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Biomedical subjects

H Mann

Publications and source records attributed to H Mann.

At least 19 recordsLinked to original sources

Function and subnuclear distribution of Rpp21, a protein subunit of the human ribonucleoprotein ribonuclease P.

Rpp21, a protein subunit of human nuclear ribonuclease P (RNase P) was cloned by virtue of its homology with Rpr2p, an essential subunit of Saccharomyces cerevisiae nuclear RNase P. Rpp21 is encoded by a gene that resides in the class I gene cluster of the major histocompatibility complex, is associated with highly purified RNase P, and binds precursor tRNA. Rpp21 is predominantly localized in the nucleoplasm but is also observed in nucleoli and Cajal bodies when expressed at high levels. Intron retention and splice-site selection in Rpp21 precursor mRNA regulate the intranuclear distribution of the protein products and their association with the RNase P holoenzyme. Our study reveals that dynamic nuclear structures that include nucleoli, the perinucleolar compartment and Cajal bodies are all involved in the production and assembly of human RNase P.

3T3 Cells↗

Pathological excretion patterns of urinary proteins in miners highly exposed to dinitrotoluene.

A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins alpha 1-microglobulin and glutathione-S-transferase alpha (GST alpha) as biomarkers for damage of the proximal tubule and glutathione-S-transferase pi (GST pi) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers alpha 1-microglobulin, GST alpha, and GST pi consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.

Biomarkers↗

Perinatal risk for mortality and mental retardation associated with maternal urinary-tract infections.

OBJECTIVE: The researchers analyzed the relationship between fetal exposure to maternal urinary tract infections (UTIs) and mental retardation or developmental delay and fetal death. STUDY DESIGN: A retrospective cohort design was used to explore the risk for fetal death and mental retardation or developmental delay associated with exposure to maternal UTI during pregnancy. POPULATION: Matched maternal-child pairs from the National Collaborative Perinatal Project (NCPP) from the decades of 1960 and 1970 were compared with a previous analysis of the South Carolina Medicaid Reimbursement System (Medicaid) for 1995-1996. Both data sets are representative of poor women and their children. OUTCOMES MEASURED: The outcomes measured were fetal death and mental retardation or developmental delay in the live-born children. RESULTS: There was an increased relative risk (RR) for mental retardation or developmental delay in the third trimester of pregnancy (RR=1.40; 95% confidence interval [CI], 1.01-1.95) in the NCPP, and there was a similar risk in the Medicaid data. The third trimester relative hazard for fetal death associated with maternal UTI was 2.23 (95% CI, 1.40-3.55). CONCLUSIONS: The findings support an association between maternal UTI and fetal death and mental retardation or developmental delay. These results confirm the importance of diligent diagnosis and treatment of maternal UTI by prenatal care providers.

Adolescent↗

Urinary tract infections during pregnancy in South Carolina.

This study presents evidence that over 20 percent of pregnant women with a UTI in South Carolina did not have an antibiotic pharmacy claim within 14 days of diagnosis. Untreated maternal UTI in pregnancy was associated with a 22 percent increased risk for MR/DD in the infant compared to the risk for women who had a UTI and a pharmacy claim for an antibiotic and 31 percent increased risk compared to women who did not have a UTI. The importance of medications compliance should be emphasized in the care of pregnant women.

Anti-Infective Agents, Urinary↗

Influence of recombinant human erythropoietin therapy on plasma endothelin-1 levels during hemodialysis.

The correction of anemia with human recombinant erythropoietin (rHuEPO) in end stage renal disease is associated with hypertension in about one third of hemodialysis patients. The pathogenesis of the rHuEPO-induced hypertension is still uncertain, though evidence of the involvement of endothelial cells has emerged. The aim of this study was to determine plasma endothelin-1 during hemodialysis and to compare the endothelin-1 levels in hemodialysis patients with and without rHuEPO substitution. Nineteen stable patients (13 male and 6 female, mean age 62 +/- 11 years) with end stage renal disease were studied. Cuprophan dialysers (GFS 12, Gambro, Lund, Sweden) were used for hemodialysis in all cases. rHuEPO (40 U/kg s.c.) was administered to 10 patients. Blood pressure (BP; RR mmHg) and blood volume changes (deltaBV; hemoglobinometry %) were serially measured. Samples were taken before and every hour during hemodialysis. Plasma endothelin-1 was measured by ELISA (R&D Systems, Minneapolis, USA) and corrected for hemoconcentration. Endothelin-1 concentration was elevated before commencement of hemodialysis (1.16 +/- 0.36 pg/ml) when compared to healthy controls (ref. 0.3-0.9) and increased to 1.47 +/- 0.51 pg/ml by the end of the session (p<0.05). In patients under rHuEPO-substitution plasma endothelin-1 was higher when compared to patients without substitution before (1.25 +/- 0.3 vs. 1.05 +/- 0.3 pg/ml) and at the end of HD (1.62 +/- 0.5 vs. 1.28 +/- 0.3 pg/ml, p<0.05). There was no difference in BP and deltaBV between the two groups during treatment. Plasma endothelin-1 was higher in hemodialysis patients and there was a continuous rise in plasma endothelin-1 during a session. Comparison of two groups of hemodialysis patients with and without s.c. rHuEPO-replacement treatment revealed a significantly higher plasma endothelin-1 concentration in patients with s.c. rHuEPO treatment. However, the elevated endothelin-1 levels were not accompanied by arterial hypertension.

Anemia↗

Urinary tract infections during pregnancy and mental retardation and developmental delay.

OBJECTIVE: To investigate the association between urinary tract infections during pregnancy and mental retardation or developmental delay in infants. METHODS: An inception cohort design was used to analyze Medicaid maternal and infant-linked records and vital records for 41,090 pregnancies from 1995-1998. RESULTS: The relative risk (RR) for mental retardation or developmental delay among infants of mothers with diagnosed urinary tract infections but no antibiotic claims was 1.31 with a 95% confidence interval (CI) of 1. 12, 1.54 compared with the group without urinary tract infections. The RR for infants of mothers with urinary tract infections without antibiotic claims was 1.22 (95% CI 1.02, 1.46) compared with infants of mothers with urinary tract infections and antibiotic claims. The RR was significant in the first trimester (1.46, 95% CI 1.07, 1.99) and third trimester (1.41, 95% CI 1.11, 1.79) after controlling for race and gestational age at birth. CONCLUSION: There was a statistically significant association between maternal urinary tract infections without evidence of antibiotics and mental retardation or developmental delay in infants. The relationship persisted when we assumed that over 30% of women who had antibiotic claims filled but did not take the medicine, and 40% of the women who did not have antibiotic claims did take the medication.

Adolescent↗

Parental perception of the quality of life among children with epilepsy or diabetes with a new assessment questionnaire.

This paper describes the evaluation of a newly designed questionnaire to assess the quality of life among children with epilepsy or diabetes. Factor analysis identified one factor, the impact on the parents and the family, which was responsible for over a third of the variance in the two illness groups. Two other factors, impact on development and impact on health, were also found in the epilepsy group. The questionnaire discriminates well between children with epilepsy or diabetes, showing that the former is more affected than the latter. Children with more severe epilepsy are seen by parents to have a worse quality of life than children whose epilepsy is well controlled.

Chi-Square Distribution↗

Sodium modeling.

The most serious side effects induced by hemodialysis therapy are caused by changes in sodium concentration and subsequent water shift between the intracellular and extracellular fluid compartment. Because of inadequate precision of proportioning, a certain sodium concentration and considerable error in the measurement of sodium concentration in dialysis fluid and plasma water, an error of up to 10 g in the diffusive exchange of sodium chloride remains in most dialysis sessions. Common side effects occur within this sodium balance error. Sodium modeling is a simplified mathematical method to describe quantitatively the fluid exchange in the body caused by changes in extracellular sodium concentration. It is based on fundamental physiologic properties of sodium and its permeability through the corresponding membranes. It also explains the different working mechanisms of sodium- and urea-related changes in osmolarity. Sodium modeling is a helpful tool for the illustration of the effects of changes in sodium concentration and ultrafiltration rate on sodium balance during one dialysis session. Sodium profiling is a method employed to avoid unwanted side effects of hemodialysis therapy by deliberately changing the sodium concentration in dialysis fluid during the course of a dialysis session. Clinical reports on practicing sodium profiling are unsatisfactory, involving only short trial periods in most cases. Most of the studies reported positive sodium balance with temporary decreases in intradialytic hypotension and less blood volume reduction, but with increases in thirst and body weight. To date, no validated studies with suitable control of sodium balance have been published that clearly demonstrate the long-term benefits of this mode of therapy compared with the use of constant dialysate sodium concentrations.

Humans↗

Importance of sodium dodecyl sulfate pore-graduated polyacrylamide gel electrophoresis in the differential diagnostic of Balkan nephropathy.

Balkan nephropathy (BN) is an endemic disease, which leads to end-stage renal failure and artificial renal replacement therapy. Pathologically it is characterized by progressive interstitial nephritis in a large population of villages situated in the proximity of a bend of the Danube up to a distance of 100 km from the river in several parts of Bulgaria, Romania, and the former Yugoslavia. The urinary proteins of 19 patients with BN from the region of Vratza, Bulgaria were examined using ultrathin layer sodium dodecyl sulfate (SDS) pore-graduated polyacrylamide gel electrophoresis (PAGE) and silver staining. The documentation of urinary proteins pattern was performed using laser densitometry and consecutive electronic processing for the purpose of characterizing and quantifying protein excretion. Our results show that the proteinuria of BN is predominantly tubular, consisting of low molecular weight species (10-65 kilodaltons). The amount of tubular protein changes with the progression of the disease. SDS-polyacrylamide gel electrophoresis (PAGE) is a diagnostic method for early diagnosis of tubular failure in BN. Using our method of SDS-PAGE, tubular failure can be detected even at a total protein concentration below 0.1 g/L and when the serum creatinine concentration is normal. Additionally, our method of SDS-PAGE supports the differentiation of BN from glomerular disease.

Aged↗

Pathological excretion patterns of urinary proteins in renal cell cancer patients exposed to trichloroethylene.

A study was carried out to investigate urinary protein excretion patterns by means of SDS-polyacrylamide-gel-electrophoresis (SDS-PAGE) in renal cell cancer patients who had previously been exposed to high levels of trichloroethylene. Thirty-eight out of 41 (93%) renal cell cancer patients investigated had former extensive trichloroethylene exposure, but only 23 out of 50 (46%) renal cell cancer patients without a history of occupational exposure to trichloroethylene revealed urinary protein patterns indicative of toxic effects on the tubular system. One hundred controls without histories of overt renal disease and not occupationally exposed to trichloroethylene were examined in the same way; only 11 (11%) of them displayed protein excretion patterns indicative of damage to the renal tubule. These results are supported by alpha 1-microglobulin excretion data. The following conclusions are drawn: (1) Substantially more cases of tubular damage are found amongst renal cell carcinoma patients having been exposed to substantial levels of trichloroethylene over many years as compared with renal cell carcinoma patients not exposed to trichloroethylene. (2) The results support the view that chronic tubular damage is a precondition for the nephrocarcinogenic effect of trichloroethylene. (3) The findings indicate that urine protein patterns, on the basis of the SDS-PAGE methodology, represent a 'biological effect parameter' for the medical surveillance of persons occupationally exposed to trichloroethylene.

Aged↗

Dialysis and pregnancy--a case report and review of the literature.

We report on a patient with an eight-year history on maintenance hemodialysis treatment without residual renal function in whom pregnancy was successfully managed through to the 29th week. During this time, under carefully modified dialysis treatment, the nephrologic course, as well as materno-fetal flow relationships were unremarkable. Fetal development was appropriate for gestational age. However, pregnancy was complicated by polyhydramnios, which necessitated i.v. tocolysis. In the 28 + 6th week of gestation, cesarean section was performed because of an antibiotic-resistant fever of unclear origin which ceased within two days of delivery. Although the postnatal course of the adequately developed baby was complicated by the respiratory distress syndrome, normal development continued. We emphasize that the intensive interdisciplinary cooperation of nephrologists and obstetricians is imperative for the successful management of pregnancy under these conditions. In these pregnancies, the main fetal problems consist of premature labor because of polyhydramnios, preterm delivery, intrauterine growth retardation and stillbirth. The mother is threatened by the development of superimposed pre-eclampsia, left ventricular failure because of volume overload and progressive anemia. In order to maintain a well-balanced homeostasis, intensification of dialysis therapy by an increase in frequency and duration is the most important therapeutic approach. Accurate fetal monitoring including frequent examination of the feto-maternal circulation by Doppler sonography as well as attentive surveillance of the mother is required to recognize the above mentioned complications.

Adult↗

Isolation and structural characterization of five oligosaccharide alpha1-phosphates and one sulfated glycopeptide from hemofiltrate.

Five oligosaccharide alpha1-phosphates and one sulfated glycopeptide have been isolated from the hemofiltrate of one patient with end-stage renal disease. Isolation of these compounds has been achieved using reverse osmosis, ion-exchange and size-exclusion chromatography and high performance liquid chromatography. The structures were predominantly elucidated by one- and two-dimensional 1H and 31P NMR spectroscopy. The chemical structures were determined to be: 1 NeuAc alpha2-3Gal alpha1-OPO3H2; 2 NeuAc alpha2-6Galbeta1-4GlcNAc alpha1-OPO3H2; 3 NeuAc alpha2-3Galbeta1-3GalNAc alpha1-OPO3H2; 4 NeuAc alpha2-3Galbeta1-3[NeuAc alpha2-6]GalNAc alpha1-OPO3H2 (proposed structure); 5 Fuc alpha1-2Galbeta1-4[Fuc alpha1-3]GlcNAc alpha1-OPO3H2; 6 HOSO3-4Fuc alpha1-6GlcNAcbeta1-NAsn. While 2 and 3 have been previously characterized as compounds of urine and hemofiltrate, the oligosaccharide alpha1-phosphates 1, 4, and 5 could be isolated--to our knowledge--for the first time from biological material. Compound 6 is the first glycopeptide reported to contain a 4-sulfated fucose residue.

Female↗

Uteroplacental and fetoplacental blood flow in a patient with renal anemia.

We report on Doppler sonographic findings of a dialysis patient with renal anemia during otherwise uncomplicated pregnancy. Uteroplacental and fetoplacental flow relationships before, as well as after the dialysis treatments during the course of the pregnancy were in the normal range. The favorable flow condition in the utero- and fetoplacental circulation was associated with a low hematocrit. This in accordance with previous reports indicates a more favorable maternal and fetal outcome in association with a low hematocrit/hemoglobin concentration.

Adult↗

Overexpression of superoxide dismutase and catalase in immortalized neural cells: toxic effects of hydrogen peroxide.

Hydrogen peroxide (H2O2) is a known toxicant which causes its damage via the production of hydroxyl radicals. It has been reported to cause both necrotic and apoptotic cell death. The present study was undertaken to evaluate the mode of H2O2-induced cell death and to assess if overexpression of catalase could protect against its toxicity. H2O2 causes cell death of immortalized CSM 14.1 neural cells in a dose-dependent manner. H2O2-induced death was associated with DNA laddering as shown by agarose gel electrophoresis. Stable overexpression of catalase by transfection of a vector containing human cDNA into these cells markedly attenuated H2O2-induced toxic effects. Transfection of a vector containing a SOD cDNA afforded no protection. These results indicate that H2O2 can lead to the activation of endonuclease enzyme that breaks DNA into oligosomes. These cells which overexpress catalase or SOD will help to determine the specific role of H2O2 or O2- in the deleterious effects of a number of toxins.

Catalase↗

Differential toxic effects of methamphetamine (METH) and methylenedioxymethamphetamine (MDMA) in multidrug-resistant (mdr1a) knockout mice.

The toxic effects of methamphetamine (METH) (2.5, 5.0 and 10.0 mg/kg) and methylenedioxymethamphetamine (MDMA) (5.0, 10.0 and 20.0 mg/kg) on dopaminergic systems were assessed in the striatum and of the nucleus accumbens in mdr1a wild-type and knockout mice. METH caused significant dose-dependent decreases of dopamine (DA) and DA transporters (DAT) in the striatum and the nucleus accumbens (NAc) of both wild-type and knockout mice. The lowest doses of METH (2.5 mg/kg) caused only small changes in the wild-type, but marked. decreases in the mdr1a knockout mice. The two higher doses (5 mg/kg and 10 mg/kg) caused similar changes in both strains of mice. In contrast to METH, MDMA caused greater percentage decreases in DAT in the wild-type mice. For example, the lowest dose (5 mg/kg) caused significant decreases in DAT in the NAc of wild-type but not of mdr1a knockout mice. The highest dose (20 mg/kg) caused similar changes in both the strains. These results suggest that METH and MDMA interact differentially with P-glycoproteins. These observations document, for the first time, a role for these proteins in the entry of METH and MDMA into the brain via the blood-brain barrier, with P-glycoprotein possibly facilitating the entry of MDMA but interfering with that of METH into the brain.

Animals↗

Ten-year follow-up results from the Goettingen Risk, Incidence and Prevalence Study (GRIPS). I. Risk factors for myocardial infarction in a cohort of 5790 men.

Besides the accepted major risk factors for myocardial infarction (MI), cholesterol, hypertension and smoking, several other variables such as lipoproteins, apolipoproteins, fibrinogen and family history of MI, have been considered, but their usefulness as predictors of MI is controversially discussed. The Göttingen Risk Incidence and Prevalence Study (GRIPS) aimed to evaluate the independent impact of the latter in comparison to the established risk factors. GRIPS is a prospective cohort study, which included 5790 men, aged 40-59.9 years, without cardiovascular disease at baseline. Multivariate logistic regression models for the estimation of the MI risk based on the 10-year follow-up data from 97.4% of the study participants established LDL cholesterol as the strongest predictor of MI. It was followed by family history of MI, Lp(a), age, smoking, systolic blood pressure, HDL cholesterol (inversely related) and plasma glucose (P < 0.001). Apolipoprotein B as well as the ratios total/HDL cholesterol, LDL/HDL cholesterol and Apo B/AI were less effective predictors than LDL cholesterol and did not contribute independently to the estimation of MI risk. Similarly apoprotein AI was a weaker predictor of MI risk then HDL cholesterol. GRIPS is the first prospective cohort study which clearly justifies the key role of LDL cholesterol in preventive strategies. However, the data also give strong support for the additional consideration of other risk factors for a valid estimation of the MI risk for an individual subject.

Blood Glucose↗