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Biomedical subjects

G Gross

Publications and source records attributed to G Gross.

At least 109 records · Page 6Linked to original sources

[Elective lymph node dissection in malignant melanoma--status of color Doppler findings].

Since there is still a controversial discussion about the ELND in melanoma patients, the purpose of this prospective study was to optimize the indication concerning ELND by ultrasound examinations. 144 patients with primary melanomas were checked every 3 months after excision. Echomorphologic pattern and intranodal vascularisation in the color-flow Doppler modus provide essential information for differential diagnosis. We found 47 patients (32.6%) with suspicious ultrasound lesions. 50% of these patients had no pathological clinical findings, the histological findings of excised lymph nodes were positive in all cases. It must be emphasized, however, that the group with lymph node metastases included 12 patients with low-risk-melanomas (2 x Tis, 10 x T1 < 1 mm tumor thickness). In comparison with a historical control group (141 patients), where ELND was performed routinely in high-risk-patients ( > T2), the incidence of ELND in our hospital decreased more than 50%; at the same time the percentage of detected lymph node metastases increased (twice).

Adult↗

Heterologous expression as a tool for gene identification and analysis.

These days, genome research mainly concerns the accumulation of sequence data and their theoretical interpretation based on analogies to known genes, proteins and structures. However, a final identification of gene function can only be verified by experimental data. One step in this process is the expression of the isolated gene in pro- and eukaryotes. In this article we will review some of the basic features of expression in Escherichia coli and mammalian cells that are relevant to the design of expression experiments. Emphasis is put on the first instance of attaining a high enough level of expression in order to be able to detect the cellular effects or to isolate the product of the transferred gene.

Animals↗

Circadian rhythm of vital signs, norepinephrine, epinephrine, thyroid hormones, and cortisol in schizophrenia.

Changes in the circadian rhythmicity in vital signs, catecholamines, thyroid hormones, and cortisol have been observed in psychiatric disorders, most notably in depression. With respect to schizophrenia, the literature is scanty. We report here on the circadian parameter estimates of the vital signs, epinephrine, norepinephrine, triiodothyronine, thyroxine, thyroid stimulating hormone, and cortisol in the blood of 34 healthy subjects, 89 drug-free schizophrenic patients, and 25 neuroleptic-treated schizophrenic patients. The analyses are based on the cosine model to fit the experimental data. The circadian profiles of heart rate, blood pressure, and oral temperature are similar among schizophrenic patients and healthy subjects. Neuroleptic-treated patients have significantly higher MESORs (the daily mean) of serum norepinephrine and epinephrine than healthy subjects. The TSH MESOR is significantly lower in schizophrenic patients; the MESOR of triiodothyronine also shows a tendency to be nonsignificantly lower in schizophrenic patients compared with control subjects. The circadian serum thyroxine and cortisol profiles are similar in the three groups. The data show that the circadian profiles of vital signs in drug-free chronic schizophrenic patients who are not chronically hospitalized are similar to those of healthy subjects and that the increase in serum catecholamines and the apparent lowering in some thyroid indices might induce a down-regulation in the noradrenergic receptor system that could contribute to the pathophysiology of schizophrenia.

Adolescent↗

Phospholipid-hydroperoxide glutathione peroxidase. Genomic DNA, cDNA, and deduced amino acid sequence.

The complete amino acid sequence of the selenoprotein phospholipid-hydroperoxide glutathione peroxidase (PHGPX) from pig heart has been deduced from the corresponding genomic DNA, the cDNA covering the coding region, and by sequencing the N terminus of the protein. The maximum length of the peptide chain derived from the cDNA amounts to 170 amino acid residues. By protein sequencing the N-terminal residues methionine and cysteine of the deduced sequence were found to be cleaved. The molecular mass of 19,671 Da obtained by laser desorption mass spectroscopy, however, significantly exceeds the mean molecular mass of 19,257.09 calculated for the sequence 3-170 of PHGPX, thus indicating posttranscriptional modification. In contrast to glutathione peroxidase (GPX) the coding area of the PHGPX gene is composed of seven exons. Only the amino acid sequences encoded by the third and fifth exon are highly homologous to GPX sequences. The amino acid residues selenocysteine, tryptophan, and glutamine forming the catalytic site in bovine GPX are conserved in homologous positions of PHGPX, whereas the arginine residues presumed to bind GSH in GPX are not. Gaps in the PHGPX sequence correspond to subunit interaction sites of the tetrameric GPX. The data suggest an identical catalytic mechanism of the selenoperoxidases, a less stringent substrate specificity of PHGPX, and explain the monomeric nature of PHGPX. As in other selenoproteins, the selenocysteine residue of PHGPX is encoded by UGA. The 3'-untranslated region (UTR) of the PHGPX shows a limited consensus with that of GPX and 5'-deiodinase, where it was shown to be responsible for the decoding of UGA as selenocysteine. The 3'-UTR of PHGPX can form a stem/loop as in other mammalian selenoprotein genes. The 5'-UTR and the first intron of the PHGPX gene contain a variety of putative regulatory elements indicating hormonal control.

Amino Acid Sequence↗

Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia.

Circadian rhythm abnormalities have been described mostly with respect to manic-depressive illness; little information is available concerning circadian rhythms and schizophrenia or their influence on neuroleptic drugs. We showed previously that the MESOR of dopamine is higher in schizophrenic patients than in healthy subjects and that women who are drug-free schizophrenic have lower prolactin MESORs and lower amplitudes than healthy women. We now report the data of a cosinor analysis of tryptophan, serotonin, melatonin, and pituitary hormones in the blood of 34 healthy subjects, 90 drug-free schizophrenics, and 25 neuroleptic-treated schizophrenic patients. This data indicated a significant phase advance of serum tryptophan, prolactin, and melatonin concentrations, a trend toward a phase advance in serotonin. Thyroid stimulating hormone (TSH), and growth hormone concentrations, and decreases in the TSH MESORs among patients compared to healthy subjects. These results suggest that circadian changes, such as phase advances and alterations in MESOR, are not only present in depression but also in schizophrenia. Although neuroleptic treatment raised the prolactin MESOR and amplitude, it did not elicit any change in circadian rhythmicity among the other parameters.

Adolescent↗

Treatment of atypical leishmaniasis with interferon gamma resulting in progression of Kaposi's sarcoma in an AIDS patient.

Visceral leishmaniasis (kala-azar) affecting HIV-infected patient is being reported in increasing frequency. A 40-year-old German bisexual patient with full-blown AIDS is described who presented with Kaposi's sarcoma, epigastric pain, diarrhea, and weight loss but without fever. Leishmania amastigotes were initially found in biopsies from stomach, duodenum, and a cutaneous Kaposi's sarcoma lesion but were later also recovered from bone marrow and lymph node. The patient received three courses of a combination of pentavalent antimony and interferon-gamma. In addition to the common side effects such as fever, thrombocytopenia, and elevated amylase and lipase, a vivid progression of the Kaposi's sarcoma was noted. Tumor progression was temporally closely associated with treatment with interferon-gamma. Because this phenomenon has also been observed in other patients, we advise caution when using interferon-gamma in patients with Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

Antibodies against linear and conformational epitopes of the human papillomavirus (HPV) type 16 E6 and E7 oncoproteins in sera of cervical cancer patients.

Sera obtained from 137 cervical cancer patients were analysed for the presence of antibodies to the human papillomavirus (HPV) type 16 proteins E6 and E7 by the aid of different assays, i.e. ELISA using as antigen either synthetic peptides or the complete E7 protein and radio-immunoprecipitation (RIPA) which uses the viral protein made by in vitro transcription/translation. In agreement with previous reports, reactivity to the E7 protein was found more frequently than to the E6 protein (31.4% vs. 16.8%) when the sera were assayed by peptide-based ELISA. In contrast, when RIPA was employed, reactivity to either protein was obtained at similar frequency (38.7% vs 46.7%). When the protein was denatured prior to immuno-precipitation the reactivity was lost in all sera tested for E6-specific antibodies but only in a few samples in the E7-RIPA. Therefore it was concluded that the increased sensitivity of the E6-RIPA as compared to the E6 peptide-ELISA is due to the detection of antibodies to conformational epitopes which are presented by the in vitro product but not by the synthetic peptides. Eighty-two sera from healthy donors were tested by HPV 16E6- and E7-RIPA and also by ELISA using the HPV 16E7 protein which was produced in the fission yeast Schizosaccharomyces pombe. One sample reacted each in the E6- and E7-RIPA indicating a high specificity of these assays. The E7 protein-ELISA proved to be less sensitive for the detection of antibodies in cervical cancer patients' sera (22.6% positive) as compared to peptide-based ELISA or RIPA.

Adolescent↗

Thrombolysis versus thrombectomy for occluded hemodyalisis grafts.

Graft thrombosis is the most frequent complication of polytetrafluoroethylene grafts for hemodialysis. Many of these patients arrive at the dialysis unit with fluid and metabolic abnormalities that require prompt dialysis. Rapid declotting of the graft is important to avoid having to create temporary access. Thrombolysis with urokinase has been evaluated by recent retrospective studies and found to be successful in 60% to 90% of cases. Our prospective, randomized trial was initiated to compare thrombolysis with standard surgical thrombectomy; and to evaluate the safety, effectiveness, efficiency, and durability of these modalities. In this study, 15 patients underwent thrombolysis and 16 had thrombectomy. The success rate was 67% for the thrombolysis group compared with 94% for the surgical group. Patency rates were similar for both modalities, but the complication rates were higher and the time to completion longer with thrombolysis. Although both treatments can be used successfully, surgical thrombectomy remains the optimal choice for treating occluded dialysis grafts.

Adult↗

Competence and responsibility in schizophrenia.

In a survey of the historical background it is shown that the classical doctrine on responsibility in schizophrenia has left its mark on the wordings of the psychiatric textbooks of the different countries. Closely combined with the imputation of enduring irresponsibility in schizophrenia was the opinion that civil rights are largely suspended if a person is given the diagnosis of schizophrenia. By the more recent research results of the studies of course and long-term outcome of schizophrenia and related psychoses and the development of the basic symptom concept has shown that it is not justified on principle to summarily deprive a person, diagnosed as schizophrenia, of civil rights as well as of criminal responsibility. New directions and some guidelines for an adequate assessment of competence and responsibility in schizophrenia are described. The knowledge of the newer findings and the application and utilization of the concept of basic symptoms and non-psychotic basic stages enable to overcome the doctrines of incurability, principle heterogeneity and numinous singularity and may lead to a rather appropriate and adequate social appreciation of the disease. Insight, freedom, responsibility, and competence of a person diagnosed as schizophrenia are in the postpsychotic pure residues and basic stages much more frequently preserved and available than hitherto assumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Civil Rights↗

Radioligand binding studies of alpha 1-adrenoceptor subtypes in rat heart.

1. In order to characterize the alpha 1-adrenoceptor subtypes mediating positive inotropic effects of adrenaline (in the presence of propranolol) in rat right ventricular strips and the Ca2+ sources used to elicit them, we have used radioligand binding to identify the alpha 1-adrenoceptor subtypes present in rat heart and the alpha 1-adrenoceptor affinity and subtype-selectivity of various pharmacological tools. 2. Amitryptiline, mianserin, trimipramine, oxaprotiline, clonidine, chloroethylclonidine, phenoxybenzamine, BE 2254 and 8-OH-DPAT competed for [3H]-prazosin binding in rat heart, vas deferens, liver, spleen, cerebral cortex and hippocampus but none of them displayed detectable alpha 1-adrenoceptor subtype-selectivity; nitrendipine did not compete for [3H]-prazosin binding in concentrations up to 5 mumol 1(-1). 3. The alpha 1 A-adrenoceptor-selective, 5-methyl-urapidil, (+)-niguldipine, and to a lesser extent (-)-niguldipine competed for [3H]-prazosin binding in rat heart, vas deferens, cerebral cortex and hippocampus with shallow and biphasic curves; analysis of these curves demonstrated that rat heart contains alpha 1A-and alpha 1B-adrenoceptors in a 20:80 ratio. 4. Treatment of rat right ventricular strips with 100 mumol l-1 chloroethylclonidine for 30 min at 30 degrees C followed by 60 min washout reduced the number of alpha 1-adrenoceptors, as assessed by [3H]-prazosin saturation experiments, by 74%. Treatment with 100 micromol l(-1) CdCl2 did not affect number or affinity of cardiac alpha 1-adrenoceptors and combined treatment with chlorethylclonidine and CdCl2 reduced alpha 1-adrenoceptor number by 90%. 5. Treatment of rat right ventricular strips with chloroethylclonidine steepened 5-methyl-urapidil competition curves and increased the relative contribution of alpha 1A-adrenoceptors from 26 to 89%. Treatment with CdCl2 did not affect 5-methyl-urapidil competition curves and combined treatment with chloroethylclonidineand CdCl2 increased the relative contribution of alpha lA-adrenoceptors to 66%.6. We conclude that rat heart contains alpha 1A- and alpha 1B-adrenoceptors in a 20:80% ratio. Treatment withchloroethylclonidine reduces alpha 1B-adrenoceptor number by 96% but has only minor effects on alpha 1A-adrenoceptor density. Treatment with CdCl2 does not affect the number of either alpha 1-adrenoceptor subtype.

Adrenergic alpha-1 Receptor Antagonists↗

Functional studies on alpha 1-adrenoceptor subtypes mediating inotropic effects in rat right ventricle.

1. We have studied the alpha 1-adrenoceptor subtypes mediating inotropic effects of adrenaline in rat right ventricle and the Ca2+ sources used to elicit these effects. alpha 1A-Adrenoceptor-mediated contractile effects in rat vas deferens were studied for comparison in some cases. 2. Treatment with chloroethylclonidine did not affect the maximal beta-adrenoceptor-mediated inotropic effects in rat right ventricle or the maximal alpha 1A-adrenoceptor-mediated contractile effects in rat vas deferens; it did not alter the potency of isoprenaline in the ventricle and reduced the potency of the alpha-adrenoceptor antagonists in vas deferens only slightly. Treatment of right ventricular strips with CdCl2 markedly reduced resting tension and enhanced maximal inotropic effects of isoprenaline but did not affect its potency. 3. Inactivation of cardiac alpha 1B-adrenoceptors by treatment with chloroethylclonidine slightly enhanced the maximal inotropic effects of the full agonist, adrenaline and of several partial agonists. 4. Schild analysis of inhibition experiments with the alpha 1A-adrenoceptor-selective antagonists, 5-methyl-urapidil and (+/-)-tamsulosin, demonstrated that adrenaline causes its inotropic effects mainly via the alpha 1B-adrenoceptor subtype. Schild analysis of 5-methyl-urapidil inhibition experiments in chloroethylclonidine-treated ventricles indicated that only alpha 1A-adrenoceptors mediate the inotropic effects of adrenaline following inactivation of the alpha 1B-adrenoceptors. 5. In control ventricles the organic Ca2+ entry blocker, nitrendipine and treatment with the inorganic Ca2+ entry blocker, CdCl2 did not reduce inotropic effects of adrenaline whereas ryanodine treatment inhibited them. In contrast, nitrendipine and CdCl2 treatment had major inhibitory effects in chloroethylclonidine-treated but lacked inhibitory effects in phenoxybenzamine-treated ventricular strips. 6. We conclude that inotropic effects of adrenaline in rat heart are mediated mainly by alpha 1B-adrenoceptors via release of Ca2+ from an intracellular pool. Following inactivation of alpha 1B-adrenoceptors by chloroethylclonidine treatment, alpha lA-adrenoceptors can fully compensate and mediate inotropic effects by promoting influx of extracellular Ca2+ at least partly via voltage-operated channels.Therefore, we speculate that alpha 1B-adrenoceptors exert a tonic inhibitory effect on alpha 1A-adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗

Corticosterone modulates interleukin-evoked fever in the rat.

The role of endogenous corticoids in fever responses caused by recombinant murine interleukin (IL)-1 beta and IL-6 was studied in adult male Wistar rats. Adrenalectomy diminished the development of fever after intracerebroventricular (icv) injection of these ILs and lowered body temperature. Intraperitoneal administration of the same doses of ILs did not produce fever in intact animals or hypothermia in adrenalectomized rats, thus suggesting a central site of action of IL-1 beta and IL-6 in these experiments. Chronic replacement with moderate doses of corticosterone restored the fever response in adrenalectomized animals in response to icv administration of IL-1 beta but only partially reversed the fever caused by IL-6. Adrenalectomized animals acutely treated with corticosterone and thereafter with either IL-1 beta or IL-6 developed fever more rapidly than did chronically corticosterone-treated animals. In intact animals corticosterone blocked the fever response to icv injected IL-1 beta. We propose that in the rat corticosterone acts in a bimodal manner on body temperature; it exerts a permissive central effect on the fever response and limits the production of inflammatory mediators in the brain. Conversely, higher corticosterone doses probably reduce the magnitude of the fever response.

Adrenalectomy↗

[Effect of intravenous glucose versus glucose-xylose (1:1) administration on carbohydrate and lipid metabolism after trauma and during infection].

OBJECTIVE: To detect the effects of glucose-xylitol infusion versus glucose infusion alone on carbohydrate and lipid metabolism in postoperative stress and during sepsis. DESIGN: Prospective randomized study (study I after cardiac surgery) and intraindividual cross-over control study (study II in septic patients), respectively. SETTING: Intensive care unit of a university hospital. PATIENTS: 18 patients after aortocoronary bypass (ACVB) and 5 patients with sepsis. INTERVENTIONS: In study I during the first 24 postoperative hours one group (K I, n = 6) received glucose only (2 mg/kg BW/min), a second group (K II, n = 6) a mixture of glucose and xylitol (1:1; 2 mg/kg BW/min) and a third group (K III, n = 6) a glucose-containing electrolyte solution (0.8 mg/kg BW/min). Glucose, lactate, insulin and free fatty acid concentrations were measured pre- and postoperatively in 6-hour intervals over 36 h. In study II patients were firstly given 4 mg glucose/kg BW/min over 6 h, then infusion was changed to a 1:1 glucose-xylitol mixture (4 mg/kg BW/min) for another 6 h. Hepatic glucose production, palmitate oxidation rates and lactate concentrations were determined at the end of both infusion regimens. RESULTS: Glucose and insulin concentrations were significantly lower in K II and K III than in K I. The highest lactate values were observed 6 h postoperatively in K I. Concentrations of all fatty acids were lower in K I than in K II and K III during the infusion periods. In study II the glucose production and lactate values were significantly reduced during xylitol infusion, whereas palmitate oxidation rates were significantly increased when the infusion regimen changed from glucose to glucose-xylitol mixture. CONCLUSIONS: These data indicate that energetically ineffective high glucose concentrations were avoided and lactate production was diminished by infusion of glucose-xylitol in study I. In addition, xylitol achieved a higher endogenous release and oxidative utilisation of free fatty acids representing important fuel substrates after trauma and during sepsis.

Adult↗

Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor gamma chain.

To expand the spectrum of recognition of effector lymphocytes and to redirect them towards predefined targets, we have altered the specificity of human tumor-infiltrating lymphocytes (TIL) through stable modification with chimeric receptor genes consisting of single-chain antibody variable regions linked to the gamma subunit common to the immunoglobulin (Ig)G and IgE Fc receptors. Using either hapten or ovarian carcinoma-specific monoclonal antibodies, we constructed chimeric receptor genes and retrovirally introduced them into CD8+ TIL. Redirected TIL specifically lysed trinitrophenyl-labeled Daudi or a human ovarian carcinoma cell line (IGROV-1), and secreted granulocyte/macrophage colony-stimulating factor upon stimulation with the appropriate antigen. This strategy may allow new approaches towards the adoptive immunotherapy of cancer in humans.

Cloning, Molecular↗