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Biomedical subjects

G Gross

Publications and source records attributed to G Gross.

At least 19 recordsLinked to original sources

[Carbohydrate and lipid metabolism following heart bypass operations. The effect of the intravenous hypocaloric administration of glucose versus glucose xylitol (1:1)].

The effect of glucose-xylitol infusion on carbohydrate and lipid metabolism was investigated in 18 metabolically normal men (mean age 56.1 [35-65] years) with coronary heart disease after they had undergone a coronary artery bypass operation. During the first postoperative hours, group I (n = 6) received glucose only (2 mg/kg.min), group II (n = 6) glucose+xylitol (1 mg/kg.min each), and group II a glucose-containing electrolyte solution (0.83 mg/kg.min glucose). Blood glucose and insulin concentrations during the infusion period were significantly (P < 0.05) lower in groups II and III than I (glucose after 6 h: group I 21.5 [15.3-26.8] mmol/l; group II 14.2 [11.2-18.1] mmol/l; group III 12.6 [6.8-16.0] mmol/l). The highest lactate concentrations were reached in group I, 6 hours after the operation. Palmitine and stearine, as well as oleic and linoleic acid concentrations were significantly lower 12 hours postoperatively in group I than groups II and III (P < 0.05). These data indicate that energy-ineffective high glucose concentrations were avoided and endogenous lactate production reduced by the postoperative infusion of glucose+xylitol. In addition, it achieved a higher supply of free fatty acids as energy source to the myocardium without reaching toxic concentrations in the postischaemic myocardium.

Adult

Bilateral rupture of the patellar tendon without predisposing systemic disease.

Bilateral rupture of the patellar ligament in a 49-year-old woman is reported. She sustained a relatively minor trauma and no underlying systemic disease could be found. This is the 14th case of simultaneous spontaneous rupture of the patellar tendons reported in the literature. The diagnostic features were diffuse swelling around the knees, visible and palpable infrapatellar defects, and an inability to extent either leg.

Female

Platelet-derived growth factor isoforms AA, AB, and BB differentially activate poly r(I):r(C)-induced genes in human fibroblast FS4 cells.

Polyribocytidylic-polyriboinosinic acid [poly r(I):r(C)]-inducible genes were isolated by a differential screening procedure from a human fibroblast cell (FS-4) cDNA bank. Among yet unidentified genes (gene 274), one codes for a protein with multiple finger motifs and has previously been detected in endothelial cells after tumor necrosis factor-alpha (TNF-alpha) treatment (A20; Opipari et al., 1990), the second one codes for a variant of the I kappa B family (Haskill et al., 1991), and a third one for the Ca2+ ATPase (isoform 1). Platelet-derived growth factor (PDGF) isoforms (AA, AB, and BB) stimulated the expression of these immediate-early genes. But the extent of the respective induction correlated neither with the number of the two receptors alpha or beta nor with the level of PDGF-stimulated receptor autophosphorylation on tyrosine. Although alpha-receptors were less abundant than beta-receptors (12,500 binding sites were estimated for PDGF-AA, KD 0.03 nM; 20,000 for PDGF-AB, KD 0.03 nM; 35,000 for PDGF-BB KD 0.16 nM) and tyrosine phosphorylation induced by PDGF-AA was significantly less than that evoked by PDGF-BB, some of the investigated genes were more strongly induced by PDGF-AA. We discuss how the differences in the biological potency of the PDGF isoforms may reside in different functions of the two receptors by activation of alternative signaling pathways.

Base Sequence

Endowing T cells with antibody specificity using chimeric T cell receptors.

T cells recognize antigen in the form of a peptide associated with a cell surface molecule encoded by the major histocompatibility gene complex (MHC). The elaborate requirements for the T cell receptor (TCR)-antigen interaction stand in contrast to the simple and defined nature of the antigenic determinants recognized by antibodies. The similarity in the molecular structure and gene organization between antibodies and the TCR has prompted attempts to interchange the antigen-binding, variable regions of these molecules. To this end, chimeric TCR (cTCR) genes, composed of the variable domains of antibodies linked to TCR constant regions, have been used to confer antibody-type specificity on T cells. cTCR-expressing T cells respond to stimulator cells as well as to immobilized antigen in an MHC unrestricted and independent manner. The antibody-like specificity of the resulting T cells has been exploited, using defined ligands, to elucidate the physicochemical parameters that govern TCR-mediated signaling, and to provide a useful experimental system to study the role of MHC and cell-adhesion/accessory molecules in T cell activation. The successful expression of such cTCR in transgenic mice opens new avenues to explore the role of the MHC in T cell development and maturation. Eventually, chimeric receptors specific to tumor or viral antigens might be used for in vivo targeting of T cells in the framework of immuno- and gene therapy.

Animals

Biliary complications related to laparoscopic cholecystectomies: radiologic diagnosis and management.

The purpose of this study was to review the radiologic presentations and management of biliary complications related to laparoscopic cholecystectomies. Additionally, a computed tomography (CT) evaluation of asymptomatic postsurgical patients was performed to determine the uncomplicated appearance of the gallbladder fossa. Over a 24-month period 23 biliary complications were seen in patients who underwent laparoscopic cholecystectomies (group 1). Twenty asymptomatic patients were examined with unenhanced CT examinations after laparoscopic cholecystectomy (group 2). Twenty patients in group I had bilomas located in the gallbladder fossa (n = 9), subhepatic (n = 7) and subphrenic (n = 2) spaces, and diffusely distributed in the peritoneal cavity (n = 2). The bile leaks were presumed to have been proved to be from the cystic duct (n = 19), right hepatic duct (n = 1), and common bile duct n = 3) injuries and leaks. Fourteen drains were placed percutaneously using CT (n = 12) or sonographic (n = 2) guidance, and in two cases drains were placed surgically. The duration of catheter drainage average 11.3 days. Six patients underwent endoscopic retrograde cholangiopancreatography (ERCP) procedures, including sphincterotomy (n = 6) and stent placement (n = 3). Patients who were treated with a drain or ERCP procedures or who were managed conservatively all recovered without the need for additional surgery. In five cases, the bile cultures were positive for multiple organisms. Three patients underwent surgical repairs for disrupted common bile ducts. In group 2 CT examinations showed minimal fluid densities in all patients. No evidence of distinct, well-demarcated fluid collection was seen in any of the 20 patients. (ABSTRACT TRUNCATED AT 250 WORDS)

Bile

Functional assembly of chimeric T-cell receptor chains.

We have generated cytotoxic T-cell hybridomas expressing chimeric T-cell receptors (cTCR) with an antibody-type specificity for the TNP hapten. Transfectants expressing the cTCR genes could mediate specific lysis of haptenated tumor cell lines of various types and secrete IL-2 upon stimulation with TNP modified cells. In a previous report, we showed that double-gene transfectants expressing either VHC alpha and VLC beta or VHC beta and VLC alpha could be activated by TNP-modified stimulator cells or TNP proteins immobilized on plastic. Single-chain transfectants (expressing VHC alpha or VHC beta alone) could be mainly activated by TNP-cells. We now report that transfection of chimeric VHC alpha gene into an alpha-chain-defective mutant restores the surface expression of the TCR/CD3 complex. In parallel, such transfectants regained the ability to respond to mitogen and anti-CD3 antibodies and responded weakly to TNP cells. Double gene transfectants, bearing 2 complementary chimeric chains, expressed high amounts of cTCR on their surface, sufficient to acquire sound anti-TNP reactivity. Cells expressing the VHC beta gene only were not functional and had no detectable surface TCR chains. Taken together, our results suggest that chimeric VHC alpha chains can pair with endogenous V beta C beta chains, but that there is preferential association between complementary chimeric chains, resulting in higher functional expression of the chimeric TCR.

Animals

[Risks and benefits of thrombendarterectomy in bilateral internal carotid artery stenosis].

Among the patients who were operated for cerebrovascular insufficiency, one third suffered from bilateral stenoses of the internal carotid artery. In a retrospective analysis of 47 patients who were operated in consecution and of 28 patients who refused operation and were treated conservatively, the outcome was compared to cases with a one-sided stenosis. 31 patients were operated on one side and 16 on both sides. 28 of the surgically treated cases were followed up for an average of 32 months. The morbidity of 3.2% of the bilateral cases was twice as high as that of the unilateral cases. A permanent neurological deficit was observed in 2 patients after reconstruction of the asymptomatic but higher grading stenosis, but in none of the 18 cases after reconstruction of the symptomatic side although the stenosis of the other side was not removed. Patients with bilateral stenoses of the internal carotid artery should therefore be operated first on the symptomatic side. The frequently concomitant coronary artery disease of these patients prevents an improvement of the survival period in the group of bilaterally operated patients. The success in these cases concerns only the quality of life. The risk of a subsequent stroke in the 28 not operated cases with bilateral stenoses was 14.6% and therefore much higher than in the group of operated patients. Increase of the stenoses during the observation period is a prognostically unfavorable sign. Low dose treatment with platelet aggregation inhibitors (less than 500 mg ASS) increased the risk of an apoplectic insult.

Carotid Artery, Internal

[Condylomata acuminata in childhood--pointing to sexual abuse].

The cause of condylomata acuminata and of other anogenitally located HPV lesions in children often remains undetermined. Sexual abuse is a possible cause of HPV infection in childhood. Non-venereal transmission of HPV, such as autoinoculation and heteroinoculation from extragenital sites to genitalia, however, is much more likely in this age group. Histology and HPV typing of genital warts may provide evidence for non-venereal transmission of HPV in children. Identification of the genital HPV types HPV 6, 11, 16, 18, 31, etc. in a child is no proof of sexual abuse. Behavioural abnormalities and a carefully elicited history aid clinicians in coming to reliable conclusions and in deciding whether an HPV infection in a child is sexually transmitted and due to sexual abuse.

Child

RNase E cleavage in the atpE leader region of atpE/interferon-beta hybrid transcripts in Escherichia coli causes enhanced rates of mRNA decay.

Chimeric transcripts containing the ribosome binding site of the Escherichia coli atpE gene and variants of the human structural interferon-beta gene are subject to RNase E processing in the 5'-untranslated atpE part of the transcripts. The absence of processing at two sites in the atpE leader-sequence caused by the RNase E deficiency in E. coli host N3431 leads to a considerable stabilization of the mRNA moiety. RNase E has originally been described as a processing enzyme for non-mRNAs such as precursor 5 S rRNA and RNA1, but cleavage mRNA substrates have also been reported. RNase E processing of the atpE gene leader sequence-containing transcripts leads to an increased rate of mRNA breakdown. The two RNase E-dependent processing sites in the atpE part of the mRNA transcripts exhibit some similarity to the other known RNase E processing sites. The influence of RNase E cleavage upon post-transcriptional regulation such as RNA stability and the efficiency of translational initiation is discussed.

Bacteriophage lambda

Serotonin release in the rat brain cortex is inhibited by neuropeptide Y but not affected by ACTH1-24, angiotensin II, bradykinin and delta-sleep-inducing peptide.

The effects of neuropeptide Y (NPY), peptide YY (PYY), pancreatic polypeptide and of another four peptides on the electrically evoked 3H overflow were studied in superfused rat brain cortex slices preincubated with 3H-serotonin. In addition, we determined the effect of NPY on the Ca2(+)-induced 3H overflow from rat brain cortex slices and synaptosomes (preincubated with 3H-serotonin) and on the forskolin-stimulated accumulation of cAMP in a membrane fraction from rat brain cortex. The electrically (3 Hz) evoked 3H overflow was inhibited by PYY, NPY and pancreatic polypeptide (decreasing order of potency), but not affected by ACTH1-24, angiotensin II, bradykinin and delta-sleep-inducing peptide. The inhibitory effect of NPY did not change when the stimulation frequency was lowered to 1 Hz, but was markedly reduced at 10 Hz. The inhibitory effect of a presumably maximally active concentration of PYY was not altered in the presence of NPY or pancreatic polypeptide (effects not additive), whereas the inhibition produced by a maximally active concentration of the alpha 2-adrenoceptor agonist clonidine was further increased by NPY. NPY also inhibited (1) the tritium overflow, evoked by introduction of Ca2+, in slices superfused with Ca2(+)-free and K(+)-rich medium containing tetrodotoxin, (2) the tritium overflow, evoked by simultaneously increasing Ca2+ and K+ in the superfusion fluid of synaptosomes previously superfused with Ca2(+)-free medium and (3) the forskolin-stimulated accumulation of cAMP in rat brain cortex membranes. The present results suggest that NPY inhibits serotonin release in the rat brain via presynaptic NPY receptors, which are also activated by PYY and pancreatic polypeptide and may be negatively coupled to an adenylate cyclase.

Adenylyl Cyclases

[Initial experiences with a new monoclonal antibody in diagnosis of malignant melanomas].

In a study of 17 patients with malignant melanomas in the extremities the sensitivity and specificity of a new monoclonal antibody directed at melanoma cells (BW 575, Behring) were investigated. The specificity was 100%, but the sensitivity 70%. In 3 cases known foci could not be detected. All nodular melanomas and their metastases were detected (9 patients). Repeated examination during the first 24 h after injection of the Tc-99m-marked antibody, and two-plane investigations made it possible to detect even small tumors less than 1 cm in diameter and subcutaneous lesions where the melanomas absorbed the antibodies. Due to its high specificity, the antibody seems to be a promising aid in deciding the operative strategy.

Adult

Trimipramine: pharmacological reevaluation and comparison with clozapine.

Trimipramine has been reported to differ from other typical tricyclic antidepressant drugs in several aspects, for instance it does not inhibit neuronal transmitter uptake and does not cause down-regulation of beta-adrenoceptors. Moreover, it may possess antipsychotic activity in schizophrenic patients. In the present investigation it was found that trimipramine did not alter the electrically-induced release of [3H]noradrenaline and [3H]5-hydroxytryptamine, from slices of the cerebral cortex of the rat, in concentrations of less than 1 microM. It did not antagonize the inhibitory effect of noradrenaline and 5-hydroxytryptamine on the release of transmitter, mediated by presynaptic autoreceptors. In radioligand binding studies, D,L-trimipramine showed fairly high affinities (KI 10-60 nM) for some dopamine (DA), noradrenaline and 5-hydroxytryptamine (5-HT) receptor subtypes (5-HT2 receptors = alpha 1A/B-adrenoceptors greater than or equal to D2 receptors), intermediate affinities (300-550 nM) for D1 receptors, alpha 2B-adrenoceptors and 5-HT1C receptors but only low affinities (greater than 1000 nM) for alpha 2A-adrenoceptors, 5-HT1A, 5-HT1D and 5-HT3 receptors. It may thus be classified as an atypical neuroleptic drug. Especially, its affinities for dopamine receptors, alpha 1-adrenoceptors and 5-HT2 receptors closely resembled the values measured for clozapine. The L-enantiomer of trimipramine showed higher affinities for these binding sites than D-trimipramine. The present findings may explain the mechanism of the potential antipsychotic action but not the antidepressant effect of trimipramine.

Animals

Regional and laminar distributions of alpha 1-adrenoceptors and their subtypes in human and rat hippocampus.

The distributions of the alpha 1-adrenoceptor and its subtypes (alpha 1A and alpha 1B) in human and rat hippocampus are analysed by quantitative receptor autoradiography. alpha 1-Adrenoceptors are labelled by [3H]prazosin. The alpha 1A subtype is visualized by [3H]prazosin after irreversible blockade of alpha 1B adrenoceptors with chloroethylclonidine or directly by [3H]5-methyl-urapidil. The alpha 1B subtype is investigated by [3H]prazosin binding in the presence of the alpha 1A antagonist 5-methyl-urapidil. Considerable differences in the regional and laminar patterns of alpha 1-adrenoceptors are found between rat and human hippocampi. The rat hippocampus is characterized by a low overall density and a rather homogeneous regional and laminar distribution. This is in contrast to the human pattern, which shows a much higher overall level of alpha 1 receptor density and a restriction of alpha 1 receptors to the CA3 region of Ammon's horn and the dentate gyrus. Moreover, alpha 1A and alpha 1B receptors of the human hippocampus are differentially distributed with the alpha 1A subtype concentrated in the hilus and lucidum layer of CA3, and the alpha 1B subtype concentrated in the molecular layer of the dentate gyrus. Additionally, the distribution of alpha 1 receptors is compared with the distribution of 5-hydroxytryptamine 1A receptors. The subtype specific pattern is correlated with the distribution of glutamatergic systems in the human (but not in the rat) hippocampus. alpha 1A Receptor localization coincides with the target area of the mossy fibre system, and alpha 1B receptors are preferentially localized in the target area of the hippocampal associational fibres and partly of the perforant pathway. This result points to possible interactions between noradrenaline- and glutamate-mediated neurotransmission differentiated by topographically segregated alpha 1-adrenoceptor subtypes.

Adrenergic alpha-Antagonists

Quantitative autoradiography of 11 different transmitter binding sites in the basal forebrain region of the rat--evidence of heterogeneity in distribution patterns.

The distribution of 12 different binding sites for acetylcholine, L-glutamate, GABA, 5-hydroxytryptamine, dopamine and noradrenaline was measured with quantitative receptor autoradiography in four regions of the rat basal forebrain (medial septal nucleus including vertical and horizontal limbs of the diagonal band of Broca, magnocellular preoptic nucleus, substantia innominata and basal nucleus of Meynert, ventral pallidum). L-Glutamate binding sites represent the largest portion of the analysed receptors in all regions, followed by muscarinic2, 5-hydroxytryptamine1 and GABAA receptors. Muscarinic1, dopamine1, dopamine2 and 5-hydroxytryptamine2 receptors and alpha 1-, alpha 1A- and alpha 1B-adrenoceptors represent the minor receptor populations. The largest portion of the dopamine receptors is represented by the dopamine1 subtype, and the alpha 1B subtype dominates the alpha 1-adrenoceptor group. A heterogeneity of the distribution patterns of the different receptors throughout the basal forebrain regions is found. A comparison of the patterns shows that alpha 1-adrenoceptors have a similar regional distribution to that of the muscarinic2 receptors, but both receptor types have reciprocal distributions compared with the 5-hydroxytryptamine1 receptors. The results indicate that one transmitter may exert different effects in the basal forebrain regions depending on the densities of the respective receptor subtypes. Moreover, similar or reciprocal distribution patterns of some, but not all, analysed receptors point to a non-random association (co-distribution) of the different transmitter systems in the basal forebrain regions.

Animals

Compliance testing of reusable containers for transport of type A packages of radioactive material.

Transporting radioactive materials within a medical complex comes under jurisdiction of the U.S. Department of Transportation when public highways are used. A strong, reusable container to safely transport radioactive material was developed and tested at Mayo Medical Center to satisfy the requirements of the U.S. Department of Transportation and Nuclear Regulatory Commission. The container successfully completed water spray, free drop, compression, and penetration tests. It has been in use for 3 y without any loss of radioactive materials.

Drug Packaging

Genital warts do not respond to systemic recombinant interferon alfa-2a treatment during cannabis consumption.

The case of a 22-year-old man suffering from genital warts is described. The lesions responded completely to recombinant interferon alfa-2a only after discontinuation of cannabis consumption. Cannabis was detected using the enzyme immunoassay/1-trans-tetrahydrocannabinoid method in urine. Southern blotting of frozen genital wart biopsy material revealed papillomavirus type 11 DNA, the amount of which increased significantly during interferon treatment. The final clearing of lesions after discontinuation of cannabis consumption implicates that the drug-induced impairment of cellular immunity was reversible. It is concluded that drug abuse and especially cannabis consumption may play some role in the world-wide increase in genital papillomavirus disease and in the high number of recalcitrant courses of genital warts.

Adult