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Biomedical subjects

R Schumacher

Publications and source records attributed to R Schumacher.

At least 19 recordsLinked to original sources
PubMed1998

A region of the cellobiohydrolase I promoter from the filamentous fungus Trichoderma reesei mediates glucose repression in Saccharomyces cerevisiae, dependent on mitochondrial activity.

The upstream activating region that controls cellulose-induced expression of the glucose-repressible cellobiohydrolase I gene (UARcb1) of the filamentous fungus Trichoderma reesei is shown to mediate transcription and glucose repression of a reporter gene in Saccharomyces cerevisiae, a unicellular microorganism that lacks the genes required for the utilization of cellulose. Glucose-controlled transcription mediated by UARcb1 requires the products of the genes SNF1 and SSN6, a protein kinase and a repressor, respectively, that regulate glucose-repressible yeast genes. Previously, it has been shown that mitochondrial function is implicated in cellobiohydrolase I gene expression in T. reesei and this sensitivity to the metabolic state of the mitochondria was shown to be transcriptionally controlled by the 5'-flanking sequence of the cbh1 gene [Abrahão-Neto et al. (1995) Biochemistry 34, 10456-10462]. Remarkably, transcription of the reporter gene controlled by UARcb1 in S. cerevisiae also showed a requirement for active mitochondria, suggesting that a common mechanism involving mitochondrial activity controls glucose-repressible genes in both microorganisms.

5' Untranslated Regions↗
PubMed1998

Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions.

Binding proteins for insulin-like growth factors (IGFs) IGF-I and IGF-II, known as IGFBPs, control the distribution, function and activity of IGFs in various cell tissues and body fluids. Insulin-like growth factor-binding protein-5 (IGFBP-5) is known to modulate the stimulatory effects of IGFs and is the major IGF-binding protein in bone tissue. We have expressed two N-terminal fragments of IGFBP-5 in Escherichia coli; the first encodes the N-terminal domain of the protein (residues 1-104) and the second, mini-IGFBP-5, comprises residues Ala40 to Ile92. We show that the entire IGFBP-5 protein contains only one high-affinity binding site for IGFs, located in mini-IGFBP-5. The solution structure of mini-IGFBP-5, determined by nuclear magnetic resonance spectroscopy, discloses a rigid, globular structure that consists of a centrally located three-stranded anti-parallel beta-sheet. Its scaffold is stabilized further by two inside packed disulfide bridges. The binding to IGFs, which is in the nanomolar range, involves conserved Leu and Val residues localized in a hydrophobic patch on the surface of the IGFBP-5 protein. Remarkably, the IGF-I receptor binding assays of IGFBP-5 showed that IGFBP-5 inhibits the binding of IGFs to the IGF-I receptor, resulting in reduction of receptor stimulation and autophosphorylation. Compared with the full-length IGFBP-5, the smaller N-terminal fragments were less efficient inhibitors of the IGF-I receptor binding of IGFs.

3T3 Cells↗
PubMed1997

Safety and efficacy of repeated shockwave lithotripsy of gallstones with and without adjuvant bile acid therapy.

BACKGROUND & AIMS: The value of adjuvant bile acid dissolution therapy after extracorporeal shockwave lithotripsy (ESWL) of gallbladder stones is under debate. A double-blind, randomized, multicenter trial was conducted to determine the safety and efficacy of repeated ESWL with and without adjuvant bile acid therapy. METHODS: At five centers, 153 patients with gallstones and good gallbladder emptying were randomized to undergo up to six high-energy lithotripsy sessions combined with ursodeoxycholic acid (UDCA, 750 mg/day; n = 77) or placebo (n = 76). RESULTS: Six months after the initial treatment, 77% of patients with small single stones (< or = 20 mm in diameter), 60% with large single stones (> 20 mm in diameter), and 41% with multiple stones were free of stones. Administration of UDCA had no effect on stone disappearance in the whole study group but tended to improve stone disappearance rates in patients with large single stones and tended to decrease biliary adverse effects in patients with multiple stones. CONCLUSIONS: Repeated high-energy ESWL without adjuvant bile acid therapy represents a safe and effective treatment in patients with small single stones and good gallbladder emptying. In patients with large single stones and multiple stones, adjuvant bile acid therapy may be beneficial.

Adjuvants, Pharmaceutic↗
PubMed1997

[Cooperating with nursing care].

The highest standard, humanity in the care of patients, efficiency and budgetary responsibility are what is expected of the public health service. Outside pressure makes internal coordination more efficient and effective. Restructuring of personnel and non-personnel budgets within the limits of precision budgeting must be possible. In the interest of the overall goal, professional and individual interests must be put aside and subordinated. Coordinated routines within the occupational group and extended operational times of X-ray apparatus, the laboratory and so on must be possible. We should never forget that the patient must be the centre of attention in research, training and medical care.

Budgets↗
PubMed1996

The effect of early discharge and other factors on readmission rates of newborns.

OBJECTIVE: To assess the relationship between early discharge, breast feeding, and other factors on hospital readmission of newborns. DESIGN: Retrospective record review. SETTING: An urban, private community hospital. PATIENTS: All newborns born over a 1-year period who were readmitted to the hospital within the first 3 weeks of life (n=117). The control group consisted of a systematic sampling of newborns born over the same period who were not readmitted (n=147). RESULTS: Early discharge, defined as discharge when younger than 24, 36, or 48 hours of age, does not seem to contribute to readmission. However, newborns whose initial stay was longer than 72 hours were at significantly lower risk for readmission (P=.02, chi(2)). Factors in the initial hospitalization associated with readmission included vaginal delivery and length of stay less than 72 hours (difference, 12 percentage points; 95% confidence interval [CI], 4% to 20%; P=.005), need for performance of a complete blood count (CBC) (difference, 16 percentage points; CI 6% to 26%; P=.002), presence of jaundice (difference, 17 percentage points; CI, 5% to 29% P=.005), and gestational age 37 weeks or less (difference, 10 percentage points; CI, 2% to 18%; P=.02), discharge weight less than 3 kg (difference, 11 percentage points; CI, 0 to 22%; P=.05). However, almost all newborns delivered vaginally were discharged within less than 72 hours, so our ability to comment on the independent effect of delivery mode on readmission is limited. A trend toward significance was noted between breast-feeding and readmission (difference, 9 percentage points; CI, 0% to 18%; P=.07). However, when only vaginal deliveries were considered, this association was statistically significant (difference, 13 percentage points; CI, 4% to 22%; P=.02). A significant association was noted between breast-feeding and jaundice or dehydration. Of babies admitted with jaundice or dehydration, 94% were breast-fed, compared with 67% of babies admitted with neither jaundice nor dehydration (difference, 27 percentage points; CI, 13% to 41%; P<.001). CONCLUSIONS: These findings strongly suggest that early discharge (at younger than 24, 36, or 48 hours of age) from the hospital is not associated with hospital readmission within the first 3 weeks of life. Factors associated with readmission included breast-feeding, vaginal delivery and length of stay less than 72 hours, jaundice or need for a CBC, gestational age of 37 weeks or less, and discharge weight less than 3 kg.

Female↗
PubMed1996

Hepatic and pancreatic effects of polyenoylphosphatidylcholine in rats with alloxan-induced diabetes.

Polyenoylphosphatidylcholine (PPC: 100 or 300 mg kg-1 b.w., by gastric intubation for 30 days) produced a clearcut protection of the liver of rats treated with alloxan (150 mg kg-1 b.w., i.p.). The liver of rats treated with alloxan was characterized by hydropic dystrophy and lymphocytic infiltrations. Treatment with alloxan increased serum gamma-GT and ALAT activities. The liver structure of rats treated with PPC did not differ from the liver of control animals. PPC normalized the biochemical abnormalities caused by the diabetes. The number of pancreatic islets and beta/alpha cell ratio decreased in the diabetic rats. A number of beta-cells in this group did not contain granules. PPC prevented the decrease in the number of islets and the beta/alpha cell ratio in the pancreas of the diabetic rats. The intensity of staining of beta-cell granules in the pancreas of PPC-treated rats had a position intermediate between the control and diabetic groups. Alloxan increased the blood glucose content where treatment with PPC decreased this. The results suggest that PPC acts as a cytoprotector in the liver and pancreas of rats with experimental diabetes induced by alloxan.

Alloxan↗
PubMed1996

Effect of very delayed repair of congenital diaphragmatic hernia on survival and extracorporeal life support use.

BACKGROUND: Since November 1992, operative repair in neonates with congenital diaphragmatic hernia (CDH) at this institution was delayed until respiratory insufficiency had resolved. METHODS: A retrospective analysis was performed (n = 33) comparing delayed repair with our previously reported institutional experience with immediate repair from January 1988 to October 1992 (n = 66). Infants with severe genetic defects or moribund conditions or who were premature were not considered candidates for repair or extracorporeal life support (ECLS), but they were included in the survival analysis. Survival was defined as hospital discharge. Data were compared with an independent t test or Pearson chi-squared test. RESULTS: Mean age at repair was 8.9 +/- 4.5 days (range, 3 to 20 days). Eleven infants in the study group were placed on ECLS (33% versus 68% in the comparison group; p = 0.001). Six of these infants survived (55% versus 58% in the comparison group; p = 0.846). Of these survivors, one patient was repaired while on ECLS, and the remainder underwent repair after decannulation from ECLS. All 20 of the remaining candidates for repair survived without need for ECLS. Overall survival was 79% versus 56% in the comparison group (p = 0.027). CONCLUSIONS: Our current data suggest that very delayed repair of newborns with CDHs is associated with an increase in the overall survival and a decrease in the use of ECLS when compared with previous experience at this institution.

Extracorporeal Membrane Oxygenation↗
PubMed1996

[Extracorporeal shockwave lithotripsy (SWL) of common bile duct calculi without previous endoscopic papillotomy].

In 17 patients (8 men, 9 women; mean age 61.5 years) with problematic bile-duct stones (papilla endoscopically inaccessible, residual bile-duct stones after recent laparoscopic cholecystectomy or age below 25 years) the chances of successful treatment by ESWL without sphincterotomy were examined. In 15 patients with solitary stones measuring up to 14 mm "pulverization-ESWL" produced complete freedom from stones after spontaneous migration of fragments through the intact papilla. Only two patients with two ductal stones measuring up to 15 mm still had residual fragments in the bile duct after treatment. The ideal stone for ESWL without sphincterotomy is thus the solitary bile-duct stone measuring up to 14 mm. Before performing a high-risk sphincterotomy, before re-operation and in young patients one should therefore always examine whether ESWL without sphincterotomy is indicated.

Adolescent↗
PubMed1995

Identification of a regulatory motif in Hsp70 that affects ATPase activity, substrate binding and interaction with HDJ-1.

The Hsp70 family of molecular chaperones has an essential role in the synthesis, folding and translocation of the nascent peptide chain. While the general features of these activities are well documented, less is understood about the regulation of these activities. The ATPase rate is stimulated by non-native proteins, furthermore, interaction with ATP leads to the release of protein substrate concurrent with a conformational change in Hsp70. One interpretation of these data is that the two domains of Hsp70 interact. In the process of mapping the carboxyl-terminal boundary of the substrate binding domain for human Hsp70, we identified a regulatory motif, EEVD, which is conserved at the extreme carboxyl terminus among nearly all cloned cytosolic eukaryotic Hsp70s. Deletion or mutation of EEVD affects the ATPase activity, the ability to interact with substrates, and interferes with the ability of the mutant Hsp70 to interact with HDJ-1 in the refolding of denatured firefly luciferase. Examination of the biophysical properties of the mutant Hsp70s reveals a change in the overall shape and conformation of the protein consistent with reduced interactions between the two domains. These data suggest that the EEVD motif is involved in the intramolecular regulation of Hsp70 function and intermolecular interactions with HDJ-1.

Adenosine Triphosphatases↗
PubMed1995

"Essential" phospholipids versus nicotinic acid in the treatment of patients with type IIb hyperlipoproteinemia and ischemic heart disease.

In patients with moderate, dietary noncorrigible hyperlipoproteinemia type IIb and ischemic heart disease, treatment with nicotinic acid is limited by the side effects of the drug. In 100 patients, 6-month treatment with nicotinic acid (n = 50) or "essential" phospholipids (EPL); Lipostabil, manufacturer: Rhône-Poulenc Rorer) (n = 50) indicated comparable efficacy for both substances: Significant (p < .001) reductions of serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride values were similar in both groups, while nicotinic acid increased high-density lipoprotein (HDL) cholesterol significantly (p < .01) better than Lipostabil. A detailed analysis of ultracentrifugal lipoprotein profiles, hydroperoxide concentrations in LDL, and cholesterol-accepting properties of HDL in a small number of Lipostabil- and nicotinic acid-treated patients revealed favorable shifts in the lipoprotein profile, significant (p < .05) reductions of LDL hydroperoxides, and favorable increases of the most antiatherogenic HDL2b subfraction only in the Lipostabil-treated group. Clinically, both medications reduced the intensity and number of angina pectoris attacks per week (p < .05), but only Lipostabil-treated patients significantly (p < .05) increased their working capacity in the veloergometric test. Since in the nicotinic acid-treated group dropouts (nine patients, eight related to the drug) and side effects [14] exceeded those in the Lipostabil-treated group (two dropouts not related to the drug, no side effects), it is suggested that Lipostabil is a preferable alternative in the treatment of patients with moderate, dietary noncorrigible hyperlipoproteinemia IIb and ischemic heart disease.

Cholesterol, HDL↗
PubMed1995

Double-blind developmental evaluation at 1-year corrected age of 597 premature infants with birth weights from 500 to 1350 grams enrolled in three placebo-controlled trials of prophylactic synthetic surfactant. American Exosurf Neonatal Study Group I.

Infants enrolled in three clinical trials of prophylactic treatment for respiratory distress syndrome with a single dose of synthetic surfactant (Exosurf Neonatal) or air placebo were monitored through 1-year adjusted age. A total of 1046 infants with birth weights from 500 to 1350 gm were enrolled in the three trials; of the 735 infants who survived to 1 year of age, follow-up evaluations were completed for 597 (80%, air placebo group; 82%, synthetic surfactant group). Infants in the air placebo and synthetic surfactant treatment groups had no differences in general health, growth, or nerodevelopmental outcomes or impairments. These follow-up results at 1-year adjusted age for infants who received a single dose of synthetic surfactant indicate that a single dose of synthetic surfactant reduces mortality without increasing the absolute number or proportion of infants with impairments at 1 year of age.

Air↗
PubMed1995

One-year follow-up of 66 premature infants weighing 500 to 699 grams treated with a single dose of synthetic surfactant or air placebo at birth: results of a double-blind trial. American Exosurf Neonatal Study Group I.

In a multicenter, double-blind, placebo-controlled trial that enrolled 215 premature infants with birth weights of 500 to 699 gm, 106 infants were treated prophylactically with a single 5 ml/kg dose of synthetic surfactant and 109 infants were given an equivalent dose of air placebo shortly after birth. In each group, 40 children survived infancy: 36 children in the air placebo group and 30 children in the synthetic surfactant group were available for follow-up. Weight, height, and head circumference measurements were similar for both groups at 1-year adjusted age. Infants who received synthetic surfactant at birth had statistically similar Bayley Scales of Infant Development scores (mental developmental index, 92 vs 83; psychomotor developmental index, 87 vs 82) compared with controls. Mild to moderate impairments in the synthetic surfactant group were 7% versus 29% in the control group; these differences were not statistically significant. The incidence of retinopathy of prematurity, the number of hospital readmissions, the need for surgery after day 28, evidence of chronic lung disease, the need for respiratory support at 1-year adjusted age, and the incidence of allergies were also not different between the two groups. However, the proportion of infants surviving without impairment was modestly higher in the synthetic surfactant group (8%, air placebo group; 23%, synthetic surfactant group). The findings from this small study indicate that infants weighing 500 to 699 gm who receive a single prophylactic dose of synthetic surfactant at birth have neurodevelopmental outcomes at least equivalent to those of infants given air placebo at 1-year follow-up.

Air↗
PubMed1995

[Absorption of di-linoleoylphosphatidylcholine after oral administration].

Essentiale and Lipostabil contain "essential" phospholipids from the soybean, mainly 1,2-dilinoleoyl-phosphatidylcholine (CAS 998-06-1, DLPC) which is considered as the main active ingredient. A single oral dose of d15-DLPC loaded with deuterium 9 times in the choline and 6 times in the linoleic acid of the 1-position was given to volunteers. Sera from 11 blood samples taken within 48 h after application were examined by means of mass spectrometry with regard to d9-choline and d6-linoleic acid in the 1- and 2-position of serum phosphatidylcholines (PC) as well as in the serum triglycerides. d9-choline, i.e. the total of d15-PC and d9-PC, showed maximum values of 5.6% of the total serum PC concentration. Normally, about 1.3% of PC in the human serum is DLPC. Serum 1-linoleoyl-PC was increased by 32-40% after oral application of d15-DLPC. A minor uptake of d6-linoleic acid into the 2-position of serum PC, which is rich in linoleic acid, and into the serum triglycerides was observed with peak values of 2.3% and 6.1%, resp. The uptake of polyunsaturated PC species like DLPC and 1-linoleoyl-PC into the liver after oral application of drugs containing such species in high amounts like "essential" phospholipids with about 50% of DLPC let expect therapeutic effects on membranes into which this special species is incorporated.

Acylation↗
PubMed1995

[Diagnostic value of protected bronchoalveolar lavage in HIV-associated pneumonia].

OBJECTIVE: The concept of the protected bronchoalveolar lavage (PBAL) is to improve the diagnostic yield in bacterial pneumonia by unifying the high sensitivity of bronchoalveolar lavage (BAL) and specificity of the protected specimen brush (PSB). HIV-infected patients have been shown to have a high incidence of bacterial pneumonia as well as bacterial colonisation of the tracheobronchial tree. We therefore studied the value of PBAL in this population. METHODS: During a period of twelve months 40 episodes in 36 patients with symptoms suggestive of pneumonia were investigated retrospectively. In all cases without infiltrates on chest radiograph a CT-scan of the chest was performed. Patients without infiltrates also in CT-scan served as controls. Bronchoscopic investigation included a PSB and a PBAL in the same lung segment most prominently affected. Microbiological workup was performed for bacterial agents, mycobacteria, fungi, viruses and parasites. Quantitative cultures for bacteria were considered significant in case of > or equal to 10(3) cfu/ml in PSB and > or equal to 10(4) cfu/ml in PBAL. RESULTS: 32 episodes in 28 patients were identified as pneumonia. A definite diagnosis could be established in 19/32 (59%) of cases. Bacteria accounted for 10/19 (53%). Pneumocystis carinii for 9/19 (47%) of cases including one case that revealed mixed infection with Streptococcus pneumoniae and Pneumocystis carinii. Another pneumonia was due to Aspergillus fumigatus. The sensitivity for bacterial pneumonia was 44% for PSB and 56% for PBAL, the specificity 100%. The overall diagnostic accuracy was 60% and 68%, respectively. The yield for Pneumocystis carinii was 8/9 (89%). CONCLUSIONS: PBAL as compared to PSB had a superior diagnostic yield for bacterial pneumonia. As PBAL additionally conserved the yield of BAL reported for Pneumocystis carinii, it may represent a rational diagnostic technique for pneumonia in HIV-infected patients.

AIDS-Related Opportunistic Infections↗