is made along with "big ET-1" from its precursor, preproET-1. Increased plasma concentrations of ET-1 and big ET-1 occur with various forms of cardiovascular disease in humans. Our laboratory is investigating plasma endothelins as diagnostic tests of cardiovascular disease in dogs and cats; however, commercial immunoassays designed specifically for use in dogs and cats are limited. OBJECTIVE: Amino acid sequences of feline and canine big ET-1 were obtained and used to predict antibody cross-reactivity with immunoassay test kits from other species. METHODS: Genomic DNA was extracted from peripheral blood and total RNA was extracted from canine and feline left ventricles for reverse transcription polymerase chain reaction (PCR) and PCR amplification of segments of the canine and feline preprohormone containing the big ET-1 sequences. The derived amino acid sequences were compared with known big ET-1 and ET-1 sequences of several other species, including human, mouse, and rat. RESULTS: Feline and canine big ET-1 had 87-97% and 89-100% homology, respectively, with that of other mammalian species. Canine ET-1 was identical to human, mouse, and rat ET-1. In contrast, the amino acid sequence of feline ET-1 was unique owing to a leucine for methionine substitution at position 7. CONCLUSIONS: It is highly likely that anti-human and anti-rodent ET-1 antibodies will cross-react with mature canine ET-1. In contrast, antibodies to mature ET-1 intended for use with feline tissues and antibodies to big ET-1 in either dogs or cats may have partial or no cross-reactivity depending on the peptide sequences used to produce the antibodies.

Amino Acid Sequence↗
PubMed2001

Distinct cellular localization and regulation of endothelin-1 and endothelin-converting enzyme-1 expression in the bovine corpus luteum: implications for luteolysis.

Endothelin-1 (ET)-1 within the corpus luteum (CL) is rapidly up-regulated during natural or PGF(2 alpha)-induced luteolysis; however, such an increase was not observed at early luteal stage, when the CL is refractory to PGF(2 alpha). The mature and active form of ET-1 is derived from the inactive intermediate peptide, big ET-1, by ET-converting enzyme (ECE)-1. This study therefore examined the developmental and cell-specific expression of ECE-1 in bovine CL. A significant, 4-fold, elevation in ECE-1 expression (mRNA and protein levels) occurred during the transition of the CL from early to midluteal phase. Analysis using in-situ hybridization and enriched luteal cell subpopulations showed that both steroidogenic and endothelial cells of the CL expressed high levels of ECE-1 mRNA; prepro ET-1 mRNA, on the other hand, was only expressed by resident endothelial cells. These data suggest that luteal parenchymal and endothelial cells may cooperate in the biosynthesis of mature bioactive ET-1. In the mature CL, ECE-1 mRNA increase occurred both in steroidogenic and endothelial cells and was accompanied by a significant rise in ET-1 peptide. However, in contrast to ECE-1, prepro ET-1 mRNA levels were similar in early and midluteal-phase CL. Low ECE-1 levels during the early luteal phase, restricting the production of active ET-1, may explain why the immature CL is able to withstand PGF(2 alpha)-induced luteolysis.

Animals↗
PubMed1998

Diversity of single potassium channels in isolated snail neurons.

Comparison of K+ channels in mollusk and mammalian neurons has been made to elucidate their fundamental properties. Using patch clamp cell-attached configuration, K+ channels in isolated snail neurons were separated into three subtypes: with big (BKC), medium (MKC) and small (SKC) unitary conductances. BKC and MKC were activated at -30 mV and SKC at more negative potentials. BKC and MKC proved sensitive to TEA, whereas SKC were sensitive to 4-AP. Cd2+ in the pipet decreased unitary conductance of BKC by 55% and of MKC by about 31%. Bath application of 5-HT selectively suppressed MKC. It is suggested that BKC can be referred to large conductance Ca(2+)-dependent K+ currents (KCa), MKC to intermediate conductance KCa and SKC channels comply with the characteristics of A current of mammals. These data show that KCa and A currents may be the most general types of currents generated by K+ channels.

Animals↗
PubMed2000

Expression of penile neuronal nitric oxide synthase variants in the rat and mouse penile nerves.

Penile erection is mediated by nitric oxide (NO) synthesized by the neuronal nitric oxide synthase (nNOS). In the rat penis, the main nNOS mRNA variant, PnNOS, differs from cerebellar nNOS (CnNOS) by a 102 base pair insert encoding a 34-amino acid sequence. In the mouse, two nNOS mRNAs have been identified: nNOSalpha, encoding a 155-kDa protein, and an exon 2-deletion variant, nNOSbeta, encoding a 135-kDa protein that lacks a domain where a protein inhibitor of nNOS (PIN) binds. We wished to determine whether PnNOSalpha and beta are expressed in the rat penis and are located in the nerves and whether the beta form persists in the potent nNOS knock-out mouse (nNOS( big up tri, open big up tri, open)). A PnNOS antibody against the insert common to both PnNOSalpha and beta detected the expected 155-kDa protein in PnNOSalpha-transfected cells. This antibody, and the one common to PnNOS/CnNOS, showed (on Western blots) the 155- and 135-kDa nNOS variants in rat penile tissue during development and aging. PnNOSalpha mRNA and its subvariants were found as the main nNOS in the penile corpora, the cavernosal nerve, and the pelvic ganglia, with lower levels of PnNOSbeta mRNA. In tissue sections, PnNOS protein was immunodetected in the penile nerve endings in the rat and in the nNOS wild-type and nNOS( big up tri, open big up tri, open) mice. An antibody against the sequence encoded by exon 2 did not react (on Western blots) with the 135-kDa band, which confirms that this protein is the beta form. In conclusion, both PnNOSalpha and beta are expressed in the rat penis at all ages and are located in the nerves. The beta form may allow nitric oxide synthesis during erection to be partially insensitive to PIN. The residual expression of PnNOS, and possibly CnNOS, in the penis of the nNOS( big up tri, open big up tri, open) mouse occurs through transcription of the beta mRNA, and this may explain the retention of erectile function when the expression of nNOSalpha is disrupted.

Amino Acid Sequence↗