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Biomedical subjects

S C Gilman

Publications and source records attributed to S C Gilman.

At least 37 records · Page 2Linked to original sources
PubMed1992

Frequent anti-V-region immune response to mouse B72.3 monoclonal antibody.

The immune response of 56 colorectal cancer patients to a single infusion of 1 mg of radiolabeled (111In) mouse B72.3-GYK-DTPA immunoconjugate was examined using a double-antigen radiometric assay system. The incidence of antibody response was 48% to polyclonal mouse IgG, 71% to mouse B72.3, and 62% to chimeric B72.3. Twelve patients (23%) had an antibody response to B72.3 V region in the absence of binding to polyclonal mouse IgG. An antiidiotype response was demonstrated in sera from 36% of 25 patients examined and correlated well with chimeric B72.3-GYK-DTPA immunoconjugate binding (r = 0.72, moderately well with mouse B72.3 binding (r = 0.56), and not at all with polyclonal mouse IgG binding (r = 0.28). The peak antibody response occurred most frequently 2 weeks postinfusion, although a "delayed" peak response to chimeric B72.2 occurred in 29% of patients. This study suggests that mouse B72.3 causes an immune response in the majority of patients and that antibody response to the V region is common. Understanding the physiological significance of these antibody responses will require correlation with the kinetics and tumor localization of repeat infusions of such immunoconjugates.

Animals↗
PubMed1992

Interaction studies of tilomisole, aspirin, and naproxen in acute and chronic inflammation with assessment of gastrointestinal irritancy in the rat.

The effect of combination NSAID therapy of tilomisole with aspirin or naproxen was studied in rats with carrageenan-induced paw edema and established adjuvant arthritis. Inflamed paws were measured using mercury plethysmography and the arthritic paws were X-rayed to determine any bony/soft tissue changes. The gastrointestinal tract was also examined for bleeding and ulceration. Tilomisole had a less potent acute anti-inflammatory effect than aspirin or naproxen, but produced no significant gastrointestinal damage. A significant reduction in anti-inflammatory activity was observed with the tilomisole/aspirin combination in acute inflammation. Only additive interactions were observed with the naproxen inhibition. In the established arthritis assay, a significant synergistic anti-inflammatory response, i.e. both inhibition of paw edema and bone erosion, was also observed with the 80 and 93% tilomisole/naproxen combinations. The gastric ulcerogenic effect of the combination paralleled its increased activity. The synergism between tilomisole and naproxen in this chronic arthritic model may be due to enhanced cyclooxygenase inhibitory activity. These drug interaction studies suggest possible interactions in human clinical trials of rheumatoid arthritis.

Animals↗
PubMed1992

Use of traditional and modern health services by Laotian refugees.

Although refugee health care emerged as a special interest in the United States following the influx of almost a million Southeast Asians since 1975, few studies have been done of the influence of refugee traditions on the use of Western medical services. The illness patterns, medical beliefs, and health care behavior of a Southeast Asian refugee group, the Mien from Laos are described in this study. A cohort of 119 Mien refugees living in Richmond, California, was observed for a 6-month period. In-home interviews were undertaken about all episodes of ill health, including treatment and health care decisions. This study shows that the Mien integrate traditional healing beliefs and practices with the use of American health services. Such findings are important because the increasing cultural diversity in the United States, particularly in Western states, necessitates that health care professionals understand the importance of cultural factors for access to and the use of health care by all patients including refugees and other immigrant groups.

Adolescent↗
PubMed1991

Immunohistochemical and pharmacokinetic characterization of site-specific immunoconjugate 15A8-glycyl-tyrosyl-(N-epsilon-diethylenetriamine pentaacetic acid)-lysine derived from anti-breast carcinoma monoclonal antibody 15A8.

In this study, the breast carcinoma-reactive monoclonal antibody 15A8 and a site-specific immunoconjugate of the antibody, 15A8-glycyl-tyrosyl-(N-epsilon-diethylenetriamine pentaacetic acid)-lysine (15A8-GYK-DTPA), were characterized by immunohistological methods for reactivity with normal and neoplastic human tissues and normal cynomolgus monkey tissues. In addition, 15A8-GYK-DTPA labeled with 111In was assessed by in vivo imaging and pharmacokinetic studies for localization to human tumor xenografts in nude mice. The native antibody and the site-specific immunoconjugate exhibited similar limited reactivity with normal human tissues. Specifically, epithelial structures, including normal breast epithelium, lung alveoli, bronchial epithelium and glands, liver bile ducts, pancreatic ducts, kidney distal and collecting tubules, epidermal and esophageal epithelium, endometrial glands, and thymic Hassall's corpuscles, were reactive. Normal monkey tissues stained with 15A8 exhibited a similar pattern of reactivities. Antibody 15A8 reacted broadly with epithelium-derived tumors; more than 60% of the cells in all of the breast, colon, non-small cell lung, ovarian, prostate, bladder, and renal carcinomas tested expressed the antigen. In contrast, a variety of nonepithelial neoplasms, including lymphomas, melanomas, sarcomas, and small cell lung carcinomas, were nonreactive. 15A8-GYK-DTPA-111In administered i.v. rapidly localized to and imaged both MX-1 and MCF-7 human breast carcinoma xenografts in nude mice, reaching maximal levels of about 20% of injected dose/g of tumor within 4 days. No unusual localization to any nontumor tissue or organ was seen; the level of radioactivity in the normal tissues and organs was at or below that seen in the blood. Furthermore, the immunoconjugate did not accumulate in xenografts of the antigen-negative breast carcinoma ZR-75-1, which indicates that tumor localization was antigen specific. Pharmacokinetic studies in cynomolgus monkeys suggested that significant amounts of 15A8-GYK-DTPA-111In did not localize to normal epithelia and demonstrated that the immunoconjugate was not toxic. These findings suggest that antibody 15A8 may be useful in the diagnosis and therapy of breast cancer and possibly other carcinomas.

Animals↗
PubMed1991

Interaction of Ca-channel blockers and high pressure at the crustacean neuromuscular junction.

Exposure to high pressure causes a significant depression of synaptic transmission. We examined the effects of various Ca-channel blockers and their interaction with high pressure on excitatory neuromuscular junction currents (EJCs) of lobster abdominal muscles. Reduced [Ca2+]o to half of normal concentration or exposure to 40-60 microM CdCl2, 10-20 microM NiCl2 and 1 microM omega-conotoxin decreased EJCs by 50%. Nifedipine, Nitrendipine and Bay K-8644 were ineffective. Either Ca-blockers or reduced [Ca2+]o, enhanced EJC suppression exerted by high pressure. The data suggest that high pressure primarily affects Ca2+ inflow at the presynaptic terminals through N-type voltage-gated Ca-channel.

Animals↗
PubMed1991

A 23187-stimulated calcium uptake and GABA release by cerebrocortical synaptosomes: effects of high pressure.

Guinea pig cerebrocortical synaptosome preparations were used to study the effect of compression to 62 ATA on 45Ca2+ uptake and [3H]GABA release using a calcium ionophore A 23187, which bypasses the voltage-sensitive calcium channel. Pressure was found to exert a suppressive effect on the A 23187-induced release of [3H]GABA, while having no significant effect on A 23187-stimulated 45Ca2+ uptake. On the other hand, both depolarization-induced 45Ca2+ uptake and [3H]GABA release were inhibited by pressure exposure. These results suggest that pressure may suppress GABA release by affecting pre-synaptic events subsequent to calcium influx.

Animals↗
PubMed1991

Antitumor monoclonal antibodies generated by immunization with mucins.

This report describes the development and characterization of monoclonal antibody EG2.3. Although produced from a fusion that used splenocytes from donor mice immune to bovine salivary mucin (BSM), EG2.3 bound selectively to a number of human tumor cell lines including colon adenocarcinoma LS174T. Therefore, EG2.3 was compared to B72.3, another mucin (TAG-72) binding monoclonal antibody that also binds to LS174T. Like B72.3, EG2.3 reacted with an epitope on TAG-72. However, these two MAbs differed in a number of ways. Treatment of mucin or TAG-72 with periodate did not reduce the binding of EG2.3 to either antigen. In contrast, B72.3 did not react with either periodate treated antigens. Removal of sialic acid from either BSM or TAG-72 compromised the reactivity of both EG2.3 and B72.3. It was concluded that the EG2.3 binding site was distinct from the carbohydrate structure detected by B72.3.

Animals↗
PubMed1990

Immunohistochemical and pharmacokinetic characterization of the site-specific immunoconjugate CYT-356 derived from antiprostate monoclonal antibody 7E11-C5.

In this study, a site-specific immunoconjugate, designated CYT-356, of the prostate-reactive monoclonal antibody 7E11-C5 was characterized by immunohistological methods for reactivity with normal and neoplastic human tissues. In addition, CYT-356 labeled with 111In was assessed by in vivo imaging and pharmacokinetic studies for localization to human tumor xenografts in nude mice. The native antibody and the site-specific immunoconjugate exhibited similar patterns of reactivity with normal human tissues. Although the majority of tissues tested were negative, weak reactivity with cardiac muscle, proximal kidney tubules, and sweat glands was observed. Positive staining of normal prostate epithelial cells and glandular lumina and strong reactivity with a subset of skeletal muscle cells were also observed. CYT-356 reacted with 100% of prostate tumors examined but was negative on a variety of other neoplasms. Following i.v. administration, CYT-356-111In rapidly localized to and imaged LNCaP human prostate adenocarcinoma xenografts in nude mice, reaching maximal levels of about 30% of injected dose/g of tumor within 3 days. No unusual localization was seen to any nontumor tissue or organ; the level of radioactivity in the normal tissues and organs was at or below that seen in the blood. The localization to xenografts was antigen specific and the accessible binding sites in 100-200-mg tumors appeared to be saturated at an antibody dose between 10 and 100 micrograms. These findings suggest that the CYT-356 immunoconjugate may be useful in the diagnosis and therapy of prostate cancer.

Animals↗
PubMed1990

Carbohydrate-derivatized immunoconjugate of the anti-(carcinoembryonic antigen) monoclonal antibody C46: immunohistological reactivity and pharmacokinetic comparison with a randomly derivatized C46 immunoconjugate.

In this study, a site-specific glycyl-tyrosyl-(N-epsilon-diethylenetriaminepentaacetic acid)-lysine (GYK-DTPA) immunoconjugate of the anti-carcinoembryonic antigen monoclonal antibody C46 (C46-GYK-DTPA) was characterized by immunohistological and immunofluorescence methods for reactivity with normal and neoplastic human tissues. In addition, pharmacokinetic studies assessed the ability of C46-GYK-DTPA labeled with 111In to localize to and image human tumor xenografts in nude mice. The native antibody and the site-specific immunoconjugate exhibited similar patterns of reactivity with normal human tissues. C46 did not bind to the surface of normal human granulocytes, which indicates lack of reactivity with normal cross-reacting antigen. C46-GYK-DTPA reacted with 100% of the colon, breast and renal carcinomas examined and with two of three lung carcinomas, but did not react with any sarcomas, melanomas or lymphomas examined. Intravenously administered C46-GYK-DTPA-111In rapidly localized to and imaged LS174T human colon adenocarcinoma xenografts in nude mice, reaching maximal levels of about 25% of injected dose/g tumor within 1 day. No unusual localization to any non-tumor tissue or organ was seen; the level of radioactivity in the normal tissues and organs was at or below that in the blood. The accessible binding sites in 1 g tumors appeared to be saturated at an antibody dose between 100 micrograms and 1000 micrograms/mouse. Further, in a direct in vivo comparison, the site-specific conjugate C46-GYK-DTPA had more favorable pharmacokinetics and better tumor localization than a randomly derivatized C46 immunoconjugate (C46-DTPA). These findings suggest that the site-specific immunoconjugate C46-GYK-DTPA may be useful in the diagnosis and therapy of colon cancer and other adenocarcinomas expressing carcinoembryonic antigen.

Animals↗
PubMed1990

Effect of helium and heliox on glutamate decarboxylase activity.

The activity of glutamate decarboxylase (GAD) in pure helium at 6.8 MPa was significantly enhanced when compared to GAD activity in air at 0.1 MPa (906 vs. 602 nmol.h-1.mg-1 protein, respectively). No significant difference was found between GAD activities in heliox at 6.8 MPa (0.87% O2 at 6.8 MPa) and in air at 0.1 MPa. On the other hand, the activities in heliox at 0.1 MPa (0.87% O2 at 0.1 MPa) and air at 0.1 MPa were significantly different (655 and 446 nmol.h-1.mg-1 protein, respectively). These data indicate that pressures up to 6.8 MPa do not affect the GAD-catalyzed synthesis of gamma-aminobutyric acid, but that the enzyme, as previously reported, is sensitive to low levels of oxygen.

Animals↗
PubMed1990

Characterization of interleukin 1 induced rabbit chondrocyte phospholipase A2.

Stimulation of rabbit articular chondrocytes with interleukin 1 (IL-1) results in the activation of intracellular phospholipase A2 (PLA2) and the subsequent secretion of this enzyme into the extracellular milieu. Pretreatment of chondrocytes with actinomycin D or cycloheximide significantly inhibited IL-1 induced PLA2 activation and secretion, suggesting that the enzyme induction process is RNA and protein synthesis dependent. Chondrocyte PLA2 is highly calcium dependent with a 1 mM optimum CA++ concentration for hydrolytic activity; little or no hydrolysis is observed in the absence of calcium and the hydrolytic activity is abolished in the presence of 10 mM ethylenediamine tetraacetic acid. The enzyme is also pH sensitive with optimal PLA2 hydrolytic activity observed at pH 6.5-7. Further, chondrocyte PLA2 was sensitive to inhibition by mepacrine, a compound with PLA2 inhibitory activity. The IL-1 induced chondrocyte PLA2 has a molecular weight of approximately 10 kDa, as determined by molecular sieve G75 column chromatography. The apparent molecular weight and CA++, pH and drug sensitivity of the extracellular and intracellular forms of the IL-1 induced chondrocyte PLA2 are indistinguishable. Since this IL-1 induced enzyme has similar biochemical characteristics to PLA2 enzymes isolated from human rheumatoid and osteoarthritic synovial fluid, we suggest that the chondrocyte may be an important cellular source for this PLA2 enzymatic activity in inflamed joints.

Animals↗
PubMed1989

Development and characterization of monoclonal antibodies with specificity for metallic radioisotope chelators linked to antibodies and other proteins.

Monoclonal antibodies with specificity for the diethylenetriaminepentaacetic acid (DTPA) portion of the GYK-DTPA (glycyl-tyrosyl-lysine-DTPA) linker structure used to chelate metals to immunoglobulins have been prepared. A significant proportion of these antibodies were lambda light chain isotype. Competition assays demonstrated that DTPA, rather than GYK, was the binding site of the antibodies tested. These monoclonal antibodies should be useful reagents for use in assays specific for the presence of the common linker structure used to chelate metallic radioisotopes to monoclonal antibodies. The antibodies tested did not discriminate between chelated and unchelated DTPA.

Amino Acid Sequence↗
PubMed1989

Alterations in brain monoamine neurotransmitter release at high pressure.

High pressure exposure produces neurological changes which manifest as tremors, EEG changes and convulsions. Since previous studies have implicated the involvement of the monoaminergic system in these symptoms, it was of interest to study monoamine release at high pressure. Synaptosomes isolated from guinea pig brain were used to follow monoamine efflux at 68 ATA. The major observation was a decrease in the initial calcium dependent release of all three monoamines in response to K+ induced depolarization. This response is similar to that previously observed for GABA, glycine and glutamate. This generalized pressure induced depression of initial transmitter release suggests a mechanism common to the release process for both excitatory and inhibitory neurotransmission.

Animals↗
PubMed1989

Pressure-dependent changes in the release of GABA by cerebrocortical synaptosomes.

Previous studies describe a depression in potassium-evoked, calcium-dependent transmitter release from guinea pig cerebrocortical synaptosomes in response to compression to 68 ATA with heliox. The study described in this paper was designed to evaluate whether a similar effect could be detected at lower pressures and to determine whether the effect had an abrupt onset with a fixed response or a progressive response varying over a range of pressures. A typical response to potassium-evoked depolarization was observed at all pressures studied. This consisted of an initial rising phase lasting 2 to 3 min followed by a falling phase. There was a pressure-dependent depression in the absolute amount of transmitter released as well as a depression in the rate of release in the first minute following stimulation. The mean depression in gamma-aminobutyric acid release during the first minute was an average of 15% at 19 ATA, 28% at 37 ATA, 38% at 50 ATA, and 54% at 62 ATA when compared to a 1 ATA control.

Animals↗
PubMed1988

Interleukin-1 activates phospholipase A2 in human synovial cells.

Interleukin-1 (IL-1) treatment of synovial cells from rheumatoid arthritis and osteoarthritis patients resulted in a dose-dependent secretion of phospholipase A2 (PLA2). IL-1 also stimulated prostaglandin E2 and plasminogen activator synthesis, in parallel with PLA2 activation; all 3 were detectable within 6 hours of IL-1 treatment and peaked by 24 hours. Synovial cell PLA2 required calcium (5 mM) and a neutral pH (7.5) for maximal activity and appears similar to the PLA2 in synovial fluid, which has been described previously. We conclude that PLA2 can be induced by IL-1, and its secretion may contribute significantly to the inflammatory actions of IL-1.

Arthritis, Rheumatoid↗
PubMed1988

Pressure suppresses serotonin release by guinea pig striatal synaptosomes.

Exposure to high pressure produces neurologic changes in humans which manifest as tremor, EEG changes, and convulsions. Since previous studies have implicated the involvement of the serotoninergic system in these symptoms, it was of interest to study serotonin release at high pressure. Synaptosomes isolated from guinea pig striatum were used to follow serotonin efflux at 68 ATA. The major observation was a decrease in [3H]serotonin release from depolarized striatal synaptosomes at 68 ATA. In view of the role of serotonin as an inhibitory neurotransmitter in this area, the observed decrease in synaptic release leads us to conclude that decreased serotoninergic activity in striatal neurons probably is contributing to the hyperexcitability associated with HPNS.

Animals↗
PubMed1988

Release of dopamine from striatal synaptosomes: high pressure effects.

Adverse neurological manifestations of exposure to high hydrostatic pressure include tremor and convulsions, suggesting an alteration in synaptic transmission, particularly with inhibitory pathways. Because striatal transmission has been implicated in the high pressure neurologic syndrome (HPNS), we investigated the effect of pressure exposure on the release of a major inhibitory neurotransmitter in this region. Synaptosomes isolated from the guinea pig striatum were used to study the effect of compression to 67.7 ATA on [3H]dopamine release. Pressure was found to have a suppressive effect on the initial release of [3H]dopamine by synaptosomes isolated from the striatum of guinea pigs. This finding suggests that decreased inhibitory regulation at the level of the striatum contributes to the hyperexcitability associated with compression to high pressure.

Animals↗