Biomedical subjects

G Gross

Publications and source records attributed to G Gross.

At least 127 records · Page 7Linked to original sources

PubMed1993

Tissue- and subunit-specific regulation of G-protein expression by hypo- and hyperthyroidism.

Thyroid hormone status has profound effects on signal transduction in various tissues throughout the body. Therefore, we quantified the signal transducing G-proteins in the rat heart, cerebral cortex, vas deferens and liver by immunoblotting and pertussis toxin labeling in response to chemically induced hypothyroidism (treatment with propylthiouracil) and hyperthyroidism (treatment with triiodothyronine). Levels of the pertussis toxin (PTX) substrates Gi alpha and Go alpha in the heart and vas deferens were inversely correlated with thyroid hormone levels, i.e. Gi alpha and Go alpha were decreased or unchanged in hyperthyroid rats and increased in hypothyroid rats compared to control animals. The cerebral cortex and liver expression of PTX substrates Gi alpha and Go alpha was not affected by changes in thyroid hormone. Regulation of Gs alpha protein was more complex in that Gs alpha was unaffected in the other tissues tested. Expression of G-protein beta-subunits was not affected by thyroid status in the heart, liver, or cerebral cortex. Our results suggest that tissue- and G-protein-specific factors are involved in the regulation of G-protein subunits by thyroid hormone. Moreover, cardiac expression of Gs alpha is upregulated by increases or decreases in the normal level of thyroid hormone.

Animals↗

PubMed1993

Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors.

The generation of tumor-specific lymphocytes and their use in adoptive immunotherapy is limited to a few malignancies because most spontaneous tumors are very weak or not at all immunogenic. On the other hand, many anti-tumor antibodies have been described which bind tumor-associated antigens shared among tumors of the same histology. Combining the variable regions (Fv) of an antibody with the constant regions of the T-cell receptor (TCR) chains results in chimeric genes endowing T lymphocytes with antibody-type specificity, potentially allowing cellular adoptive immunotherapy against types of tumors not previously possible. To generalize and extend this approach to additional lymphocyte-activating molecules, we designed and constructed chimeric genes composed of a single-chain Fv domain (scFv) of an antibody linked with gamma or zeta chains, the common signal-transducing subunits of the immunoglobulin receptor and the TCR. Such chimeric genes containing the Fv region of an anti-trinitophenyl antibody could be expressed as functional surface receptors in a cytolytic T-cell hybridoma. They triggered interleukin 2 secretion upon encountering antigen and mediated non-major-histocompatibility-complex-restricted hapten-specific target cell lysis. Such chimeric receptors can be exploited to provide T cells and other effector lymphocytes, such as natural killer cells, with antibody-type recognition directly coupled to cellular activation.

Animals↗

PubMed1993

Rapid measurement of blood leakage during regional chemotherapy.

In order to avoid complications after regional chemotherapy (isolated hyperthermic perfusion) of the extremities, rapid measurement of blood leakage from the extracorporeal to the systemic circulation is important. A method using technetium-99m in vivo red blood cell (RBC) labelling is reported that provides results within 3 min. Blood samples drawn from the systemic and the extracorporeal circulation were measured for 99mTc activity using a mobile well counter, and the leakage values calculated. The mean result was 7.6% +/- 6.5%/15 min (n = 209). The corresponding flow rate was 100.2 +/- 85.7 ml/15 min (mean +/- SD). The values for isolation perfusion of the upper and the lower extremities are compared. The leakage results using 99mTc RBC labelling were correlated with other blood pool markers. Iodine-125 human serum albumin and indium-113 m transferrin were administered in subgroups of 4 and 19 patients simultaneously. Using linear regression, the coefficient of correlation was 0.72 for 99mTc/113mIn and 0.58 for 99mTc/125I. Comparison with the alternatives suggests that the rapid method of leakage measurement after 99mTc RBC labelling can be considered one of the most practicable and reliable methods available.

Chemotherapy, Cancer, Regional Perfusion↗

PubMed1993

Hyperdopaminergia in schizophreniform psychosis: a chronobiological study.

Circadian rhythm abnormalities have been described in various psychiatric disorders, but they have not received much attention in studies of schizophrenia and schizophreniform psychosis. The present study used the cosine model to determine the circadian patterns of amino acids, dopamine, and prolactin concentrations, which were analyzed over a 24-hour period in serum of healthy subjects, drug-free schizophrenic patients, and neuroleptic-treated schizophrenic patients. The mesor (the daily mean) of phenylalanine was lower in drug-free schizophrenic women than in healthy women. The mesors of the ratio of phenylalanine or tyrosine to competing amino acids were similar in healthy subjects and patients. The ratio of phenylalanine/competing amino acids showed a phase advance (i.e., earlier onset of the time of highest concentration) in drug-free patients compared with healthy subjects. Schizophrenic patients displayed a higher dopamine mesor than healthy subjects. Female drug-free schizophrenic patients had lower prolactin mesors and lower amplitudes (i.e., half of the total predictable change in rhythm) than healthy women. Compared with healthy subjects, schizophrenic patients showed a phase advance of circadian prolactin concentrations. Neuroleptics raised the prolactin mesor and amplitudes but did not elicit any phase change in amino acids, dopamine, or prolactin. These data confirm the indirect pharmacologic evidence of increased dopaminergic activity in schizophrenic patients that relates to dopamine's precursors and to the neuroendocrine regulation of prolactin.

Adolescent↗

PubMed1993

Expression of human bone morphogenetic proteins-2 or -4 in murine mesenchymal progenitor C3H10T1/2 cells induces differentiation into distinct mesenchymal cell lineages.

The cDNAs encoding the human bone morphogenetic proteins BMP-2 and BMP-4 in an eukaryotic expression vector were permanently transferred into the murine mesenchymal progenitor cell line C3H10T1/2. Originally, these cells are known to differentiate into myotubes, adipocytes, and chondrocytes upon the addition of azacytidine. Permanent transfection of genes encoding human BMP-2 and BMP-4 induces differentiation into the osteogenic lineage. The osteogenic differentiation potential of C3H10T1/2 cells is substantiated by histochemical and genetic analyses of marker genes typical or specific for osteogenesis, including the parathyroid hormone receptor, alkaline phosphatase, osteopontin, osteonectin, and osteocalcin. In addition to osteoblast formation, development into adipocytes and chondrocytes is also observed, suggesting that BMP-2 and BMP-4 induce differentiation into three mesenchymal lineages.

Adipocytes↗

PubMed1993

Purification and chemical characterization of beta-trace protein from human cerebrospinal fluid: its identification as prostaglandin D synthase.

beta-Trace protein from pooled human CSF was purified to homogeneity. An apparent molecular mass of 23-29 kDa was determined for the polypeptide on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Amino-terminal sequencing of the polypeptide yielded the unique amino acid sequence APEAQVSVQPNFQQDKFLGRWFSA. Alignment of amino acid sequences obtained from tryptic peptides with the sequence previously deduced from a cDNA clone isolated by other investigators allowed the identification of beta-trace protein as prostaglandin D synthase [prostaglandin-H2 D-isomerase; (5Z, 13E)-(15S)-9 alpha, 11 alpha-epidioxy-15-hydroxyprosta-5,13-dienoate D-isomerase; EC 5.3.99.2]. A conservative amino acid exchange (Thr instead of Ser) was detected at amino acid position 154 of the beta-trace polypeptide chain in the corresponding tryptic peptide. The two N-glycosylation sites of the polypeptide were shown to be almost quantitatively occupied by carbohydrate. Carbohydrate compositional as well as methylation analysis indicated that Asn29 and Asn56 bear exclusively complex-type oligosaccharide structures (partially sialylated with alpha 2-3- and/or alpha 2-6-linked N-acetylneuraminic acid) that are almost quantitatively alpha 1-6 fucosylated at the proximal N-acetylglucosamine; approximately 70% of these molecules contain a bisecting N-acetylglucosamine. Agalacto structures as well as those with a peripheral fucose are also present.

Amino Acid Sequence↗

PubMed1993

Effects of maternal deprivation on the ACTH stress response in the infant rat.

Prolonged maternal deprivation during early ontogeny results in increased basal and stress-induced corticosterone levels. In the following experiments we examined whether these increases were due, at least in part, to augmented ACTH secretion. Thus, ACTH levels were measured in 24-hour maternally deprived and nondeprived 6-, 9-, and 12-day-old pups exposed to a mild stressor (i.e. saline injection followed by placement in a novel environment at room temperature). The results showed: (1) nondeprived pups showed a small response to saline--the response of deprived pups, however, was greater than that of nondeprived pups; (2) the magnitude of the response increased with age; (3) ACTH levels remained elevated for at least 30 min. Subsequent experiments examined whether the continuous exposure to novelty and/or loss of body heat could explain the persistence of this response. Neither variable affected the ACTH response to saline. Our results indicate that factors of maternal origin are partly responsible for the regulation of the ACTH response to stress. Furthermore, the persistence of the response suggests that the negative feedback system in the infant is immature.

Adrenocorticotropic Hormone↗

PubMed1993

[Human papillomaviruses. Associated diseases of the breast].

In human papillomavirus-associated acanthomas of the mamilla it was possible to detect DNA of HPV types 41, 6ma and a type related to type 16. The biology of HPV infection resembles that of anogenital lesions. Some of the HPV types found are rare or are thought possibly to have oncogenic potency. Possible evidence for link between HPV and carcinomas of the breast is discussed.

Adolescent↗

PubMed1993

Anti-leucocyte function-associated antigen-1 antibodies inhibit T-cell activation following low-avidity and adhesion-independent interactions.

Anti-leucocyte function-associated antigen-1 (LFA-1) antibodies can provide either stimulatory or inhibitory signals to T cells, depending on the epitope they recognize, type and stage of activation of the T cells, and nature of the activation stimulus. Because of the low affinity of interaction between the T-cell receptor (TcR) and the antigen/major histocompatibility complex (MHC), it was proposed that the LFA-1 molecule strengthens the adhesion between the interacting cells, thus contributing in an additive manner to TcR-specific interactions. To check if high-avidity, TcR-specific interactions still require the accessory function of the adhesion molecule, we studied the effect of anti-LFA-1 antibodies on T-cell triggering mediated through chimeric receptors composed of an Fv of an antibody and a constant region of the TcR. Such chimeric TcR (cTcR) confer on T cells antibody-type specificity and affinity. We made use of transfected T-cell hybridomas expressing various amounts of either one cTcR chain (composed of VH linked to C beta) or double-chain cTcR (VHC beta + VLC alpha). When such transfectants were stimulated with hapten-modified cells, anti-LFA-1 antibodies inhibited activation predominantly mediated through cTcR composed of a single chimeric chain and did not inhibit stimulation of the double-chain transfectants. Moreover, these anti-LFA-1 antibodies blocked antigen-specific T-cell activation regardless of whether the stimulus was adhesion dependent or not, such as in the case of stimulation by immobilized hapten-protein conjugates. These studies show that the 'off-signal' provided by anti-LFA-1 antibodies is adhesion independent and affects mainly low-avidity TcR-antigen interactions.

Animals↗

PubMed1993

[Cardiocirculatory side effects of hyperthermic extremity perfusion].

The risk of cardiocirculatory disorders was investigated in 23 consecutive patients with high-risk melanomas, who had been treated with hyperthermal limb perfusion. Postoperatively, there was a rise in the pulmonary vascular resistance. In addition, 14 patients with vascular occlusive diseases (1-2b, Fontaine) showed intraoperatively an increasing amount of leakage of the extracorporeal circulation. Elevations of thromboxane and prostacyclin in excess of the norm caused by mechanical and thermic traumatization of blood in the heart lung machine were detected in 8 patients investigated during and after the perfusion procedure. Significant increase of cisplatin, one of the two cytostatic agents injected extracorporeally, could not be demonstrated in the blood of the systemic circulation by atomic absorption spectroscopy. Increased pulmonary and arterial pressure disorders were observed in the group with occlusive vascular diseases, caused by a rising rate of vascular collaterals to the body and the rising rate of thromboxane and prostacyclin in the body blood flow. We believe that it is necessary to monitor pulmonary arterial pressure during isolated limb perfusion, especially in patients with vascular occlusive disease.

Adult↗

PubMed1993

[Osteosynthesis using a buttress plate--a new principle for stabilizing scaphoid pseudarthroses].

Deformity with palmar bone resorption can be observed in 20-50% of scaphoid pseudarthroses. A palmar wedge-shaped defect develops after repositioning and debridement of the pseudarthrosis. In the present paper 16 cases in which operations with cancellous bone grafting and palmar buttress plate osteosynthesis in addition were performed are presented. In all but 1, the pseudarthrosis united. All patients were pain-free at follow-up examination a minimum of 9 months (mean 28 months) only slightly reduced. Grip strength and mobility were after operation. The persisting pseudarthrosis necessitated wrist arthrodesis because of radiocarpal arthrosis. Metal slackening with erosion and rupture of the flexor pollicis longus tendon occurred in 1 patient. Palmar buttress plating is a biomechanically consistent form of osteosynthesis. It neutralizes all relevant forces. This means that cancellous bone grafts are sufficient, whereas lag screw or tension band osteosyntheses need cortico-cancellous grafts to resist compression forces. Stability and better chances of healing of pure cancellous bone grafts are the main advantages of palmar buttress plating in scaphoid pseudarthroses.

Bone Plates↗

PubMed1992

[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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

[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↗