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Biomedical subjects

L Fischer

Publications and source records attributed to L Fischer.

At least 73 records · Page 4Linked to original sources

Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB).

The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms in the brain. Dysfunction of the D2 dopamine receptors leads to aberrant substance-seeking behaviors (ethanol, drugs, tobacco, and food) and other related behaviors (pathological gambling, Tourette's disorder, attention-deficit/hyperactivity disorder). This is the first study supporting a strong association between the dopamine D2 receptor Taq A1 allele with schizoid/avoidant behavior (SAB). Additionally, an albeit weaker association between the 480-bp VNTR 10/10 allele of the dopamine transporter (DAT1) gene with SAB was similarly found.

Adult↗

Cloning of the VASP (vasodilator-stimulated phosphoprotein) genes in human and mouse: structure, sequence, and chromosomal localization.

The genes encoding the vasodilator-stimulated phosphoprotein (VASP) in human and mouse were isolated, and major parts were sequenced. In both species the gene is composed of 13 exons with conserved exon-intron positions. The mouse VASP cDNA sequence was deduced from the genomic sequence. The predicted amino acid sequence is 89% identical to the human protein. The high nucleotide sequence homology extends not only over the coding regions but also into the 3'-UTRs, indicating a possible function in mRNA targeting or regulation of translation. Prominent 5' CpG islands including multiple SP1 sites indicate a housekeeping function of VASP. Using cosmid DNA as a probe for fluorescence in situ hybridization, the human VASP gene was assigned to chromosome 19q13.2-q13.3, an extended region with homology to mouse chromosome 7. A sequence overlap of the VASP 5'-region with the telomeric end of a cosmid contig physically links the VASP gene with ERCC1. VASP is located about 92 kb distal to ERCC1 and about 300 kb proximal to the myotonic dystrophy protein kinase gene.

Amino Acid Sequence↗

bcl-1 rearrangement and cyclin D1 protein expression in mantle cell lymphoma.

Centrocytic lymphoma, or mantle cell lymphoma (MCL), is characterized by a chromosomal translocation t(11;14) (q13;q32) involving the bcl-1 locus on chromosome 11. Cyclin D1 is a cell-cycle regulatory protein essential for G1-S transition and has been identified as a potential transforming gene affected by the translocation. In this study, 32 cases of MCL were analysed for the bcl-1 rearrangement and cyclin D1 protein expression. In 17 cases, a rearrangement at the major translocation cluster of bcl-1 could be detected. Twenty-four cases exhibited nuclear cyclin D1 expression that was not detectable in other B-cell lymphomas (n = 40) or in normal B-cells. In nine MCL samples, cyclin D1 was expressed without a detectable bcl-1 rearrangement. The detection of a t(11;14) by means of classical cytogenetics in one of these cases, however, may suggest that this discrepancy could be due to chromosomal breakages outside the typical translocation cluster region. In two cases, a bcl-1 rearrangement was not accompanied by cyclin D1 expression. This study provides further evidence that cyclin D1 is involved in the pathogenesis of MCL and can be exploited as a diagnostic marker in the differential diagnosis of B-cell lymphomas and in the identification of MCL.

Base Sequence↗

Hepatitis B virus genomes of patients with fulminant hepatitis do not share a specific mutation.

The pathogenesis of fulminant hepatitis B virus (HBV) infection is not well understood. The aim of this study was to investigate whether there is an association between specific viral variants and a fulminant disease course. The entire HBV genomes from the serum of eight patients with fulminant HBV infection and one patient with fulminant hepatitis during reinfection after liver transplantation were investigated. After isolation and amplification of viral DNA by polymerase chain reaction (PCR), plus and minus strands were directly sequenced. Sequence data were analyzed by comparative sequence alignments with 35 and 2 complete HBV genome sequences from patients without and with fulminant hepatitis, respectively. Several point mutations were present in all regions of the genomes. Many nucleotide changes had never or rarely been found in the reported HBV isolates from patients without fulminant hepatitis. A distinct mutation present in all genomes was not identified. Clusters of rare and unique mutations were observed in the enhancer II core promoter region. Mutations previously suggested to be associated with fulminant HBV infection were not consistently found. A precore stop codon mutation at nucleotide position 1896 or an A-to-T mutation at nucleotide position 1762 and a G-to-A mutation at nucleotide position 1764 in the core promoter region were present in four and three cases, respectively. Fulminant HBV infection does not appear to be caused by a specific genomic mutation. However, various mutations clustering in the enhancer II core promoter region may contribute to a fulminant disease course.

Adult↗

The immunomodulatory effects of antibiotics: in vitro and ex vivo investigations of 21 substances by means of the lymphocyte transformation test.

Besides their antimicrobial activity antibiotics can modulate immune response. The paper provides original data about in vitro and in vivo influence of antibiotics on lymphocyte transformation test (LTT) and gives a comprehensive overview of literature data. In the study presented here the influence of several antimicrobial substances on unstimulated and PHA-stimulated lymphocyte transformation was investigated. The proliferative response was measured as (3H) thymidine uptake by lymphocytes. For initial screening the lymphocyte transformation test was performed on murine lymphocytes in vitro. As a whole 21 antimicrobial substances were tested including representative substances of the most important main groups. As a second step experiments were done with selected substances on human lymphocytes that had shown a distinct influence on murine cells in vitro. At therapeutic concentrations a pronounced stimulation of murine lymphocyte transformation was caused by carbapenems, aminothiazole cephalosporins and imidazoles. Purine analogs had only suppressive effects. However, the increased (3H) thymidine uptake in murine cells could not be regularly reproduced in human lymphocytes and in ex vivo experiments.

Animals↗

Catalytical potency of beta-glucosidase from the extremophile Pyrococcus furiosus in glucoconjugate synthesis.

The extremely thermostable wild type and recombinant beta-glucosidases, from Pyrococcus furiosus, served as catalysts for the biotransformation of new glucoconjugates at elevated temperatures. In conversion experiments using the transglucosylation approach, the free or immobilized enzyme accepted primary and even tertiary organic alcohols, as well as primary and secondary artificial organosilicon alcohols, as aglycones. Cellobiose served as the glucose donor. The products obtained were purified by liquid chromatography and analyzed. Using beta-glucosidase a wide variety of products were synthesized. Due to the very broad structural diversity of the aglycones linked to the 1-beta-O-D-glucose, this beta-glucosidase seems to be a useful biocatalyst for regio- and stereoselective sugar derivative synthesis.

Biotransformation↗

In situ splitting of cadaveric livers. The ultimate expansion of a limited donor pool.

OBJECTIVE: The authors evaluate the safety, applicability, and effectiveness of a new technique for split-liver transplantation. SUMMARY BACKGROUND DATA: Split-liver transplantation offers an attractive way to increase the donor pool for cadaveric liver transplantation. The application of this concept has been hampered by inferior patient and graft survivals and higher complication rates. Without supportive data, the concern about increasing biliary leakage and poor initial graft function persisted. The authors focused on the causes of these complications by presenting a new technique to eliminate these problems. METHODS: Liver splitting was performed in the heart-beating cadaveric organ donor, using the technique described for procurement of the left lateral lobe of a live donor. A detailed description of the technique is presented. A retrospective review of the first 14 transplantations resulting from 7 in situ splitting procedures was collected. The results were compared with 19 conventional split-liver transplants performed during the same period. RESULTS: Six-month patient and graft survivals after in situ split-liver transplantation were 92.8% and 85.7%, respectively. Biliary complications were absent. Postoperative courses were mostly uneventful and characterized by lower peak transaminase levels compared with standard techniques. Early graft function of extrahepatic organs procured simultaneously was excellent. CONCLUSIONS: In situ split-liver transplantation provides superior results, related mainly to reduction of cold ischemic damage of the grafts and avoidance of biliary complications. In situ split-liver transplantation renders graft reduction alone obsolete and opens a donor pool for adults to receive right lobes safely. It allows for long-distance sharing between pediatric and adult liver transplant units because the procedure abolishes ex situ benching and prolonged ischemia time and provides two anatomically perfect grafts with hemostasis accomplished.

Adult↗

Transplantation of complete and split liver grafts for patients with fulminant hepatic failure.

Fulminant hepatic failure is associated with considerable mortality under conservative management. The aim of this study was to assess applicability and outcome of liver transplantation using cadaveric and living donated grafts in patients with fulminant hepatic failure. 42 patients presenting with fulminant hepatic failure between 1988 and 1995 were retrospectively analyzed. 37 (88%) met the indication criteria for liver transplantation. 22 patients underwent orthotopic liver transplantation, one patient auxiliary orthotopic liver transplantation. Actual survival rate of these patients is 74% alter a mean follow-up of 23 (3-68) months. 38% (14/37) of the patients with an indication for transplantation did not receive a cadaveric graft due to scarcity of cadaveric organs (n = 9), medical contraindications (n = 3) or spontaneous recuperation (n = 2). Only 21% (3/14) of these patients survived. Due to unavailability of a cadaveric organ four patients, six months to 22 years of age, underwent living related liver transplantation as a last possible treatment option. Three of them died from cerebral herniation. It is concluded that transplantation of a cadaveric graft increased survival rate from 21% to 74% in patients with an indication for liver transplantation. Living related liver transplantation as an individual rescue therapy had no favourable outcome.

Adolescent↗

Selection of the living liver donor.

Living related liver transplantation offers several advantages in comparison to transplantation of cadaver organs. To achieve maximal donor safety evaluation, selection criteria and complications of the donor operation were retrospectively analyzed in living donors of segmental liver transplants. Seventy-three liver donor candidates were evaluated between October 1991 and June 1994. The median age of 42 mothers and 31 fathers was 31 years (range, 19-50 years). The median volume of the left lateral liver lobe comprised 230 ml (100-350 ml). Twenty-four of 73 (33%) donor candidates were not accepted for living donation. Rejection was due to unsuitability of the donor's liver as a graft (n = 13) or due to an increased risk for living donation (n = 11). Of 35 living donations performed so far, one was a full left hemihepatectomy and 34 were left lateral segmentectomies. The length of the donor operation was, on average, 4.3 hr. No heterologous blood was needed. Postoperative complications included death due to pulmonary embolism (n = 1), seizure due to a previously undiagnosed ependymoma (n = 1), bile duct injury (n = 1), incisional hernia necessitating late revision (n = 2), and duodenal ulcer (n = 2). Long-term follow-up revealed no persistent complications. Using our standardized protocol, 33% of young, presumably healthy donor candidates were rejected for living donation.

Adult↗

[Non-surgical treatment of bleeding gastric ulcer. A follow-up after 5-8 years].

UNLABELLED: Gastric ulcer haemorrhage is associated with a high immediate mortality, but few data exist on the late prognosis of these patients. The aim of this study was to determine the long-term recurrence rate and late outcome in patients with gastric ulcer complicated by bleeding. In a prospective follow-up study 90 consecutive patients with a bleeding gastric ulcer discharged after non-operative treatment (bleeding controlled by endoscopic electrocoagulation or ceased spontaneously) were followed up once every year for five to eight years (median 6.5 years). Recurrent ulcer was seen in 17 patients, repeat haemorrhage being the presenting symptom in 13. The estimated cumulative recurrence rate after two, five and eight years was 10%, 19% and 33%, respectively. Recurrence rate was unaffected by sex, complicating disease, and NSAID ingestion before and after the index bleeding episode. The recurrence rate of patients with a history of ulcer before the index bleeding episode did not differ from that of patients with no previous ulcer history. A significantly increased risk of recurrence was seen in patients with previous bleed as opposed to patients with previous non-bleeding ulcer (p < 0.05). The cumulative survival rate was significantly reduced compared to the expected survival rate of the sex- and age-matched background population (p < 0.01), primarily due to diseases not related to the ulcer disease. CONCLUSION: Bleeding gastric ulcer is associated with a relatively low long-term recurrence rate, except in a few patients with a history of previous bleeding ulcer, who have an increased risk of recurrence. Patients with bleeding gastric ulcer have an excess mortality not related to the ulcer disease.

Adult↗

Weapon involvement in home invasion crimes.

OBJECTIVE: To study the epidemiology of home invasion crimes and determine the frequency with which firearms are used to resist these crimes. DESIGN: Prospective case series. SETTING: Atlanta, Ga (population 402,877). METHODS: Between June 1 and August 31, 1994; Atlanta Police Department reports were screened to identify every case of unwanted entry into an occupied, single-family dwelling. Cases of sexual assault and incidents that involved cohabitants were excluded. RESULTS: A total of 198 cases were identified during the study interval. Half (99 cases) involved forced entry into the home. The victim and offender were acquainted in one third of cases. A firearm was carried by one or more offenders in 32 cases (17%). Seven offenders (3.5%) carried knives. In 42% of cases, the offender fled without confronting the victim. Victims who avoided confrontation were more likely to lose property but much less likely to be injured than those who were confronted by the offender. Resistance was attempted in 62 cases (31%), but the odds of injury were not significantly affected by the method of resistance. Forty cases (20%) resulted in one or more victims' being injured, including six (3%) who were shot. No one died. Three victims (1.5%) employed a firearm in self-protection. All three escaped injury, but one lost property. CONCLUSION: A minority of home invasion crimes result in injury. Measures that increase the difficulty of forced entry or enhance the likelihood of detection could be useful to prevent these crimes. Although firearms are often kept in the home for protection, they are rarely used for this purpose.

Crime↗

Preparation of enantiomerically pure (R)-(1-hydroxyethyl)dimethyl(phenyl)silane using resting cells of Saccharomyces cerevisiae (DHW-S-3) as biocatalyst.

The prochiral sila-ketone acetyldimethyl(phenyl)silane (1) was reduced enantioselectively into (R)-(1-hydroxyethyl)dimethyl(phenyl)silane [(R)-2] using resting cells of the commercially available yeast Saccharomyces cerevisiae (DHW S-3) as the biocatalyst. The bioconversion was performed on a 2.0-g scale in a 5-1 bioreactor. Starting with a substrate (1) concentration of 0.4 g.l-1, the highest production rate measured for this bioconversion was about 45-55 mumol (R)-2.l-1.min-1. After an incubation time of 1 h, all substrate in the medium had been converted, either biocatalytically reduced to (R)-2 or (probably chemically) converted into dimethyl(phenyl)silanol (Me2PhSiOH). After extraction of the cell-free medium with ethyl acetate/dichloromethane and subsequent purification of the extract by Kugelrohr distillation and chromatography on silica gel (medium-pressure liquid chromatography), 800 mg (yield 40%) of the bioconversion product (R)-2 was isolated. As shown by HPLC studies (cellulose triacetate as the chiral stationary phase) and 1H-nuclear magnetic resonance experiments (after derivatization of the bioconversion product with a chiral auxiliary agent), compound (R)-2 was almost enantiomerically pure (> 99% enantiomeric excess).

Biotechnology↗

24 hour blood pressure control with once-daily versus twice-daily formulations of diltiazem.

The antihypertensive effects of once-daily diltiazem CD over a 24 hour period were compared with twice-daily diltiazem SR in 95 patients with mild to moderate hypertension using ambulatory blood pressure monitoring. This trial was designed as a multicenter, double-blind, parallel-group study. Following a 2 to 4 week placebo run-in period, diltiazem was administered as once-daily CD or twice-daily SR, starting with 180 mg daily and increasing to a maximum of 360 mg daily, to achieve a seated diastolic blood pressure goal of < or = 90 mmHg as measured by cuff between 08:00 and 10:00 in the morning. Following drug titration, patients received a maintenance dose of diltiazem for an additional 6 week follow-up phase. Twenty-four hour ambulatory blood pressure monitoring recordings were obtained at the end of the placebo, titration, and maintenance phases. Both diltiazem CD and diltiazem SR significantly reduced both systolic and diastolic blood pressure over the 24 hour day and maintained a normal circadian pattern. As well, treatment with once-a-day diltiazem CD significantly decreased the slope of the early morning rise of diastolic and mean blood pressure. Thus, diltiazem CD is as effective as diltiazem SR in lowering diastolic blood pressure over a 24 hour period and has the advantage of a once-daily formulation.

Adolescent↗

Purification and characterization of a thermotolerant beta-galactosidase from Thermomyces lanuginosus.

A new inducible intracellular beta-galactosidase (EC 3.2.1.23) of the thermophilic fungus Thermomyces lanuginosus was purified by fractional salt precipitation, hydrophobic interaction, and anion exchange chromatography. The first 22 amino acid residues were determined by N-terminal sequencing. Electrophoretic investigations revealed a dimeric enzyme with a molecular mass of 75 to 80 kDa per identical subunit and an isoelectric point of 4.4 to 4.5. The native beta-galactosidase was identified as a glycoprotein by the enzyme-linked immunosorbent assay technique. The beta-galactosidase activity was optimal at pH 6.7 to 7.2, and the enzyme displayed stability between pH 6 and 9. It was completely stable at pH 6.8 and 47 degrees C for 2 h. After 191 h at 50 degrees C, the remaining beta-galactosidase activity of an enzyme fraction after salt precipitation was 58%. The beta-galactosidase hydrolyzed p- and o-NO2-phenyl-beta-D-galactopyranoside, lactose, lactulose, MeOH-beta-D-galactopyranoside, phenyl-beta-D-galactopyranoside, and p-NO2-phenyl-alpha-L-arabinopyranoside. The kinetic constants (Km) measured for p- and o-NO2-phenyl-beta-D-galactopyranoside and beta-lactose were 4.8, 11.3, and 18.2 mM, respectively.

Amino Acid Sequence↗