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Biomedical subjects

J Unger

Publications and source records attributed to J Unger.

At least 37 records · Page 2Linked to original sources
PubMed1997

Comparison of patient characteristics and outcome between a single-institution phase II trial and a cooperative-group phase II trial with identical eligibility in metastatic melanoma.

Differences in overall survival and response rates are often noted when promising single-institution phase II treatment regimens are evaluated in a cooperative group setting. One reason for this discrepancy may be the differences in patient characteristics at the time of registration. In the metastatic melanoma literature, the prognostic factors for survival that are most frequently identified are the number of metastatic sites, visceral involvement, performance status, liver involvement, and possibly the disease-free interval and gender. A prognostic factor for response appears to be sites of involvement. A comparison of patient characteristics and outcome was conducted for patients entered in similar phase II melanoma trials at a single institution versus those in a cooperative group. Sixty-four patients at Wayne State University (WSU) were compared with 96 patients who had nearly identical eligibility criteria and were registered in the Southwest Oncology Group (SWOG). All patients were receiving comparable phase II treatments for metastatic melanoma. Southwest Oncology Group patients were significantly older (p < 0.001), had worse performance status (p = 0.03), had more visceral involvement (p = 0.001), and were more likely to have two or more metastatic sites (p = 0.02). No significant differences in gender (p = 0.55), absence or presence of liver involvement (p = 0.12), or disease-free interval were noted. These disparities, despite similar eligibility, may partly explain the observed differences in survival (WSU median = 10 months, SWOG median = 7 months; p = 0.13) and response rates (WSU = 31%, SWOG = 15%; p = 0.02) between the two groups of patients. Investigators should report these important patient characteristics in treatment reports. These differences highlight the difficulty in comparing single-institution and cooperative-group phase II trials, even with comparable patient eligibility. This serves to emphasize the need for well-designed phase III trials when comparing treatment approaches and stratification for the prognostic factors identified.

Adult↗
PubMed1997

Characterization of Fc epsilonRI expressing human monocytic cell lines. 1. The role of CD45 on signal transduction in primary monocytes and cell lines.

BACKGROUND: Recently, the high affinity receptor for IgE (Fc epsilonRI), which plays a major role in allergies, has been identified on a number of different antigen-presenting cell types, including human monocytes from atopic and nonatopic donors. In this report human monocytic cell lines were used to test for the expression of Fc epsilonRI, reasoning that a monocytic cell line expressing Fc epsilonRI constitutively would be a useful tool for large scale studies on the regulation of IgE binding and signal transduction. METHODS: Reverse transduction polymerase chain reaction was applied to identify Fc epsilonRI alpha-chain message, flow cytometry to detect Fc epsilonRI surface expression and signal transduction on the cell lines generated by transfection. RESULTS: We report the establishment of monocytic cell lines constitutively expressing Fc epsilonRI (THP1-alpha01 to THP1-alpha40) generated by transfection of the cell line THP1 with a plasmid encoding the Fc epsilonRI alpha-chain only. Fc epsilonRI on the THP1-alpha lines specifically binds IgE and is functional with regard to ligand binding and signal transduction. Comparative studies between the transfectants and primary human monocytes from nonatopic donors demonstrated the regulatory role of the tyrosine phosphatase CD45 on Fc epsilonRI-mediated cell activation. CONCLUSIONS: Monocytic cell lines carry Fc epsilonRI alpha-chain RNA and enhancement by transfection results in surface Fc epsilonRI expression on THP1. Triggering the receptor on the THP1-alpha lines or on human monocytes, which express native Fc epsilonRI, elicits a rapid and transient calcium mobilization, prevented by co-cross-linking of Fc epsilonRI and CD45.

Calcium↗
PubMed1996

[Endogenously formed nitric oxide in nasal mucosa of the human: detection by nicotinamide-adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry].

BACKGROUND: Nitric oxide (NO) is an intercellular transmitter, both in the central and in the peripheral nervous system. In addition to nerve cells, NO is also produced in epithelial cells of various tissues and in the endothelium. NO is formed by the action of nitric oxide synthase (NOS). There is evidence that NOS can be marked by NADPH-diaphorase (NADPH-d) activity in many cell types. The aim of this study was to identify NOS-positive structures in human nasal mucosa by using NADPH-d-histochemistry. METHODS: Frozen sections from inferior turbinates were fixed with buffered formalin and then treated according to the description of Vincent and Kimura. Additionally, the same sections underwent a double staining procedure for acetylcholinesterase (Karnovski-Roots) to show a correlation with cholinergic nerve structures. RESULTS: Strong reactions were found in the epithelium and in nerve fibres, compared to less NADPH-d activity in seromucous glands and the endothelium of the different vessel types. Singular NADPH-d positive nerves were found within nerve bundles, periarterially, in the subepithelial layer and surrounding glands and their ducts. A frequent localisation of NADPH-d could be detected in parasympathetic nerve fibres. CONCLUSIONS: The occurrence of NADPH-d in epithelial, glandular and nerval structures suggests that NOS takes part in physiological functions and possible pathophysiological processes of the nose. Similar to findings in various other organs this investigation demonstrated that the neurotransmitter NO can also be associated with the parasympathetic nervous system in the human nasal mucosa.

Acetylcholinesterase↗
PubMed1996

Strontium-89 chloride (Metastron) for palliative treatment of bony metastases. The University of Minnesota experience.

Strontium-89 chloride (Metastron) is an FDA-approved treatment for palliation of cancer pain. We evaluated blood count changes and pain relief in 28 patients with widespread painful bony metastasis treated with strontium-89 at the University of Minnesota Hospital and Clinics. Eighteen patients had prostate cancer (all hormone-refractory cancer), seven patients had breast cancer, and three patients had lung cancer, all previously treated with either radiation, chemotherapy, or a combination of the two. Serial blood counts were performed weekly up to 8 weeks and at 12 weeks after administering Metastron. Pain scale and blood values were monitored simultaneously. The mean baselines of hemoglobin (Hgb), white blood count (WBC), and platelets (Plts) were 11.4, 5900, and 258,000, respectively. The mean dose of Metastron was 3 mCi (range 2.2-4.4). The median time (range) to nadir was about 6 weeks. The percentage reductions relative to baseline were 32% (range 0-72%) for WBC; 14% (range 0-50%) for Hgb; 15% (range 0-47%) for the red blood cell (RBC) count; and 40% (range 0-85%)for Plts. We did not find a close relationship among the baseline blood count, reduction of subsequent blood counts, or previously irradiated active bone marrow volume. The median time of survival was 23 weeks (range 2-66 weeks). At 12 weeks, 29% of patients had moderate to dramatic improvement of pain, 32% had some relief of pain, and 50% had no improvement in pain. Thirty-two percent of the treated patients required additional palliative external beam radiation to their bony lesions within the study period. Our results show that Metastron for palliation for bony metastases should be used with caution because of moderate to severe bone marrow toxicity, especially in platelets, associated with its use. Careful evaluation of patients given Metastron is needed to assess accurately its full benefit.

Adult↗
PubMed1996

Basic innervation pattern and distribution of classic autonomic neurotransmitters in human nasal mucosal vasculature.

The neural control of human nasal vasculature is still not completely understood. This study was performed to demonstrate the innervation pattern of the different vessel types and to distinguish between nor-adrenergic and cholinergic structures. General innervation was demonstrated using antibodies to neuron-specific enolase and S-100 protein. Autonomic structures were shown by using antibodies to tyrosine hydroxylase and choline acetyltransferase (ChAT). In addition, choline acetyltransferase (AChe) histochemistry was performed. Nasal vasculature is controlled by a dense innervation that increases with the thickness of the tunica media. While all larger vessels show a mixed autonomic innervation, sympathetic structures seem to predominate in veins. These findings demonstrate that classic neurotransmitters play a major role in the regulation of nasal vasculature. The stronger innervation of arteries and cushion veins underlines their central position in the control of nasal air flow.

Adrenergic Fibers↗
PubMed1996

Fibromyalgia.

Explore the source record for details and available documents.

Female↗
PubMed1996

[Amiodarone and thyroid: pharmacologic and toxic effects].

Amiodarone increases free T4, decreases free T3 and transiently increases TSH, that sometimes becomes undetectable. Amiodarone may induce: a) hypothyroidism, diagnosed by low free T4 and treated by l-thyroxine; b) thyrotoxicosis, diagnosed by high total or free T3, and some times requiring perchlorate, corticoids, plasmapheresis and thyroidectomy. Dysthyroidism is excluded by a normal TSH level, controlled twice a year.

Amiodarone↗
PubMed1995

Three dimensional planning target volumes: a model and a software tool.

PURPOSE: Three dimensional (3D) target volumes are an essential component of conformal therapy because the goal is to shape the treatment volume to the target volume. The planning target volume (PTV) is defined by ICRU 50 as the clinical target volume (CTV) plus a margin to ensure that the CTV receives the prescribed dose. The margin must include all interfractional and intrafractional treatment variations. This paper describes a software tool that automatically generates 3D PTVs from CTVs for lung cancers and immobile head and neck cancers. METHODS AND MATERIALS: Values for the interfractional and intrafractional treatment variations were determined by a literature review and by targeted interviews with physicians. The software tool is written in Common LISP and conforms to the specifications for shareable software of the Radiotherapy Treatment Planning Tools Collaborative Working Group. RESULTS: The tool is a rule-based expert system in which the inputs are the CTV contours, critical structure contours, and qualitative information about the specific patient. The output is PTV contours, which are a cylindrical expansion of the CTV. A model for creating PTVs from CTVs is embedded in the tool. The interfractional variation of setup uncertainty and the intrafractional variations of movement of the CTV (e.g., respiration) and patient motion are included in the model. Measured data for the component variations is consistent with modeling the components as independent samples from 3D Gaussian distributions. The components are combined using multivariate normal statistics to yield the cylindrical expansion factors. Rules are used to represent the values of the components for certain patient conditions (e.g., setup uncertainty for a head and neck patient immobilized in a mask). The tool uses a rule interpreter to combine qualitative information about a specific patient with rules representing the value of the components and to enter the appropriate component values for that patient into the cylindrical expansion formula. CONCLUSION: The portable software tool allows the rapid, consistent, and automatic generation of 3D PTVs from CTVs.

Head and Neck Neoplasms↗
PubMed1995

Plasma platelet-activating factor acetylhydrolase is a secreted phospholipase A2 with a catalytic triad.

Platelet-activating factor (PAF) is a potent pro-inflammatory autacoid with diverse physiological and pathological actions. These actions are modulated by PAF acetylhydrolase, which hydrolyzes the sn-2 ester bond to yield the biologically inactive lyso-PAF. In contrast to most secreted phospholipase A2s, plasma PAF acetylhydrolase is calcium-dependent and contains a GXSXG motif that is characteristic of the neutral lipases and serine esterases. In this study we tested whether the serine in this motif is part of the active site of plasma PAF acetylhydrolase and, if so, what the other components of the active site are. Using site-directed mutagenesis, we demonstrated that Ser-273 (of the GXSXG motif), Asp-296, and His-351 are essential for catalysis. These residues were conserved in PAF acetylhydrolase sequences isolated from bovine, dog, mouse, and chicken. The linear orientation and spacing of these catalytic residues are consistent with the alpha/beta hydrolase conformation of other lipases and esterases. In support of this model, analysis of systematic truncations of PAF acetylhydrolase revealed that deletions beyond 54 amino acids from the NH2 terminus and 21 from the COOH terminus resulted in a loss of enzyme activity. These observations demonstrate that although plasma PAF acetylhydrolase is a phospholipase A2 it has structural properties characteristic of the neutral lipases and esterases.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1995

[Current immunohistochemical results of localization of vasoactive intestinal polypeptide (VIP) in nasal mucosa of the human].

Besides classic neurotransmitters, neuropeptides seem to participate in the control of human nasal physiology. In this region vasoactive intestinal peptide (VIP) is found in higher concentration than other neuropeptides. The aim of this study was to localize VIP in neuronal and non-neuronal structures of the human nasal mucosa using immunocytochemical techniques. Paraffin and frozen serial sections of the inferior turbinate were incubated with antibodies against neuronspecific enolase (NSE) to demonstrate neuronal structures or against VIP. The immunocomplexes were visualized by the Avidin-Biotin-Complex (ABC)-method. VIP-positive nerve fibers were found around the acinus cells and the ducts of the seromucous glands. These results emphasize the influence of VIP on nasal gland secretion. Few immunoreactions to the VIP were demonstrated in the nerves of the adventitia of veins and arteries. Additionally, by comparing NSE nad VIP localization, strong extranerval immunoreactions in the tunica medica of the arterioles were demonstrated, as were lesser but still visible immunoreactions in the muscular layer of thick veins. These morphological findings in vessels and the well known vasodilatory effect of VIP underline the functions of this neuropeptide on the nasal mucosa in man. Thus, by increasing the blood flow and volume, VIP, in conjunction with other control factors, seems to participate in the physiological processes of the swelling mechanism of nasal turbinates and influence nasal congestion.

Adult↗
PubMed1995

Explaining exercise behavior and satisfaction with social exchange theory.

This study tested the hypothesis that the variables specified by social exchange theory (perceived rewards of exercising, perceived costs of exercising, social and tangible investments, and available alternative activities) are associated with exercise behavior and satisfaction. 190 health club members completed a questionnaire assessing attitudes toward exercise, exercise behavior, and demographic information. Exercise frequency and satisfaction were regressed on the social exchange theory variables and demographic covariates. Exercise satisfaction, the number of investments in exercise, and the number of available alternative activities were significantly related to exercise frequency, and the number of perceived rewards of exercise and the number of investments were significantly related to exercise satisfaction. These results suggest that social exchange theory is useful for explaining exercise behavior.

Adult↗
PubMed1995

[Immunohistochemical studies of the occurrence of "calcitonin gene-related peptide" (CGRP) in nasal mucosa of the human].

In addition to classic neurotransmitters, neuropeptides are believed to regulate functions of the nasal mucosa in man. The aim of this study was to localize the vasoactive neurotransmitter calcitonin gene-related peptide (CGRP) in different mucosal structures by immunocytochemical methods. Frozen sections of the inferior turbinates from 12 patients were incubated with antibodies to CGRP and immunocomplexes were visualized by the ABC (Avidin-Biotin-Complex) method. CGRP-positive nerve fibers were demonstrated in the adventitia of arteries and arterioles. Immunoreactions were also found in interstitial spaces and around ducts of seromucous glands. Additional immunoreactions were detectable in subepithelial nerves and mast cells. These morphologic findings indicate that CGRP may participate in the transmission of sensory stimuli, in vasoregulation and in allergic reactions. The occurrence of CGRP in the different anatomic structures suggests multiple roles of this neuropeptide in the nasal mucosa of man.

Adult↗
PubMed1994

Amino acid metabolism by hepatocytes in a hybrid liver support bioreactor.

The amino acid patterns of medium perfusate in a liver cell bioreactor developed for a hybrid liver support system have been measured. There were considerable changes in the concentrations of glutamic acid, glutamine, alanine, arginine, ornithine and branched chain amino acids during the first 10 days which is indicative of dynamic cellular metabolism. From day 15, steady state conditions of nitrogen metabolism are reflected by stable amino acid turnover. Monitoring of urea, K+, and P-450 activity suggests that hepatocytes have switched to a stable protein synthesis with a general amino acid uptake and keto acid release following cell volume increase.

Amino Acids↗
PubMed1994

Alpha-keto acid metabolism by hepatocytes cultured in a hybrid liver support bioreactor.

Isolated pig liver cells cultured using a perfusion technique were analyzed over 39 days to test their ability to change the perfusate alpha-keto acid profile. While the pyruvate concentration in the culture medium decreased as of the first day, the alpha-ketoglutarate (KG), alpha-ketoisocaproate (KIC), alpha-ketoisovalerate (KIV) and alpha-keto-beta-methyl-n-valerate (KMV) were synthesized immediately and released by the liver cells. The metabolic capacity of the cell culture system increased up to day 10, decreased during the following 5 days and reached a steady state beyond day 15, which was maintained for at least 30 days. The branched chain alpha-keto acid release, in particular alpha-ketoisocaproate, reflects an effective transamination capacity of the newly developed culture system and shows an intact protein biosynthesis for at least 30 days in vitro.

Animals↗
PubMed1993

Opposite effects of intranigral ibotenic acid and 6-hydroxydopamine on motor behavior and on striatal neuropeptide Y neurons.

Unilateral lesions of the basal ganglia circuit induce a disequilibrium of motor processing, most obviously expressed by the resulting circling behavior. Compensatory events, which reduce the motor asymmetry, could be accompanied by changes in neurotransmitter/modulator parameters in the involved brain regions. In the present investigation, the effects of an interruption of the striato-nigro-thalamic loop by ibotenic acid (IBO)-induced lesions of total substantia nigra (SN) on circling behavior and on striatal neuropeptide Y (NPY) neurons were compared with those after the selective destruction of the dopaminergic nigrostriatal projection with 6-hydroxydopamine (6-OHDA). Directly after the operation, IBO-lesioned rats showed a high circling rate to the side contralateral to the lesion, whereas 6-OHDA-lesioned rats showed ipsiversive circling. With the lesion-induced development of dopamine receptor supersensitivity, 6-OHDA-treated rats, when stimulated with the dopaminergic agonist apomorphine, change their circling direction to the contralateral side. Complete IBO lesions of the SN abolished this effect: rats continued to circle to the contralateral side. These observations suggest that not only the dopaminergic denervation of the striatum but also the imbalance in the activity of the thalamo-cortical projection (reduced after 6-OHDA, augmented after IBO) are instrumental in determining the degree and direction of circling. Quantification of NPY-immunoreactive neurons in striatum revealed a decrease in 6-OHDA lesioned rats after 3 days on the side contralateral to the lesion, an effect even more pronounced after 4 month's survival time. IBO-induced lesions of the SN had an opposite effect on NPY-immunoreactivity in the striatum: neuron counts were lower on the ipsi- than on the contralateral side. In addition, a time-dependent variation in total number of NPY-neurons was noted: during the early postoperative periods an increase, followed by a prolonged decrease to values below 50% of the controls after 4 months. Taken together, these results provide evidence that a dopaminergic deafferentation and its consequences on the nigro-thalamo-cortical loop will determine NPY expression in the striatal interneurons. In particular, it is suggested that the number of striatal NPY-neurons and the imbalance in cortical activity are tightly coupled in terms of a negative correlation.

Animals↗