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Biomedical subjects

L Fischer

Publications and source records attributed to L Fischer.

At least 37 records · Page 2Linked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

[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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

Microvessel density and distribution in ductal carcinoma in situ of the breast.

BACKGROUND: Prior studies have suggested that microvessel density is an important prognostic factor in invasive breast cancer. However, the extent and distribution of microvessels in association with ductal carcinoma in situ (DCIS) have not been well defined. PURPOSE: Our goal was to determine the density and distribution of stromal microvessels in DCIS and to investigate the relationships among microvessel density, histopathologic features, HER2/neu oncogene expression, and tumor proliferation rate. METHODS: Of 61 consecutive cases of DCIS identified from hospital pathology reports, 55 cases were evaluated. Breast biopsy specimens had been preserved in paraffin blocks for each DCIS case. Histologic sections of formalin-fixed, paraffin-embedded tissue were stained with hematoxylin-eosin and immunostained for factor VIII-related antigen, the HER2/neu oncoprotein, and the proliferative-associated antigen detected by the Ki-S1 antibody. Factor VIII-stained sections from each case were independently examined by two pathologists and overall tumor-associated stromal microvessel density was scored semiquantitatively on a 1+ to 3+ scale by each observer. Quantitative microvessel counts of DCIS-associated stromal microvessel density were performed. The presence or absence of a cuff of microvessels in immediate apposition to the basement membrane of involved spaces was also evaluated. RESULTS: A variable number of microvessels were found to be present in a diffuse pattern surrounding spaces involved with DCIS. Semiquantitative microvessel scores were 2+ in the majority of cases (53%); 22% of cases were 1+, and 25% were 3+. Quantitative microvessel counts ranged from 17 to 80 vessels per 100x field (0.45 mm2), with a mean +/- SD of 42.9 +/- 16.6. Comedo-type lesions were significantly (P = .004) more often associated with 3+ microvessel density than non-comedo-type lesions by semiquantitative assessment. As determined by both semiquantitative and quantitative analysis, respectively, the presence of prominent microvessel density was significantly associated with marked stromal desmoplasia (P = .05 and P = .04), HER2/neu expression (P = .03 and P = .0002), and high Ki-S1 proliferation index (P = .05 and P = .01). Vascular cuffing around involved spaces was identified in 21 of the 55 cases (38%) and was not significantly associated with histologic features, HER2/neu expression, or Ki-S1 proliferation index. CONCLUSIONS: DCIS of the breast is characterized by two patterns of stromal microvessels. The first pattern is a diffuse increase in stromal microvessels surrounding involved spaces. This pattern is particularly prominent in comedo-type lesions with marked stromal desmoplasia. The second pattern is microvessel cuffing of involved spaces that is present in only a minority of cases and appears unrelated to histologic features evaluated, including DCIS subtype.

Breast Neoplasms↗
PubMed1994

Living donor for liver transplantation.

Since living related liver transplantation was first performed in 1989, more than 150 cases have been performed worldwide, mostly in the United States and Japan. This paper reports the first series of living related liver transplantation in Europe. Twenty living related liver transplantation surgeries were performed over a 13-mo period, with an overall patient survival of 85%. For patients who underwent elective transplantation (n = 13), the survival rate was 100%. Technical complications included one arterial thrombosis necessitating retransplantation and five bile leaks requiring surgical revision. The technical improvements that permit avoidance of these complications are discussed. A detailed description of the living related liver procurement is given. All procurements yielded grafts of excellent quality. No intraoperative complications occurred, and no reoperations were necessary. No heterologous blood transfusion was needed. In two patients, incisional hernias developed after wound infection. Living related liver transplantation does not absolve the transplant community of efforts to promote cadaveric organ procurement. Nevertheless, living related liver transplantation does have the advantage of a readily available graft of excellent quality, permitting transplantation with optimal timing under elective conditions. Several centers are now preparing living related segmental liver transplants, following the model of our protocol, for three reasons: (a) to obtain superior results compared with cadaveric liver transplantation; (b) to overcome cadaveric organ shortage and further reduce pretransplantation mortality and (c) to provide viable organs in countries where cadaveric organ procurement is not established. When performed by a team experienced in pediatric liver transplantation and in adult liver resection, living related liver transplantation is an excellent modality for the treatment of end-stage liver disease in children.

Adult↗
PubMed1994

Late outcome of bleeding gastric ulcer. Five to eight years' follow-up.

BACKGROUND: 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 with bleeding. METHODS: 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 5-8 years (median, 6.5 years). RESULTS: Recurrent ulcer was seen in 17 patients, repeat haemorrhage being the presenting symptom in 13 of them. The estimated cumulative recurrence rate after 2, 5, and 8 years was 10%, 19% and 33%, respectively. Recurrence rate was unaffected by sex, complicating disease, and non-steroidal anti-inflammatory drugs (NSAIDs) 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 with the expected survival rate of the sex- and age-matched background population (p < 0.01), primarily because of 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.

Aged↗
PubMed1993

An androgen receptor mRNA isoform associated with hormone-induced cell proliferation.

The larynx of male Xenopus laevis undergoes an androgen-driven developmental transformation that enables the adult to produce his complex mate attraction song. During the early postmetamorphic period, androgen directs proliferation and differentiation of laryngeal muscle and cartilage. To explore the cellular and molecular basis of androgen control, we have cloned an androgen receptor cDNA from juvenile larynx. Here we identify two androgen receptor mRNA isoforms, alpha and beta, differing within the A/B, or hypervariable, domain. Northern blot analyses reveal that the beta isoform is transiently expressed during early juvenile stages, whereas the alpha transcript is expressed throughout postmetamorphic life. Using in situ hybridization and [3H]thymidine autoradiography, we examined the expression of androgen receptor mRNA isoforms during androgen-evoked cell proliferation and differentiation. The alpha and beta transcripts are coexpressed in proliferating tissues of the juvenile larynx; in postmitotic differentiated tissues, only the alpha transcript is expressed. Because androgen receptor beta mRNA is specifically expressed during hormone-evoked cell proliferation, we propose that this developmentally regulated mRNA isoform is required for the masculine program of cell addition within the developing vocal organ.

Aging↗
PubMed1993

Amplification of c-myc but not of c-erbB-2 is associated with high proliferative capacity in breast cancer.

Proliferative capacity provides an independent prognostic marker of progression in breast cancer. Little is known about the molecular mechanisms influencing the cell division rate in mammary carcinomas. In order to address this issue, the copy numbers of c-erbB-2 (HER/neu) and c-myc protooncogenes that have been shown to be amplified in aggressive types of cancers were determined in 60 mammary carcinomas and related to the proliferation rate. The proliferative activity was determined by labeling of the proliferation-associated nuclear antigen which is defined by the recently described monoclonal antibody Ki-S1. Approximately one-third of samples under investigation displayed a Ki-S1 labeling index exceeding 30%. In this subgroup, amplification of c-myc was found in 52.6%, whereas in the remaining cases, 26.1% exhibited an enhanced copy number of c-myc (P < 0.025). By contrast, c-erbB-2 amplification was not found to be associated with a higher proliferation index. Except for one case of invasive lobular carcinoma, both protooncogenes exhibited regular copy numbers in the low proliferation subgroup (< 20%; P < 0.03). We conclude from our findings that c-myc amplification may be one of the molecular causes underlying the highly proliferating phenotype of mammary carcinoma, known to be associated with an unfavorable clinical course.

Base Sequence↗