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Biomedical subjects

P Hoffmann

Publications and source records attributed to P Hoffmann.

At least 127 records · Page 7Linked to original sources

Organ culture of human lymphoid tissue. I. Characteristics of the system.

The major aim of three-dimensional tissue culture is to preserve the natural architecture of the tissue and thereby allow the cells to retain their original functions during in vitro cultivation. Here we describe a method for the rapid preparation of three-dimensional tissue explants from human lymphoid organs. The precision-cut tissue slices are of uniform size and thickness and can be cryopreserved and stored in liquid nitrogen without substantial loss of viability or functionality of the cells. Upon in vitro culture, cells within the explants survived as well as their counterparts cultured in single cell suspension. However, spontaneous immunoglobulin (Ig) production in explants started more promptly and often reached considerably higher levels than that in suspension cultures run in parallel. Lymphocytes within the slices could be activated by polyclonal stimuli such as PHA, as shown by the upregulation of the activation markers CD23 and CD25 on B and T cells, respectively. However, approximately five-fold higher concentrations of mitogen than those used for suspension cultures were needed. Taken together, the system presented here constitutes a potent tool for the investigation of the complex interactions leading to activation and differentiation of B and T cells in lymphoid organs.

Antibody Formation↗

Up-regulation of insulinlike growth factor I binding sites in experimental colitis in rats.

BACKGROUND/AIMS: The gastrointestinal tract is a major target of insulinlike growth factor (IGF) I. IGF-I binds to two different receptors and to binding proteins (IGFBPs), which act as carriers and mediators. This study investigated the regulation of IGF-I binding sites in rat colitis. METHODS: Colitis was induced by colonic instillation of 2,4,6-trinitrobenzenesulfonic acid in ethanol. IGF-I binding sites in colon sections were localized by incubation with 125I-IGF-I. The contribution of binding to the IGF-I receptor was estimated by competition with unlabeled IGF-I, IGF-II, and insulin. Colonic RNA was screened for IGFBPs by Northern hybridization. RESULTS: IGF-I binding sites were increased more than two-fold in the muscularis propria of inflamed colon as soon as 12 hours and up to 1 week after injury. Insulin could not displace this elevated level of binding, even though it could displace IGF-I from the mucosa and muscularis mucosa. Northern hybridization showed a 2-3-fold increase in IGFBP-4 and IGFBP-5 messenger RNA from inflamed colon. CONCLUSIONS: Experimental colitis in rats causes an increase in IGF-I binding to the muscularis propria, which represents increased levels of IGFBP-4 and IGFBP-5. These data suggest an important role for IGFBPs in modulating IGF effects during inflammation and tissue repair.

Animals↗

Nonlinear polarization spectroscopy in the frequency domain of light-harvesting complex II: absorption band substructure and exciton dynamics.

Spectral substructure and ultrafast excitation dynamics have been investigated in the chlorophyll (Chl) a and b Qy region of isolated plant light-harvesting complex II (LHC II). We demonstrate the feasibility of Nonlinear Polarization Spectroscopy in the frequency domain, a novel photosynthesis research laser spectroscopic technique, to determine not only ultrafast population relaxation (T1) and dephasing (T2) times, but also to reveal the complex spectral substructure in the Qy band as well as the mode(s) of absorption band broadening at room temperature (RT). The study gives further direct evidence for the existence of up to now hypothetical "Chl forms". Of particular interest is the differentiated participation of the Chl forms in energy transfer in trimeric and aggregated LHC II. Limits for T2 are given in the range of a few ten fs. Inhomogeneous broadening does not exceed the homogeneous widths of the subbands at RT. The implications of the results for the energy transfer mechanisms in the antenna are discussed.

Circular Dichroism↗

[Treatment guidelines in various stages of senile retinoschisis].

BACKGROUND: Concerning the indications, progression in course and the possible complications, the different methods of treatment in cases of retinoschisis in its different expressions were examined. A staging of senile retinoschisis is presented. PATIENTS: Patients' natural course, prophylactic treatment against expansion and treatment of retinal detachment were examined. RESULTS: The lateral and central barrier of laser or cryo around the schisis is contradictory since a progression in direction to the macula is the result. Three of such cases could be found. In 6 of 52 cases with prophylactic treatment of an outer layer defect with cryo the result was a schisis detachment. In all these cases a retinal reattachment was performed with the Custodis procedure. The final anatomic result of 95 treated schisis retinal detachments was a 98% success. The symptomatic or progressive cases had a little less favourable outcome. CONCLUSIONS: The only indication for treatment of a schisis at present is the symptomatic or progressive schisis detachment with threatening of the macula. Lateral or central barring of a schisis or treatment of the borders of an outer layer retinal break should be avoided. The rate of reattachment and the functional results are better than in the group of rhegmatogenous retinal detachments including the 50.5% schisis retinal detachments without symptoms.

Adult↗

Effect of antiemetic therapy on recovery and hospital discharge time. A double-blind assessment of ondansetron, droperidol, and placebo in pediatric patients undergoing ambulatory surgery.

BACKGROUND: Postoperative nausea and vomiting continue to be a significant problem for pediatric ambulatory surgery patients. Although ondansetron has been demonstrated to be effective in the prophylactic treatment of postoperative nausea and vomiting (surrogate end point) no one has demonstrated a benefit of antiemetic therapy on patient recovery, postanesthesia care unit length of stay, and hospital length of stay (nonsurrogate end points). In a double-blind manner, the effects of ondansetron, droperidol, and placebo on the incidence of emesis, postanesthesia care unit stay, and hospital discharge time were evaluated in children undergoing dental surgery. METHODS: The subjects were 102 children aged 2-8 years undergoing complete dental restoration. All patients received midazolam before undergoing inhalation induction of anesthesia with N2O/O2 and halothane. Anesthesia was maintained with N2O/O2 and alfentanil. Patients were then randomized to receive ondansetron (0.1 mg/kg), droperidol (75 micrograms/kg), or placebo (normal saline) in a double-blind fashion. At the conclusion of the anesthesia, a trained nurse observer assessed patient recovery and recorded the time patients met specified criteria for postanesthesia care unit and hospital discharge as well as episodes of emesis in the hospital and at home during the first 24 hr after surgery. RESULTS: Ninety-five patients completed the study. The three antiemetic groups were similar with respect to age, weight, length of surgery, dose of alfentanil, and route of preanesthetic medication. The 24-hr incidence of emesis was significantly less with ondansetron (9%) than with placebo (35%) or droperidol (32%). Ondansetron-treated patients had significantly shorter hospital stays than droperidol-treated patients, but recovery parameters were similar between the ondansetron- and placebo-treated patients. CONCLUSIONS: Ondansetron is an effective prophylactic antiemetic agent for children undergoing dental surgery. Compared with droperidol, ondansetron decreases the length of hospital stay, but compared to placebo, there were no differences in the patient recovery parameters.

Ambulatory Surgical Procedures↗

Inactivation of a Synechocystis sp strain PCC 6803 gene with homology to conserved chloroplast open reading frame 184 increases the photosystem II-to-photosystem I ratio.

A gene of the unicellular cyanobacterium Synechocystis sp strain PCC 6803 that is homologous to the conserved chloroplast open reading frame orf184 has been cloned and sequenced. The nucleotide sequence of the gene predicts a protein of 184 amino acids with a calculated molecular mass of 21.5 kD and two membrane-spanning regions. Amino acid sequence analysis showed 46 to 37% homology of the cyanobacterial orf184 with tobacco orf184, rice orf185, liverwort orf184, and Euglena gracilis orf206 sequences. Two orf184-specific mutants of Synechocystis sp PCC 6803 were constructed by insertion mutagenesis. Cells of mutants showed growth characteristics similar to those of the wild type. Their pigment composition was distinctly different from the wild type, as indicated by an increase in the phycocyanin-to-chlorophyll ratio. In addition, mutants also had a two- to threefold increase in photosynthetic electron transfer rates as well as in photosystem II-to-photosystem I ratio-a phenomenon hitherto not reported for mutants with altered photosynthetic characteristics. The observed alterations in the orf184-specific mutants provide strong evidence for a functional role of the orf184 gene product in photosynthetic processes.

Amino Acid Sequence↗

Isoflurane narcotherapy in depressive patients refractory to conventional antidepressant drug treatment. A double-blind comparison with electroconvulsive treatment.

This is the first report on a controlled study comparing the therapeutic and non-therapeutic (side) effects of electroconvulsive treatment (ECT) and isoflurane narcotherapy (ISONAR; deep anesthesias with the inhalation of anesthetic isoflurane) in drug-refractory, severely depressed women, who had been randomly allocated either to ECT (n = 10) or ISONAR (n = 10). Patients from each group were subjected to a total of six treatment sessions (two sessions per week) and maintained on a fixed antidepressant drug dose. The antidepressant efficacy of either treatment was evaluated for each treatment session (in search of a 'rapid antidepressant effect') and at weekly intervals. Cognitive functions or signs of an organic brain syndrome were evaluated by means of psychological tests and extensive EEG analyses. Rapid antidepressant effects of the first treatment session were only significant in patients on ISONAR; in the subsequent treatment sessions, ECT also induced rapid antidepressant effects. Antidepressant effects during the treatment period were comparable, and patients on ISONAR improved further during follow-up, whereas patients on ECT tended to relapse. ISONAR-treated patients improved in most psychometric variables, whereas patients on ECT deteriorated. Finally, the EEG patterns of the ISONAR-treated patients remained normal or augmented (dominant alpha power), whereas patients on ECT developed an increase in abnormalities in EEG patterns and theta/delta power. This indicates an organic brain syndrome in patients on ECT.

Adult↗

Arachidonic acid supplementation enhances hydrogen peroxide induced oxidative injury of neonatal rat cardiac myocytes.

OBJECTIVE: Selective fatty acid supplementation of non-myocardial cells has been reported to enhance oxidative injury. The purpose of this study was to extend this research by determining if supplementation of isolated cardiac myocytes with arachidonic acid increases myocyte sensitivity to H2O2 induced lipid peroxidation and cytotoxicity. METHODS: Myocytes were supplemented with arachidonic acid by complexing it with calf serum and adding it to myocytes at a final concentration of 0, 50, or 100 microM for 36 h. Myocytes were then exposed to 50 or 100 microM H2O2 for 1 h and lipid peroxidation and cytotoxicity were assessed by measuring thiobarbituric acid reactive substances and lactate dehydrogenase release into culture medium. To determine if unesterified arachidonic acid contributed to oxidative injury, 100 microM arachidonic acid was added directly to cultured myocytes in serum-free buffer. Vitamin E and desferrioxamine were assessed for their ability to protect against oxidative injury induced by unesterified arachidonic acid or H2O2. RESULTS: Supplementation with 100 microM arachidonic acid for 36 h increased the arachidonic acid content of phospholipids from 0.58(SD 0.06) to 0.90(0.19) nmol.nmol-1 lipid phosphorus. A 1 h exposure to H2O2 induced lipid peroxidation and cytotoxicity in a concentration dependent manner. Pretreatment of myocytes with 10 microM vitamin E or 1 mM desferrioxamine prevented H2O2 induced effects. Arachidonic acid supplementation at 50 or 100 microM significantly enhanced lipid peroxidation induced by 100 microM H2O2, whereas cytotoxicity was increased only in myocytes supplemented with 100 microM arachidonic acid. Addition of unesterified arachidonic acid directly to cultured myocytes caused marked cytotoxicity and lipid peroxidation which were prevented by vitamin E or desferrioxamine. CONCLUSIONS: Arachidonic acid supplementation of cardiac myocytes modifies fatty acid content of phospholipids and enhances the susceptibility of myocytes to H2O2 induced oxidative injury.

Animals↗

[Value of endocervical curettage in colposcopic diagnosis of cervix diseases].

The present study was undertaken to determine the credibility of endocervical curettage as a part of evaluation of patients with abnormal Pap smears. A series of 108 patients were carefully examined with colposcopy, ectocervical biopsies and endocervical curettage, and all of them underwent cervical conization following diagnostic study. The histologic diagnosis results between endocervical curettage and cervical cone was compared. The estimate was 85% for sensitivity, 35% for specificity, 62% for positive predictive value and 65% for negative predictive value of cervical curettage. The observations suggest that endocervical curettage credibility is poor and we need to asses the outpatient evaluation and treatment carefully.

Adenocarcinoma↗

[Pathogenesis and pathophysiology of sigmoid diverticulitis].

The sigmoid colon is the part of the large intestine which is most commonly involved in diverticular disease due to its anatomical properties. True diverticula containing all layers of the colonic wall are rare. The majority of diverticula found are pseudodiverticula. They are herniations of mucosa and submucosa through clefts in the colonic muscle layers as a result of morphologic changes of the colonic wall and an imbalance between the intraluminal pressure and the pressure in the abdominal cavity. Microperforations of the tip of the diverticula are an important factor leading to inflammation and symptomatic disease.

Colonic Diseases↗

Arachidonic acid disrupts calcium dynamics in neonatal rat cardiac myocytes.

OBJECTIVES: The purpose of this study was to investigate the effects of prolonged arachidonic acid (AA) exposure on electrically induced fluctuations of cytosolic free Ca2+ concentration ([Ca2+]i) in cardiac myocytes and to identify intracellular biochemical events that may play a role in the actions of AA on [Ca2+]i dynamics. METHODS: Electrically induced [Ca2+]i transients were investigated in cultured single neonatal rat ventricular myocytes using spectrofluorometric analysis of fura-2-[Ca2+]i binding. KCl-induced depolarization, caffeine and ryanodine were used to assess the effects of AA on Ca2+ handling by the sarcolemma and the sarcoplasmic reticulum. Prostanoid formation was measured with an ELISA technique. alpha-Tocopherol was used to determine if free radical formation was a factor in the AA effects on [Ca2+]i. RESULTS: Exposure to 10-30 microM AA produced a concentration-dependent and reversible configuration change and eventually a cessation of [Ca2+]i transients. Continued exposure resulted in a Ca2+ overload (tonic [Ca2+]i greater than peak systolic [Ca2+]i). AA did not influence KCl-induced [Ca2+]i increase but did eliminate caffeine-induced [Ca2+]i transients. AA exposure stimulated the formation of 6-oxo-prostaglandin F1 alpha in a concentration-dependent manner, but thromboxane B2 formation was not influenced. alpha-Tocopherol pretreatment significantly delayed times till cessation of [Ca2+]i transients and Ca2+ overload, whereas ryanodine and cyclo-oxygenase inhibitors were without effect. CONCLUSIONS: The present data provide evidence that the initial action of AA on [Ca2+]i transients during excitation-contraction coupling involves an effect of AA on sarcolemmal Ca2+ influx and sarcoplasmic reticulum Ca2+ handling. AA-induced cessation of electrically induced [Ca2+]i transients and Ca2+ overload may involve the formation of free radicals.

6-Ketoprostaglandin F1 alpha↗

Depression of calcium dynamics in cardiac myocytes--a common mechanism of halogenated hydrocarbon anesthetics and solvents.

Individual halogenated hydrocarbons (HC) have recently been demonstrated to depress Ca2+ dynamics in cardiomyocytes during excitation-contraction coupling. In the present study, eight widely used HC were systematically compared for their effects on Ca2+ dynamics in neonatal rat cardiomyocytes by means of spectrofluorometric analysis of fura-2-Ca(2+)-binding. Cells were exposed to dichloromethane (DCM), dichloroethane (DCE), 1,1,2-trichloroethane (112-TCE), trichloroethylene (TRI), halothane (HAL), 1,1,1-trichloroethane (111-TCE), perchloroethylene (PER), or pentachlorethane (PCE) in an environmentally controlled chamber. All HC tested decreased the height of electrically induced cytosolic free Ca2+ ([Ca2+]i) transients in a concentration-dependent and reversible manner (IC50 0.15-18.06 mM) without significant effects on diastolic [Ca2+]i. The increase in [Ca2+]i induced by depolarization with 90 mM KCl was inhibited to a lesser degree. Investigations with thapsigargin (100 nM) and ryanodine (1 microM)-inhibitors of Ca2+ release from the sarcoplasmic reticulum-provided evidence that the tonic Ca2+ response after KCl depolarization depends mainly on sarcolemmal Ca2+ influx. The potency of the eight HC to inhibit Ca2+ dynamics in cardiomyocytes correlated with their octanol/water partition coefficients. Results support the hypothesis that alteration of Ca2+ dynamics in cardiomyocytes is a common mechanism of cardiotoxic HC actions.

Anesthetics↗

The subjective, behavioral and cognitive effects of subanesthetic concentrations of isoflurane and nitrous oxide in healthy volunteers.

A prospective, crossover, double-blind trial was conducted in nine healthy volunteers in which the subjective, psychomotor and memory effects of isoflurane (0.0, 0.3 and 0.6%) and nitrous oxide (N2O) (0, 20 and 40%) were examined. Dependent measures included visual analog scales and a standardized drug effects inventory (subjective effects), reaction time and eye-hand coordination (e.g., psychomotor performance), and immediate and delayed free recall (memory). There were some similarities in subjective effects between the two inhaled drugs (e.g., increased ratings of "drunk" and "spaced out"), but isoflurane had effects which N2O did not have. Isoflurane but not N2O increased visual analog scale ratings of "confused," "sedated," and "carefree," and decreased ratings of "in control of thoughts" and "in control of body." An odor was detected with isoflurane and it was disliked. Psychomotor performance was more grossly impaired during isoflurane inhalation than during N2O inhalation. Psychomotor recovery from both agents was rapid and complete so that 5 min after the inhalation period had ceased, performance had returned to baseline levels. Both isoflurane and nitrous oxide impaired immediate and delayed free recall. The feasibility of using isoflurane in conscious sedation procedures is discussed.

Adult↗

Protective effect of epidermal growth factor in an experimental model of colitis in rats.

BACKGROUND/AIMS: The role of epidermal growth factor (EGF) in the maintenance of mucosal integrity in the lower gastrointestinal tract is unknown. The aim of this study was to determine the effect of EGF in experimental colitis. METHODS: Colitis was induced with 2,4,6-trinitrobenzenesulfonic acid/ethanol enemas. Rats were pretreated with intraperitoneal administration of recombinant human EGF (600 micrograms/kg) or vehicle 1 hour before induction of colitis and daily thereafter until killed at 8 hours, 48 hours, and 1 week. A separate group received an identical dosage and administration of EGF or vehicle for 1 week with treatment initiated 24 hours after the induction of colitis. Colonic tissue was evaluated macroscopically, histologically, and for myeloperoxidase activity. RESULTS: Pretreatment with EGF reduced microscopic erosions at 8 and 48 hours by 74% and 54%, respectively (P < 0.05). At 1 week, microscopic ulcerations and myeloperoxidase activity were reduced by 65% in the EGF-pretreated group (P < 0.05). No significant difference in macroscopic injury, histological damage, or myeloperoxidase activity was noted when EGF treatment was initiated after the induction of colitis. CONCLUSIONS: Systemic EGF administration reduces mucosal damage and inflammation in a trinitrobenzenesulfonic acid/ethanol model of colitis in rats through a mechanism involving mucosal protection.

Animals↗

Effects of long-lasting voluntary running on the cerebral levels of dopamine, serotonin and their metabolites in the spontaneously hypertensive rat.

The brain regional dopamine (DA) and serotonin (5-HT) levels and turnover were studied in the spontaneously hypertensive rat (SHR), following voluntary, long-lasting (7 weeks) wheel-running exercise. Groups of rats were sacrificed 1-2 h, 23-24 h or 47-48 h after termination of the last running session, and the cerebral tissue levels of 5-HT, 5-HIAA, DA and DOPAC were determined and compared to corresponding levels obtained in sedentary controls. In the exercised animals, there was a selective decrease in the limbic forebrain levels of DOPAC in the immediate post-exercise period (1-2 h), while the DA turnover (DOPAC/DA ratio) was not altered. In addition, the 5-HT and 5-HIAA levels in the serotoninergic nerve terminal limbic forebrain and the 5-HT turnover (5-HIAA/5-HT ratio) in the cell body-containing brain stem areas were decreased in the immediate post-exercise period. No significant changes in the DA, DOPAC, 5-HT or 5-HIAA levels, nor in the DA and 5-HT turnover, were obtained in the remainder of the brain regions analyzed, regardless of time after termination of running. Taken together, the present study indicates that voluntary exercise in the SHR gives rise to differentiated regional effects on brain DA and 5-HT levels and turnover, thus supporting the view that changes in central monoaminergic activity are involved in the functional effects of long-term exercise. Interestingly, the psychomotor-associated limbic forebrain areas appeared particularly susceptible.

3,4-Dihydroxyphenylacetic Acid↗