Biomedical subjects

J Friedrich

Publications and source records attributed to J Friedrich.

At least 37 records · Page 2Linked to original sources

PubMed2000

ATP synthesis during low-flow ischemia: influence of increased glycolytic substrate.

BACKGROUND: Our goals were to (1) simulate the degree of low-flow ischemia and mixed anaerobic and aerobic metabolism of an acutely infarcting region; (2) define changes in anaerobic glycolysis, oxidative phosphorylation, and the creatine kinase (CK) reaction velocity; and (3) determine whether and how increased glycolytic substrate alters the energetic profile, function, and recovery of the ischemic myocardium in the isolated blood-perfused rat heart. METHODS AND RESULTS: Hearts had 60 minutes of low-flow ischemia (10% of baseline coronary flow) and 30 minutes of reperfusion with either control or high glucose and insulin (G+I) as substrate. In controls, during ischemia, rate-pressure product and oxygen consumption decreased by 84%. CK velocity decreased by 64%; ATP and phosphocreatine (PCr) concentrations decreased by 51% and 63%, respectively; inorganic phosphate (P(i)) concentration increased by 300%; and free [ADP] did not increase. During ischemia, relative to controls, the G+I group had similar CK velocity, oxygen consumption, and tissue acidosis but increased glycolysis, higher [ATP] and [PCr], and lower [P(i)] and therefore had a greater free energy yield from ATP hydrolysis. Ischemic systolic and diastolic function and postischemic recovery were better. CONCLUSIONS: During low-flow ischemia simulating an acute myocardial infarction region, oxidative phosphorylation accounted for 90% of ATP synthesis. The CK velocity fell by 66%, and CK did not completely use available PCr to slow ATP depletion. G+I, by increasing glycolysis, slowed ATP depletion, maintained lower [P(i)], and maintained a higher free energy from ATP hydrolysis. This improved energetic profile resulted in better systolic and diastolic function during ischemia and reperfusion. These results support the clinical use of G+I in acute MI.

Adenosine Triphosphate↗

PubMed2000

[Long-term follow up of bile duct injury by laparoscopic cholecystectomy and reconstruction with jejunum interposition].

The follow-up of patients with severe bile duct lesions after laparoscopic cholecystectomy often shows secondary complications. We report on a female patient suffering from long-lasting complications after bile duct injury and early reconstruction by end-to-end anastomosis via a T-tube drainage. More than 5 years later and after multiple dilatation and stenting of the bile duct stenosis the patient was treated with an expanding metal stent. The severe cholangitis persisted. So the patient was operated on: bile duct and connected stent were resected. The reconstruction was performed with an isoperistaltic jejunal conduit. More than 24 months later the patient is healthy and at work again.

Cholangitis↗

PubMed2000

Keratinase of Doratomyces microsporus.

The fungus Doratomyces microsporus produced an extracellular keratinase during submerged aerobic cultivation in a medium containing a protein inducer for enzyme synthesis. The keratinase was purified to homogeneity using hydrophobic interaction chromatography followed by gel chromatography. The molecular weight was estimated to be 33 kDa (from SDS-PAGE analysis) or 30 kDa (by gel chromatography), suggesting a monomeric structure. The isoelectric point of the enzyme was determined to be around 9. The optimal pH and temperature for keratinolytic activity were pH 8-9 and 50 degrees C, respectively. The serine protease inhibitor PMSF totally inhibited the keratinase. The enzyme was not glycosylated. It was capable of hydrolysing different keratinous materials as well as some non-keratinous proteins. Hydrolysis of some synthetic substrates, specific for known proteinases, suggested that the keratinase of D. microsporus is close to proteinase K.

Animals↗

PubMed1999

A first order experimental design to assess soluble proteins released by a new keratinase from Doratomyces microsporus on human substrates.

The influence of temperature, pH, keratinase concentration, substrate concentration and incubation time on the soluble proteins released by a new keratinase from Doratomyces microsporus was studied with an experimental design assisted by a simplex method. Only 16 spectrophotometric analyses were required. This study was carried out by measuring, according to Smith's method, the concentration of soluble proteins released by the enzyme on two human substrates: stratum corneum and nails. Results give optimum conditions for the keratinase to release the soluble proteins: Temperature, 28 degrees C; pH, 9.5; keratinase concentration, 0.94% (weight of keratinase lyophilisat/final volume), substrate concentration, 4.9% (weight of skin powder/final volume); and a 5 h 50 min incubation for the stratum corneum. Temperature, 37 degrees C; pH, 9.2, keratinase concentration, 0.11% (weight of keratinase lyophilisat/final volume); substrate concentration, 4.9% (weight of nail powder/final volume) and a 6 h 10 min incubation time for nails.

Algorithms↗

PubMed1999

Ethambutol-sugar hybrids as potential inhibitors of mycobacterial cell-wall biosynthesis.

Ethambutol is an established front-line agent for the treatment of tuberculosis, and is also active against Mycobacterium avium infection. However, this agent exhibits toxicity, and is considered to have low potency. The action of ethambutol on the mycobacterial cell wall, particularly the arabinan, and comparison of the structure of ethambutol with several of the cell-wall saccharides, suggested that ethambutol-saccharide hybrids might lead to agents with a more selective mechanism of action. To this end, eight ethambutol-saccharide hybrids were synthesized and screened against M. tuberculosis and several clinical isolates of M. avium.

Antitubercular Agents↗

PubMed1999

Sampling field heterogeneity at the heme of c-type cytochromes by spectral hole burning spectroscopy and electrostatic calculations.

We report on a comparative investigation of the heme pocket fields of two Zn-substituted c-type cytochromes-namely yeast and horse heart cytochromes c-using a combination of hole burning Stark spectroscopy and electrostatic calculations. The spectral hole burning experiments are consistent with different pocket fields experienced at the hemes of the respective cytochromes. In the case of horse heart Zn-cytochrome c, two distinguishable electronic origins with different electrostatic properties are observed. The yeast species, on the other hand, displays a single electronic origin. Electrostatic calculations and graphics modeling using the linearized finite-difference Poisson-Boltzmann equation performed at selected time intervals on nanosecond-molecular dynamics trajectories show that the hemes of the respective cytochromes sample different potentials as they explore conformational space. The electrostatic potentials generated by the protein matrix at the heme show different patterns in both cytochromes, and we suggest that the cytochromes differ by the number of "electrostatic substates" that they can sample, thus accounting for the different spectral populations observed in the two cytochromes.

Animals↗

PubMed1999

Detection of circulating tumour cells in patients with breast or ovarian cancer by molecular cytogenetics.

Detection of micrometastases in patients with solid tumours may aid the establishment of prognosis and development of new therapeutic approaches. This study was designed to investigate the presence and frequency of tumour cells in the peripheral blood (PB) of patients with breast or ovarian cancer by using a combination of magnetic activated cell sorting (MACS) and fluorescence in situ hybridization (FISH). Separated tumour cell and PB-samples from 48 patients (35 breast cancers, 12 ovarian tumours, one uterine sarcoma) were analysed for the presence of numerical aberrations of chromosomes 7, 12, 17 and 17 q11.2-q12. Twenty-five patients had primary disease and 23 had relapsed. The technique allows the detection of one tumour cell in 106 normal cells. Circulating tumour cells were detected in 35/48 cases (17 patients had relapsed and 13 primary carcinoma with lymph node or solid metastases) by the expression of anti-cytokeratin and the presence of numerical chromosomal abnormalities. PB-tumour cells of patients with a primary carcinoma and without solid metastases had a significantly lower percentage of chromosomal aberrations, especially for chromosome 12 (P = 0.035; P = 0.038) compared to those with relapsed disease and solid metastases. Detection and quantification of minimal residual disease may monitor the response to cytotoxic or hormonal therapy and may identify women at risk of relapse.

Adult↗

PubMed1999

Expression of mucosa-related integrin alphaEbeta7 on alveolar T cells in interstitial lung diseases.

The expression of alphaEbeta7 integrin has been related to the selective retention of lymphocytes in mucosal tissues of gut, urogenital tract and lung. To identify potential disease-associated alphaEbeta7 expression patterns on cells accounting for lymphocytic alveolitis in interstitial lung disease (ILD), alphaE expression on CD4+ and CD8+ T cell subsets was evaluated by dual-colour flow cytometry in peripheral blood and bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF; n = 18), hypersensitivity pneumonitis (HP; n = 20) and sarcoidosis (n = 44) in comparison with healthy controls (n = 15). In both healthy individuals and all patient groups the proportion of alphaE-bearing T cells in peripheral blood was < 2%, whereas the vast majority of alveolar CD8+ T cells consistently co-expressed alphaE. Absolute alveolar CD8+alphaE+ cell numbers/ml were up to 30-fold increased in HP patients. Proportions of alphaE-bearing CD4+ cells in BALF were significantly elevated in IPF (74.0 +/- 2.7%) and HP (70.0 +/- 2.4%) compared with normals (30.0 +/- 1.8%) (mean +/- s.e.m.; P < 0.01). In sarcoidosis, the alphaE expression on BALF CD4+ cells displayed subgroup dependency: proportions significantly lower than normal were noted in chest radiographic stage I (14.3 +/- 1.5%), but increased proportions in stages II (50.0 +/- 3.8%) and III (64.0 +/- 4.8%). Correlations between common markers of T cell activation or BALF transforming growth factor-beta (TGF-beta ) bioactivity and alphaE expression were not noted. We conclude that the vast majority of alveolar CD8+ T cells consistently express alphaEbeta7 and that distinct patterns of alphaEbeta7 expression on alveolar CD4+ lymphocytes in sarcoidosis are related to the diverse manifestations of the sarcoid inflammatory process in the lung.

Adolescent↗

PubMed1999

[Assessing the quality of life after pancreas-kidney transplantation].

The pancreas-kidney transplantation strives for a reestablishment both of the physiological regulation of blood glucose levels without external insulin and of kidney function without the need of dialysis. Nevertheless, the postoperative morbidity of the combined transplantation is high. In long lasting diabetes type I, a strict selection of transplant candidates is necessary to minimize the risks of cardio-vascular complications. Between 1990 and 1997 only 17 of 44 patients really were accepted for transplantation in our unit. 13/17 patients are actually independent from external insulin and dialysis. Two other patients are free of dialysis, but the pancreas transplants had to be removed due to thrombosis or infection. In one case therapy-resistant acute rejection occurred and both organs had to be removed after two months. One women died four years after transplantation with a functioning kidney graft from myocardial infarction. 10 patients with stable transplant function are at work again. After normal pregnancy two women gave birth to healthy children, in one case twins. Drug regimen and outpatients visits are not seen as significant restrictions of the quality of life.

Adolescent↗

PubMed1998

Detection of chromosomal aberrations in tumor cells and tumor infiltrating lymphocytes by molecular cytogenetics in patients with gynecological cancer.

Conventional cytogenetic studies of tumor cells from patients with breast or ovarian cancer have shown multiple chromosomal abnormalities including chromosomes 7, 12, and 17. This study was designed to analyze the cytogenetic features of tumor cells and tumor infiltrating lymphocytes (TILs) by using a combination of magnetic activated cell sorting (MACS) and fluorescence in situ hybridization (FISH). Tumor cell, peripheral blood (PB), and TIL samples from 37 patients (20 ovarian tumors, 13 breast cancers, 3 uterine sarcoma, 1 carcinoma of the filamentary tube) were analyzed for the presence of numerical aberrations of chromosomes 7, 12, and 17. All of the tumor cells showed a high frequency of numerical aberrations of chromosomes 7, 12, and 17, especially trisomies or tetrasomies. There was no statistically significant difference in the incidence of chromosomal abnormalities in tumor tissue and effusions, or between primary and relapsed disease in patients with breast or ovarian tumors. However, tumor cells from patients with solid metastatic disease had significantly higher numbers of aberrations of chromosome 7 in the primary tumor than in tumors from patients without metastases (P = 0.049), suggesting that chromosome 7 is frequently involved in the progression of disease. Monosomies and trisomies of chromosomes 7 and 12 also occurred at a low percentage of TILs without any statistically significant difference between primary and relapsed tumors. The presence of these aneuploidies might be responsible for treatment failures in the immunotherapy of gynecological cancer.

Adult↗

PubMed1998

Proteins in electric fields and pressure fields: basic aspects.

This paper emphasizes the basic aspects of the interactions of chromoproteins at low temperatures with external pressure fields and electric fields. We discuss how the respective spectral properties can be modified and what we can learn from the spectral changes about the thermodynamic, electrostatic, functional and structural properties of proteins. A few examples are discussed in more detail.

Electricity↗

PubMed1998

Auxiliary liver transplantation with arterialization of the portal vein for acute hepatic failure.

Six adult patients suffering from acute hepatic failure and with a high urgent status underwent heterotopic auxiliary liver transplantation. In four of these patients, the portal vein of the liver graft was arterialized in order to leave the native liver and the liver hilum untouched and to be able to place the liver graft wherever space was available in the abdomen. The arterial blood flow via the portal vein was tapered by the width of the anastomosis. Two patients died, one of sepsis on postoperative day 17 (POD), the other after 3 months due to a severe CMV pneumonia. There were no technically related deaths. The native liver showed early regeneration in all cases. In one patient, the auxiliary graft was removed 6 weeks after transplantation. Four weeks later, he had to undergo orthotopic retransplantation due to a recurrent fulminant failure of the recovered native liver. This patient is alive more than 1 year after the operation. We conclude that heterotopic auxiliary liver transplantation with portal vein arterialization is a suitable approach to bridging the recovery of the acute failing native liver.

Acute Disease↗

PubMed1998

Methodological issues of human experimental research with hallucinogens.

Human experimental research with hallucinogenic drugs is potentially able to identify linking variables between the psycho(patho)logical conditions and neurobiological alterations involved in both pharmacologically induced and naturally occurring acute psychotic states. A number of methodological aspects should be considered when planning modern experimental studies with hallucinogenic drugs. The issues of subject selection, repeated measures, and adequate control groups are discussed in this paper. Examples of recent experimental studies are presented which take these aspects into account. The first study examined psychopathological changes, facial expression and semantic priming effects during a psilocybin-induced state. In the second study, semantic priming effects after intake of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE), and d-methamphetamine were investigated. Results confirmed time-dependent effects of psilocybin and the restriction of increased priming effects in the psilocybin group.

Consciousness↗

PubMed1998

An unusual case of Hughes-Stovin syndrome.

In 1959 HUGHES and STOVIN described a syndrome consisting of multiple pulmonary aneurysms and peripheral venous thrombosis. Since that time several cases of the Hughes-Stovin syndrome have been published. We present the case of a 25 yr old man who, in addition to the classical symptoms, had multiple aneurysms of the bronchial arteries, which were the cause of severe haemoptysis. An aneurysm of the left hepatic artery was also detected. To our knowledge this is the first description of aneurysms of the bronchial arteries in Hughes-Stovin syndrome. Bleeding was successfully treated by double embolization of bronchial arteries via transfemoral catheter.

Adult↗

PubMed1998

[Results of selective goiter resection in functional autonomy].

In the period from 1989 to 1994 a surgical treatment of toxic nodular goiter was performed in 145 patients. An unifocal autonomous adenoma occurred in 69 cases, a multifocal disease 76 times. The operative strategy consisted in a bilateral resection 105 times, and unilateral resection 29 times. An excision of a single node was carried out in ten cases. In one operation a hemithyroidectomy on one side and a subtotal resection of the other lobe was done. In May 1996 an interrogation about the current thyroid function was performed. In 105 (72.4%) patients a re-evaluation was possible. Concerning the postoperative therapy for prevention of recurrent hyperthyroidism or goiter growth, 84 patients (80%) had been treated with thyroxin and/or iodine. Under this therapy, after a mean period of 36 months 94 patients (89.5%) were clinically euthyroid. Nine patients (8.6%) were hypothyroid. Two patients developed a recurrent hyperthyroidism. Both of them belonged to the group of patients with multifocal autonomies, and both had been treated with thyroxin postoperatively. In one case, recurrent goiter growth occurred that did not need a therapeutic intervention. This patient as well had been treated for a multinodular goiter originally. She had not been taking a specific medication postoperatively. We conclude that a functional resection of autonomic tissue in nodular goiters is efficient in controlling the thyroid metabolism. A medical prophylaxis was not able to prevent recurrent hyperthyroidism in two cases.

Female↗

PubMed1998

Computer-assisted histometric analysis of tissue-engineered ovine bone.

OBJECTIVE: To develop a computer-assisted histometric technique that quantitatively determines the amount of regenerating bone, while excluding fibrovascular tissue and void spaces, in tissue-engineered bone constructs. To this end, a histometric technique was developed that couples digital tiling with adaptive, multiband color thresholding (AMBCT). STUDY DESIGN: To test the technique, a previously described model bone tissue-engineered construct filled with morcellized bone graft was employed. Histometric techniques were applied to quantify the amount of bone formed following eight weeks of implantation. RESULTS: The histometric technique was able to yield quantitative information regarding the amount of bone despite intrahistologic and interhistologic differences in staining. The technique is user friendly and highly automated. In addition to area fractions, the technique can provide bone ingrowth profiles as a function of geometry and implantation time. CONCLUSION: Digital tiling coupled with AMBCT offers an easy, fast and reproducible technique that aids in quantification of bone within histologic sections. In addition, the technique can be adapted to quantification of other tissues. Further studies are under way to investigate the potential of correlating the histometric technique with mechanical strength analyses of tissue-engineered bone specimens.

Animals↗

PubMed1997

Rescue therapy with tacrolimus in simultaneous pancreas/kidney transplantation.

Tacrolimus has been effective both in primary and rescue therapy following steroid and OKT3-resistant acute rejection in liver and kidney transplantation. Due to the effects of tacrolimus on glucose metabolism, there has been concern about its use in simultaneous pancreas/kidney transplantation. We report on the results of six patients (three female, three male, age 35.2 +/- 7.3 years) converted from cyclosporin A to tacrolimus following simultaneous pancreas/kidney transplantation in steroid-resistant acute rejection. Tacrolimus was induced 2.8 +/- 1.7 months (range 1-4.8 months) after transplantation; follow-up was 3-18 months. Following conversion, creatinine levels declined in all patients [3.5 +/- 1.2 mg/dl before conversion, 3.0 +/- 1.9 mg/dl (n = 6) at three months, 1.4 +/- 0.1 mg/ dl at 1 year (n = 3)]. Before conversion, fasting blood glucose levels averaged 154 +/- 33 mg/dl, with three patients receiving insulin. Three months later no patient required insulin, the mean glucose level being 107 +/- 23 mg/dl (n = 6); at 1 year it was 92 +/- 9 mg/dl (n = 3). One patient lost his pancreatic graft after 4 months due to a mycotic aneurysm. We conclude that conversion to tacrolimus is a safe and effective treatment in cases of steroid-resistant rejections following pancreas/ kidney transplantation.

Administration, Oral↗

PubMed1997

Successful regrafting of a transplanted liver.

We report on the successful regrafting of a transplanted liver. The donor liver was first grafted into a patient suffering from cryptogenic cirrhosis; the patient died 1 day after the elective transplantation of cerebral bleeding. The well-functioning graft was harvested again and transferred to our institution. After another 12 h of cold ischemia, the liver was reperfused in an urgently registered patient with recurrence of hepatitis B in his first graft. The transplantation was successfully performed and the patient is now doing well, more than 5 months after regrafting with the reused liver.

Humans↗