Search PubMed⌕ Search

Biomedical subjects

J B Mitchell

Publications and source records attributed to J B Mitchell.

At least 199 records · Page 11Linked to original sources
PubMed1991

Photodynamic therapy of the canine peritoneum: normal tissue response to intraperitoneal and intravenous photofrin followed by 630 nm light.

A toxicity study was performed in a canine model to explore the feasibility of using intraperitoneal photodynamic therapy for patients with peritoneal carcinomatosis. Dogs received 1.25 mg/kg Photofrin II both intravenously (48 hours) and intraperitoneally (2 hours) before intraperitoneal light treatment. The entire peritoneal surface was illuminated with 0.57-0.74 J/cm2 of red light (630 nm). Thirteen dogs were treated: 4 control and 9 full treatment. Of the fully treated dogs, 5 received a single treatment and 4 received 3 treatments. The dogs were evaluated clinically and pathologically for immediate (4 days) and late (60 days) side effects. All animals tolerated the treatment without significant morbidity. Postoperative blood tests were normal except for low lymphocyte counts and elevated liver transaminases, both of which normalized rapidly. Histopathologically, there was approximately a 50% incidence of mild inflammatory peritoneal response. This study provides the basis for a Phase I human trial.

Animals↗
PubMed1991

The role of anaerobic ability in middle distance running performance.

The purpose of this study was to assess the relationship between anaerobic ability and middle distance running performance. Ten runners of similar performance capacities (5 km times: 16.72, SE 0.2 min) were examined during 4 weeks of controlled training. The runners performed a battery of tests each week [maximum oxygen consumption (VO2max), vertical jump, and Margaria power run] and raced 5 km three times (weeks 1, 2, 4) on an indoor 200-m track (all subjects competing). Regression analysis revealed that the combination of time to exhaustion (TTE) during the VO2max test (r2 = 0.63) and measures from the Margaria power test (W.kg-1, r2 = 0.18; W, r2 = 0.05) accounted for 86% of the total variance in race times (P less than 0.05). Regression analysis demonstrated that TTE was influenced by both anaerobic ability [vertical jump, power (W.kg-1) and aerobic capacity (VO2max, ml.kg-1.min-1)]. These results indicate that the anaerobic systems influence middle distance performance in runners of similar abilities.

Adult↗
PubMed1991

Mn(III)-desferrioxamine superoxide dismutase-mimic: alternative modes of action.

Various low-molecular-weight copper chelates have been synthesized to mimic superoxide dismutase (SOD) by catalyzing O2-. dismutation. However, in the presence of cellular proteins, such chelates dissociate and thereby lose their SOD-mimetic activity. In contrast, desferrioxamine-Mn(III) 1:1 chelate (DF-Mn), an SOD-mimic that affords protection from oxidative damage, reportedly is stable in the presence of serum albumin. DF-Mn, unlike SOD, is reported to permeate the membrane of at least one cell type and can protect cells by detoxifying intracellular O2-.. Recently DF-Mn was shown to protect hypoxic cells from H2O2-induced damage. Such results suggest that DF-Mn can protect cells from O2-.-independent damage by alternative mechanisms. This study examines such possibilities. To avoid O2-. participation in the damaging process, killing of monolayered V79 Chinese hamster cells was induced in a hypoxic environment by t-butyl hydroperoxide (t-BHP). Damage induced by t-BHP was inhibitable by DF-Mn. DF-Mn was also found to rapidly oxidize iron(II)-bound DNA. Additionally, once DF-Mn oxidizes Fe(II) or Cu(I), the DF moiety of DF-Mn dissociates and rapidly binds to Fe(III) or Cu(II). Without excluding the possibility that DF-Mn protects cells by facilitating the removal of O2-., the present results show that this SOD-mimic can confer protection from cytotoxic processes independent of O2-. or of O2-.-derived active species.

Animals↗
PubMed1991

The effects of neonatal handling on the development of the adrenocortical response to stress: implications for neuropathology and cognitive deficits in later life.

Several years ago Levine, Denenberg, Weininger, Ader, and others described the effects of postnatal "handling" on the development of behavioral and endocrine responses to stress. The handling procedure usually involved removing rat pups from their cages, placing the animals together in small containers, and 15-20 min later, returning the animals to their cages and their mothers. The manipulation was performed daily for the first 21 days of life. As adults, handled (H) rats exhibited attenuated fearfulness (e.g., decreased freezing, increased exploration) in novel environments and a less pronounced increase in the secretion of adrenal glucocorticoids in response to a variety of stressors. These findings clearly demonstrated that the development of rudimentary, adaptive responses to stress could be modified by environmental events. We have followed on these earlier handling studies, convinced that this paradigm provides a marvelous opportunity to examine how subtle variations in the early environment alter the development of specific biochemical systems in the brain, leading to stable individual differences in biological responses to stimuli that threaten homeostasis. In this work we have shown how early handling influences the neurochemical development of certain brain regions that regulate the adrenocortical response to stress. Neonatal handling increases the efficiency of this endocrine response to stress, preventing excessive exposure to the highly catabolic adrenal steroids. In later life, this effect appears to protect the animal from potentially damaging effects of these steroids, ensuring the anatomical integrity of brain structures involved in cognitive functioning.

Adrenal Cortex↗
PubMed1991

Radiation sensitivity of human B-lineage lymphoid precursor cells.

We studied the radiation sensitivity of eight immunophenotypically distinct B-lineage lymphoid precursor cell (LPC) lines of acute lymphoblastic leukemia (ALL) or fetal liver origin corresponding to discrete developmental stages of human B-cell ontogeny. The radiation sensitivity of B-lineage LPC showed a temporal association with the distinct stages of development. FL112 and FL114 fetal liver pro-B cells (Stage 0 B-lineage LPC) with germline immunoglobulin heavy chain (IgH) genes but rearranged T-cell receptor gamma (T gamma) genes (DO of FL112 = 80.3 cGy, DO of FL114 = 50.2 cGy), REH ALL pre-pre-B cells (Stage I B-lineage LPC) with rearranged IgH and T gamma genes (DO = 66.1 cGy), and NALM-6 ALL pre-pre-B/pre-B cells (Stage II B-lineage LPC) (DO = 50.5 cGy) corresponding to the earliest three stages of human B-lymphocyte development were the most radiation sensitive B-lineage LPC populations. By comparison, KM-3 ALL pre-B (Stage III B-lineage LPC) (DO = 194.7 cGy), HPB-NULL ALL pre-B (Stage IV B-lineage LPC) (DO = 134.6 cGy), and sIgM+ RAJI/NAMALWA early B (Stage Va/b B-lineage LPC) cell lines (DO of RAJI = 144.0 cGy, DO of NAMALWA = 165.5 cGy) corresponding to the later stages of human B-lymphocyte development were much more radiation resistant. These results indicate that the radiation sensitivity of B-lineage LPC decreases during maturation within the B-lineage lymphoid precursor pathway. By comparison, the S-phase index (% of S-phase cells as determined by DNA flow cytometry) or proliferation index (% S + G2M), cellular protein content, intracellular glutathione (GSH) level, glutathione-S-transferase (GST) activity, intracellular pH, or free cytoplasmic calcium concentration did not correlate with the radiation sensitivity of the B-lineage LPC.

B-Lymphocytes↗
PubMed1991

Cellular mechanisms underlying the development and expression of individual differences in the hypothalamic-pituitary-adrenal stress response.

Several years ago Levine, Denenberg, Ader, and others described the effects of postnatal "handling" on the development of behavioral and endocrine responses to stress. As adults, handled rats exhibited attenuated fearfulness in novel environments and a less pronounced increase in the secretion of the adrenal glucocorticoids in response to a variety of stressors. These findings clearly demonstrated that the development of rudimentary, adaptive responses to stress could be modified by environmental events. We have followed these earlier studies, convinced that this paradigm provides a marvellous opportunity to examine how subtle variations in the early environment alter the development of specific neurochemical systems, leading to stable individual differences in biological responses to stimuli that threaten homeostasis. In this work we have shown how early handling influences the development of certain brain regions that regulate glucocorticoid negative-feedback inhibition over hypothalamic-pituitary-adrenal (HPA) activity. Specifically, handling increases glucocorticoid (type II corticosteroid) receptor density in the hippocampus and frontal cortex, enhancing the sensitivity of these structures to the negative-feedback effects of elevated circulating glucocorticoids, and increasing the efficacy of neural inhibition over ACTH secretion. These effects are reflected in the differential secretory pattern of ACTH and corticosterone in handled and nonhandled animals under conditions of stress. In more recent years, using a hippocampal cell culture system, we have provided evidence for the importance of serotonin-induced changes in cAMP levels in mediating the effect of postnatal handling on hippocampal glucocorticoid receptor density. The results of these studies are consistent with the idea that environmental events in early life can permanently alter glucocorticoid receptor gene expression in the hippocampus, providing evidence for a neural mechanism for the development of individual differences in HPA function.

Animals↗
PubMed1991

Effects of corticosterone on response consolidation and retrieval in the forced swim test.

In the forced swimming test, adrenal hormones regulate immobility time during a test swim given 24 hr after the initial training swim (e.g., the deficit in adrenalectomized animals is reduced when animals are given corticosterone [B] immediately after the training session). In this study, adrenalectomy decreased and B restored immobility during the test swims. The effects of adrenalectomy were completely reversed by 1 mg/kg doses of B, which results in plasma B levels that are comparable to values under basal resting conditions. Higher doses of B had no further effect. B given before or immediately after training partially reversed the effects of adrenalectomy. The complete reversal of the effects of adrenalectomy, however, required the presence of B during both training and testing, suggesting that B plays a role in the consolidation-retention and retrieval of the immobility response.

Adrenalectomy↗
PubMed1991

A light-diffusing device for intraoperative photodynamic therapy in the peritoneal or pleural cavity.

Light delivery to anatomic areas involved by tumor is critical for effective photodynamic therapy. The authors provide a detailed overview of a light-diffusing device which they have used for intraoperative illumination of the peritoneal and pleural cavities in patients with tumors involving the surfaces of these cavities. Their device represents an inexpensive modification of widely available endotracheal tubes. It has been used to deliver intraoperative photodynamic therapy in over 50 patients without episodes of device failure. When combined with a lipid-based, light-diffusing medium and on-line power/energy density monitoring, it allows homogeneous illumination of these complex surfaces.

Combined Modality Therapy↗
PubMed1991

Physician participation in Medicaid revisited.

Medicaid cut-backs during the Reagan Administration may have combined with other factors to affect physicians' willingness to participate in Medicaid. The author analyzed participation rates for two comparable groups of physicians: one group surveyed in 1977-78 and the other surveyed in 1984-85. Over this time period, there was a small, but statistically significant, decline in Medicaid participation rates (from 12.1-9.5%). Regression analysis showed, however, that physicians remain sensitive to important policy variables, such as fee levels and eligibility criteria. Physicians treat significantly more Medicaid patients when Medicaid fees are relatively high and when there is a relatively large number of people eligible for Medicaid in their area. These findings reinforce recent Congressional mandates to expand Medicaid eligibility and to raise payment levels for obstetric and pediatric services. Increased participation on the part of urban physicians, however, may be limited by the residential segregation of many Medicaid eligible people in the inner city.

Attitude of Health Personnel↗
PubMed1991

Nitroxide stable radicals protect beating cardiomyocytes against oxidative damage.

The protective effect of stable nitroxide radicals against oxidative damage was studied using cardiomyocyte cultures obtained from newborn rats. Monolayered cardiomyocytes were exposed to H2O2 and the effect on spontaneous beating and leakage of LDH was determined. Hydrogen peroxide irreversibly blocked rhythmic beating and resulted in a significant membrane injury as shown by release of LDH. The injury was prevented by catalase which removes H2O2 and by cell-permeable, metal-chelating agents such as desferrioxamine or bipyridine. In contrast, reagents which are excluded from the cell such as superoxide dismutase or DTPA did not protect the cells against H2O2. Five- and six-membered ring, stable nitroxide radicals which have previously been shown to chemically act as low-molecular weight, membrane-permeable, SOD-mimetic compounds provided full protection. The nitroxides prevented leakage of LDH and preserved normal cardiomyocyte contractility, presumably by intercepting intracellular O2-radicals. Alternatively, protection may result through nitroxides reacting with reduced transition metal ions or by detoxifying secondary organic radicals.

Animals↗
PubMed1991

Nitroxide SOD-mimics: modes of action.

Low molecular weight superoxide dismutase mimics have been shown to afford protection from oxidative damage. Such SOD-mimics can readily permeate cell membrane achieving sufficiently high levels both inside and outside the cell to effectively detoxify intracellular O2-.. Preliminary findings also indicated that metal-based and metal-free SOD-mimics can protect hypoxic cells from H2O2-induced damage. The present study explored the possibility that SOD-mimics such as desferrioxamine-Mn(III) chelate [DF-Mn] or cyclic nitroxide stable free radicals could protect from O2-.-independent damage. Killing of monolayered V79 Chinese hamster cells was induced by H2O2 or by t-butyl hydroperoxide (t-BHP) and assayed clonogenically. Neither catalase nor native SOD protected the cells from t-BHP. In contrast, both DF-Mn and cyclic nitroxides protected suggesting cytotoxic processes independent of O2-. or of O2-.-derived active species. The inhibition of the damage by both metal-free and metal-based SOD mimics is attributable to either SOD-mimic reacting with reduced transition metal to block the Fenton reaction and/or intercepting and detoxifying intracellular organic free radicals.

Animals↗
PubMed1991

In vitro photodynamic treatment of normal and human papilloma virus-transfected keratinocytes with photofrin II and red light.

Photodynamic therapy involves the use of light of appropriate wavelength to excite a photosensitizer to result in tissue destruction. The photosensitizer dihematoporphyrin ether and red light were used to treat normal and human papilloma virus type 18-transfected keratinocytes in vitro. Although both cell lines were sensitive to treatment, normal keratinocytes retained more dihematoporphyrin ether and were more sensitive to photodynamic therapy than were transfected cells. In vitro data fail to show the selective retention of dihematoporphyrin ether reported elsewhere in the literature in papillomas and tumors. We did not find selective uptake or retention of dihematoporphyrin ether by human papilloma virus-transfected cells, despite previously published in vivo data to the contrary. Dihematoporphyrin ether retention and thus selective photosensitivity of papillomas in vivo is not caused by individual cellular differences in the processing of dihematoporphyrin ether. In addition, because in vitro results may not parallel in vivo results, both in vivo and in vitro models must be investigated in the study of phototherapeutic agents.

Antiviral Agents↗
PubMed1991

The influence of volume on gastric emptying and fluid balance during prolonged exercise.

The purpose of this study was to determine the effect of ingesting approximately 800, 1200, or 1600 ml.h-1 of a carbohydrate (CHO) solution on gastric emptying (GE), ratings of stomach fullness (RF), plasma volume changes (PVC), electrolytes, fluid loss, and blood glucose (BG) during 2 h of cycling at 70% of VO2max. Eight male cyclists completed three rides during which they ingested either 11.5 (LV), 17.1 (MV), or 23 ml.kg-1.h-1 (HV) of a 7.5% CHO solution every 15 min. Blood samples were taken at 0, 60, 90, and 120 min and 15 min after the ride for the determination of PVC, sodium (Na+), potassium (K+), and BG. Body weight was recorded before and after the rides to determine dehydration. Rates of GE were determined via stomach aspiration after the rides. A significantly (P less than 0.05) greater volume of fluid was emptied in the HV trial (2268 +/- 70.8 ml) compared with the MV and LV trials (1860 +/- 72 and 1452 +/- 24 ml, respectively). The rate of GE in the MV trial was also significantly greater than in the LV trial. RF were significantly higher in the MV and HV trials compared with the LV trial throughout the rides. There were no significant differences in PVC (0.01 +/- 2.2%, 1.05 +/- 1.62%, and 0.97 +/- 1.28% for LV, MV, and HV, respectively), Na+, K+, or BG between the three trials. There was a significantly greater decrease in body weight in the LV (-0.77 +/- 0.14 kg) compared with the MV and HV trials (-0.38 +/- 0.13 and -0.14 +/- 0.14 kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Beverages↗
PubMed1991

Sensitization of low-dose-rate irradiation by nonlethal hyperthermia.

To assess whether hyperthermia could radiosensitize cells irradiated at a low dose rate, Chinese hamster V79 cells were simultaneously heated and irradiated at 0.86 Gy/h. The data showed that heat treatments at 39 and 40 degrees C, which did not induce heat killing alone or high-dose-rate radiosensitization, resulted in enhanced cell killing with low-dose-rate irradiation. The dose-modification factor (ratio of the slopes of the curves for low dose rate and high dose rate) was reduced to 1.8 at 39 degrees C and 1.4 at 40 degrees C, compared to a value of 2.1 at 37 degrees C. These data indicate that nonlethal heat treatments can cause enhanced radiosensitization under low-dose-rate conditions. The implications of these results for interstitial thermoradiotherapy are discussed.

Animals↗
PubMed1990

The role of serotonin in the development and environmental regulation of type II corticosteroid receptor binding in rat hippocampus.

Hippocampal concentrations of serotonin (5-HT) increase over the first two weeks of life, and show a peak on day 14. This pattern is very similar to the previously reported developmental changes in hippocampal type II corticosteroid receptor binding. We found that adult animals treated during the first days of life with the 5-HT neurotoxin, 5.7-dihydroxytryptamine, showed reduced hippocampal type II corticosteroid receptor binding. In addition, manipulations that resulted in increased hippocampal type II corticosteroid receptor binding, such as neonatal handling or exogenous thyroid hormone treatment also increased hippocampal 5-HT turnover. Finally, concurrent administration of the 5-HT2 receptor antagonist, ketanserin, blocked the effects of handling on hippocampal type II corticosteroid receptor binding. Taken together with the results of recent in vitro experiments, these data suggest that (a) 5-HT may be involved in the ontogenetic variation in hippocampal type II corticosteroid receptor binding, and (b) that increases in 5-HT activity may mediate the effects of environmental stimulation on hippocampal type II corticosteroid receptor binding.

5,7-Dihydroxytryptamine↗
PubMed1990

Sensitivity of different human lung cancer histologies to photodynamic therapy.

The relative sensitivities of different cancer histologies in a single site to photodynamic therapy (PDT) are unknown and methods to predict PDT sensitivity have not been described. The in vitro response to PDT of six established human lung cancer cell lines and one normal lung fibroblast cell line was studied using the clonogenic assay. Dose-response curves were determined for cells incubated in 25 micrograms/ml of Photofrin II for 2 h, followed by exposure to 630-nm light to total energies of 0-3150 J/m2. None of the cell lines were sensitive to sensitizer alone or light alone. Differences in inherent PDT sensitivities as evaluated by survival curve parameters n, Do, and light dose to yield 1% survival were observed among the cell lines. No clear correlation was found when inherent PDT sensitivity was compared with sensitizer uptake; however, a general association was noted between PDT sensitivity and the plating efficiency of the cell line. These data illustrate that differences in inherent PDT exist for in vitro systems. Such differences may explain some of the failures seen in clinical PDT.

Cell Line↗
PubMed1990

Biologically active metal-independent superoxide dismutase mimics.

Superoxide dismutase (SOD) is an enzyme that detoxifies superoxide (O2.-), a potentially toxic oxygen-derived species. Attempts to increase intracellular concentrations of SOD by direct application are complicated because SOD, being a relatively large molecule, does not readily cross cell membranes. We have identified a set of stable nitroxides that possess SOD-like activity, have the advantage of being low molecular weight, membrane permeable, and metal independent, and at pH 7.0 have reaction rate constants with O2.- ranging from 1.1 x 10(3) to 1.3 x 10(6) M-1 s-1. These SOD mimics protect mammalian cells from damage induced by hypoxanthine/xanthine oxidase and H2O2, although they exhibit no catalase-like activity. In addition, the nitroxide SOD mimics rapidly oxidize DNA-FeII and thus may interrupt the Fenton reaction and prevent formation of deleterious OH radicals and/or higher oxidation states of metal ions. Whether by SOD-like activity and/or interception of an electron from redox-active metal ions they protect cells from oxidative stress and may have use in basic and applied biological studies.

Animals↗