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L Fischer

Publications and source records attributed to L Fischer.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1993

Chiral separation using molecularly imprinted heteroaromatic polymers.

Novel molecularly imprinted polymer systems utilizing 4-vinylpyridine and 1-vinylimidazole as functional monomers have been developed for enantioselective recognition of carboxylic and N-protected amino acids. Non-covalent interactions between the functional monomers and the template molecules were the source of the subsequent recognition sites in the resultant polymers. The capacity of the polymers for molecular recognition was investigated by using them as stationary phases in the HPLC mode. Polymers prepared with 4-vinylpyridine were found to be more efficient in racemic resolution than those prepared with 1-vinylimidazole. When applying a racemic mixture of the template molecule, the polymers showed highest affinity for the enantiomer used as template. Imprints of a racemic template molecule, as expected, did not exhibit enantioselectivity. The optimal molar ratio of 4-vinylpyridine to the template Cbz-L-Asp-OH in the polymerization mixture was determined to be 12:1. In addition to enantioselectivity, the investigated polymers demonstrated 'ligand selectivity', e.g., a Cbz-L-Asp-OH-imprinted polymer was able to separate Cbz-D,L-Asp-OH, but was unable to separate Cbz-D,L-Glu-OH.

Chromatography, High Pressure Liquid↗
PubMed1993

Antigenemia, immunoblotting, and enzyme immunoassay for early diagnosis of cytomegalovirus infection in renal transplant patients.

Timely and rapid diagnosis of cytomegalovirus (CMV) infection is important for the management of transplant patients. We compared three serological assays, IgM immunoblot and IgG/IgM enzyme immunoassay (EIA), as well as the detection of CMV antigens in polymorphonuclear blood leukocytes (antigenemia), for their value in the early diagnosis of CMV infection. Thirty-one patients were monitored longitudinally for 3 months after renal transplantation. Laboratory documented CMV infection occurred in 20 patients. All of these cases showed a positive IgM immunoblot result that was confirmed by at least one of the other test assays (IgG EIA 19/20, antigenemia assay 13/20, and IgM EIA 12/20). All of the ten patients whose clinical picture was compatible with symptomatic CMV disease were positive for CMV infection according to IgM immunoblot and IgG EIA, nine were positive according to the antigenemia assay, and seven were positive according to IgM EIA. With reference to the temporal pattern, the antigenemia assay indicated CMV infection significantly earlier than the serological tests (P < or = 0.05). In symptomatic patients CMV antigen-positive leukocytes were, on the average, detected on the day of onset of symptoms, whereas detection by IgM immunoblot, IgG EIA, and IgM EIA followed 8, 13, and 14 days later, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1993

Cognitive impairment and the use of health services in an elderly rural population: the MoVIES project. Monongahela Valley Independent Elders Survey.

OBJECTIVE: To describe the patterns of use of health and human services by elderly rural individuals and to determine whether cognitively impaired persons had a distinctive pattern of service utilization. DESIGN: An epidemiological survey and cognitive screening of an age-stratified random community sample. SETTING: The mid-Monongahela Valley, a rural community in Southwestern Pennsylvania. PARTICIPANTS: 1366 non-institutionalized persons aged 65 years and older, fluent in English, and with at least a sixth grade education. MEASUREMENTS: We administered a battery of cognitive screening tests (the Mini-Mental State Examination; Immediate and Delayed Recall of a Story; Immediate and Delayed Recall of a Word List; CERAD modification of the Boston Naming Test; Verbal Fluency for initial letters P and S and for names of Fruits and Animals; Temporal Orientation; Praxis; Clock Drawing; and Trailmaking Tests A and B.) We also obtained basic demographic information and inquired about the use of health and human services in the previous year. RESULTS: Approximately 10% of the sample was classified (by operational criteria) as cognitively impaired. In univariate analyses, cognitive impairment was found to be significantly associated with the use of certain health services: hospitalization in the previous 6 months (odds ratio, OR = 2.1; 95% CI = 1.3, 3.3), previous nursing home use (OR = 9.3; 95% CI = 3.8, 22.9), home health care (OR = 4.6; 95% CI = 2.7, 8.0), social services (OR = 6.5; 95% CI = 3.4, 12.4), mental health services (OR = 2.8; 95% CI = 1.2, 6.2), and the regular use of prescription medications (OR = 2.0; 95% CI = 1.3, 3.2). Visits to physicians were not significantly different between the impaired and unimpaired groups. In a multiple regression model, which included age and educational level, the use of home health care (OR = 3.4; 95% CI = 1.8, 6.4) and social services (OR = 2.3; 95% CI = 1.1, 4.9) remained significantly associated with cognitive impairment. CONCLUSIONS: The association of cognitive impairment with the use of these health and human services underscores the general frailty of the impaired group. These findings also point to potential target groups in the community for further evaluation and services for dementia. The findings support the need for education regarding cognitive impairment and dementia to be made available to providers of these services, particularly informal social services such as those provided by church groups.

Aged↗
PubMed1993

Prognostic significance of a formalin-resistant nuclear proliferation antigen in mammary carcinomas as determined by the monoclonal antibody Ki-S1.

Proliferative activity is a potential prognostic indicator of neoplastic cell growth. Usually the assessment of the tumor growth fraction requires specially processed or frozen tissue. We have raised a monoclonal antibody, Ki-S1, suitable for the detection of proliferating cells in routinely processed and paraffin-embedded tissue specimens. A retrospective study was conducted on 83 mammary carcinoma patients with a median follow-up of 45.6 months. Ki-S1 positivity was significantly (P < 0.0001) correlated with the S-phase fraction. A high proliferative activity of more than 30% of tumor cells being Ki-S1-positive was significantly correlated with recurrence (P < 0.001). Cumulative survival was significantly reduced in the high Ki-S1 expressing subgroup. In a multivariate model including Ki-S1, lymph node metastases, tumor size, and progesterone receptor positivity, independent significant information was provided by Ki-S1. We conclude that in mammary carcinomas, Ki-S1-determined growth fraction represents a significant and independent prognostic predictor.

Adult↗
PubMed1993

Adrenergic and non-adrenergic vasoconstrictor mechanisms in the human nasal mucosa.

The possible occurrence of adrenergic and non-adrenergic vasoconstrictor mechanisms has been studied in human nasal mucosa biopsies. The tissue contractions (reflecting vascular tone variation) in response to exogenous noradrenaline (NA), neuropeptide Y (NPY) and somatostatin (SOM) were measured in vitro. Dose-dependent contraction of the nasal mucosa was observed for the three agents studied and the rank order of their vasoconstrictive potency was NA > SOM > NPY. On a molar basis NPY showed an 80% less potent vasoconstrictive activity than SOM. Pretreatment with the alpha-adrenoceptor antagonist phenoxybenzamine (10(-6) M) almost completely abolished the vasoconstrictive response to NA, whereas the effects of NPY and SOM remained intact. The responses to SOM were significantly reduced after pretreatment with high dose of the competitive SOM-antagonist analog cyclo(7-aminoheptanoyl-PHE-D-TRP-LYS-THR[BZL]). When SOM was administered simultaneously with NA, the contractile response was significantly reduced as compared to the effect of NA alone. In contrast, concomitant administration of NPY and NA potentiated the vasoconstrictive effect of NA. The present data suggest that both adrenergic and non-adrenergic vasoconstrictor mechanisms are present in the human nasal mucosa vascular bed. Furthermore, NPY and SOM may act as modulators of the NA-induced vasoconstrictive effects.

Adult↗
PubMed1992

Cloning of the 62-kilodalton component of basic transcription factor BTF2.

Cloning of the mammalian basic transcription factors serves as a major step in understanding the mechanism of transcription initiation. The 62-kilodalton component (p62) of one of these transcription factors, BTF2 was cloned and overexpressed. A monoclonal antibody to this polypeptide inhibited transcription in vitro. Immunoaffinity experiments demonstrated that the 62-kilodalton component is closely associated with the other polypeptides present in the BTF2 factor. Sequence similarity suggests that BTF2 may be the human counterpart of RNA polymerase II initiation factor b from yeast.

Amino Acid Sequence↗
PubMed1992

Class II (B) general transcription factor (TFIIB) that binds to the template-committed preinitiation complex is different from general transcription factor BTF3.

A class II (B) general transcription factor of 34 kDa has been purified from HeLa cells to apparent homogeneity. This factor appears to be transcription factor IIB (TFIIB), since it binds in vitro to template-committed preinitiation complexes formed between a template containing the TATA box/cap-site elements of the adenovirus type 2 major late promoter (Ad2MLP) and recombinant human or yeast TFIID (previously called BTF1) expressed in Escherichia coli. DNase I footprint studies show an extended pattern of protection of Ad2MLP TATA box/cap-site sequences when TFIIB is bound to template-committed complexes, even though TFIIB does not bind on its own to the template in the absence of TFIID. We also show that TFIIB is different from BTF3 by a number of criteria.

Amino Acid Sequence↗