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Biomedical subjects

A C Miller

Publications and source records attributed to A C Miller.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of glutathione reductase activity by a carbamoylating nitrosourea: effect on cellular radiosensitivity.

Nitrosoureas inactivate cellular glutathione reductase. N,'N'1,3-bis(trans-4-hydroxycyclohexyl)-N'-nitrosoureas (BCyNU), a nitrosourea reported to selectively inhibit glutathione reductase (GR) activity, was examined to determine if it could be used as a means to inhibit cellular levels of this enzyme in radiobiology studies. Confirmation of drug-induced inhibition of GR activity was demonstrated using a cell-free model system employing purified GR. Cellular studies with Chinese hamster V79A03 showed that BCyNU decreased cellular glutathione content concomitant with an inhibition of specific GR activity. Under relatively nontoxic conditions, cellular exposure to BCyNU (25 microM, 0.25 h) either before or after radiation treatment, increased cellular radiosensitivity with the optimum time for drug addition being immediately following radiation. At a BCyNU dosage which produced less than or equal to 5% cell toxicity, a marked decrease in radioresistance was characterized as a reduction in both Dq (24 +/- 1.5%) and Do (8 +/- 0.5%) concomitant with a 25 +/- 2% decrease in cellular glutathione reductase (GR) activity. At cytotoxic drug dosages (25 microM, 1 h; cell survival 79 +/- 7%), a marked radiosensitization manifested by a 1.25 +/- .07-fold reduction in the Dq was observed concomitant with a 49 +/- 4% decrease in GR activity. Using cells enriched in different stages of the cell cycle, BCyNU caused cell-age dependent cytotoxicity with preferential killing of cells in the radioresistant late-S-phase, a likely explanation for its radiosensitizing capabilities at high drug dosages. Data obtained at nontoxic drug dosages suggest that GR-inactivation may be an important component of cellular response to free-radical induced damage.

Animals↗
PubMed1992

Stress, appraisal, and coping in mothers of disabled and nondisabled children.

The cognitive-behavioral model of stress and coping provided the framework for this study of mothers of physically disabled children (n = 69) and mothers of nondisabled children (n = 63). The first aim was to test for differences between groups in responses to stressful parenting events. As hypothesized, mothers of disabled children reported higher levels of depressive symptomatology. Differences in psychological distress and health status approached significance. The second aim was to explore the mediating influences of coping strategies and cognitive appraisals. As predicted, emotion-focused coping was related to increased psychological distress in mothers of disabled children whereas problem-focused coping was associated with decreased distress. Both relationships were significant even after controlling for differences in type of parenting stressor. Hierarchical regressions showed that 58 and 25% of the variance in psychological distress was explained by the independent variables; however, the predictors were different for the two groups of mothers. Factors that may explain the differential effectiveness of coping and appraisal, and clinical implications of this study are discussed.

Adaptation, Psychological↗
PubMed1991

Brain protein synthesis in rabbits following low level aluminium exposure.

1. Infant rabbits received s.c.injections 3 times weekly of low doses of aluminium (A1) maltolate (0.5-1.5 mg Al/kg body wt) or aluminium lactate (8 mg Al/kg body wt) from 5 or 10 days of age to 14 or 22 days of age. 2. Brain was used to provide a cell-free protein synthesizing system and this system exhibited increased activity in preparations from Al-exposed infants. The mRNA fraction obtained from the brain polysomal RNA also was more active following Al exposure. 3. The synthesis of immunoprecipitable calmodulin was significantly elevated.

Aluminum↗
PubMed1991

DNA damage in cultured human skin fibroblasts exposed to excimer laser radiation.

Ultraviolet excimer lasers are being considered for use in a variety of refractive and therapeutic procedures, the long-term biologic consequences of which are unknown. The effect of sublethal doses of 193-nm laser radiation on cellular DNA was examined in cultured human skin fibroblasts. In contrast to 248 nm, treatments with the 193-nm laser radiation below 70 J/m2 did not cause significant pyrimidine dimer formation in the skin cells. This was indicated by the lack of excision repair activities (unscheduled DNA synthesis assay), and further demonstrated by direct analysis of pyrimidine dimers in DNA from irradiated cells. However, a low level of unscheduled DNA synthesis could be detected following irradiation at 193 nm with 70 J/m2. Both the 193-nm and 248-nm radiation were able to induce chromosomal aberrations, as indicated by a micronucleus assay. A dose-dependent increase in micronuclei frequency was observed 48 and 72 h after laser irradiation. These results indicate that exposure of actively replicating human skin fibroblasts to sublethal doses of either 193- or 248-nm laser radiation can result in genotoxicity.

Cell Survival↗
PubMed1991

The laryngeal mask airway. An unusual complication.

The laryngeal mask airway is an important addition to the anaesthetist's armamentarium, but its use is not without the possibility for misfortune. We encountered an unusual and potentially serious complication. A patient's epiglottis became trapped between the pliable grates in the mask portion of the laryngeal mask and partially obstructed his airway. Should this problem occur and remain unnoticed, in addition to the problem of airway obstruction during the anaesthetic, the oedematous epiglottis could be severely injured upon removal of the laryngeal mask. This, in turn, could result in airway obstruction requiring emergency treatment.

Adult↗
PubMed1991

Hookworm folliculitis.

A case of persistent folliculitis in a 21-year-old man was demonstrated to be due to Ancylostoma caninum larvae. Treatment with oral thiabendazole was curative. Cutaneous larva migrans may be due to A caninum, but this presentation appears to be unique. The literature concerning etiology and pathogenesis of larva migrans is discussed with reference to this case.

Adult↗
PubMed1991

Increased radiation resistance in transformed and nontransformed cells with elevated ras proto-oncogene expression.

The cellular Ha-ras oncogene, activated by missense mutations, has been implicated in intrinsic resistance to ionizing radiation. This study shows that the overexpression of the unmutated gene (proto-oncogene) may also be involved in how the cells respond to radiation. The experimental system consisted of mouse NIH 3T3-derived cell lines which carry multiple copies of a transcriptionally activated human c-Ha-ras proto-oncogene. Both tumorigenic (RS485) and revertant nontumorigenic subclones (PR4 and 4C3) which have high levels of ras expression exhibited a marked increase in radioresistance as measured by D0 compared to control NIH 3T3 cells. Other nontransformed cells with elevated levels of ras (phenotypically revertant line 4C8-A10) also had a significantly increased resistance to radiation, further indicating an association between ras and radioresistance. The increased radioresistance of the RS485 and phenotypic revertants could not be explained by a differential expression of the myc or metallothionein I genes or by variations in cell cycle. The correlation between increased ras proto-oncogene expression and radioresistance suggests that the ras encoded p21, a plasma membrane protein, may participate in the cellular responses to ionizing radiation.

Animals↗
PubMed1990

The turtle's revenge: a case of soft tissue Mycobacterium chelonae infection.

A case of cutaneous Mycobacterium chelonae infection with sporotrichoid spread and extensive antibiotic resistance is presented. Control of this problem was only achieved after extensive debridement and grafting of the involved limb. The importance of surgery in management is discussed and the literature is reviewed.

Aged↗
PubMed1990

Translatability of mRNA from brain of infant rabbits exposed chronically to aluminium.

1. Polysomes were isolated from the brain of infant rabbits at 22 days of age. The animals received s.c. injections 3 times weekly of aluminium (Al) maltolate (3 mg Al/kg body wt) or Al lactate (16 mg Al/kg body wt) from 5 days of age. 2. The polysomes were used to direct the incorporation of [14C]leucine into peptides in a brain protein synthesizing system and exhibited a decreased activity when obtained from aluminum exposed infants. 3. The mRNA obtained from the polysomes was used to direct the incorporation of [35S]methionine into peptides in an mRNA dependent rabbit reticulocyte lysate. The translatability of the mRNA derived from aluminum exposed infant brains was significantly lower than that of preparations from control infant rabbits. 4. Al bound to maltolate, a ligand soluble in lipids as well as water, was considerably more detrimental to brain protein synthesis than Al bound to lactate.

Aluminum↗
PubMed1989

A prospective trial of prophylactic intravenous immune globulin for the prevention of infections in severely burned patients.

A prospective randomized double-blind study evaluated the efficacy of i.v. immune globulin in preventing infectious complications in severely burned patients. Fifty patients were randomized to receive either i.v. immune globulin or placebo. Each group of patients was treated with twice weekly infusions for either 5 weeks or until the patients' wounds were covered. Patients treated with the immune globulin had an immediate correction of their depressed serum IgG levels, however there was no change in the infection or mortality rates. No adverse effects were noted with the immune globulin treatments. One potential weakness of this study was the greater burn surface area and a higher incidence of inhalation injury in adult patients treated with i.v. immune globulin compared to controls.

Adolescent↗
PubMed1987

Clinical observations concerning active duty veterans with post-Vietnam adjustment problems.

Clinical observations by Navy psychiatrists and psychologists who concurrently conducted therapy groups at three separate military treatment facilities between 1981 and 1984 were recorded. The reasons they returned to active duty or remained in the service, how and why they were referred to therapy, issues that arose in group therapy, and factors that were believed to have influenced the successful outcome are summarized and discussed.

Adult↗
PubMed1986

Eosinophilic infiltration with flame figures. A distinctive tissue reaction seen in Wells' syndrome and other diseases.

We report five cases, all male, of diverse clinical findings of scattered erythematous, violaceous, or centrally blue plaques. Eight biopsies from the five patients showed nodular or diffuse dermal and subcutaneous infiltration, predominantly of eosinophils and histiocytes, with "flame figures" composed of granules of eosinophils that surround collagen bundles, whose staining quality is thereby altered. Two patients were children, the younger only 18 months old. Three patients initially presented clinical evidence of insect bites, and in one of these the biopsy showed cutaneous pseudolymphoma underlying dermal changes of eosinophilic cellulitis. Eosinophilic infiltration with flame figures is a distinctive reaction to various stimuli. It may be seen in a wide variety of clinical conditions and is not confined solely to patients with Wells' syndrome, which may be an acceptable term for clinically typical cases. Eosinophilic infiltration with flame figures is preferred descriptively to identify the microscopic changes in Wells' syndrome and in other cases like that of our patient with pseudolymphoma, in which the cutaneous reaction may be secondary to some other disease.

Adult↗
PubMed1986

The influence of cellular glutathione content on cell survival following photodynamic treatment in vitro.

The influence of cellular glutathione (GSH) levels on the response to photodynamic treatment (PDT) in vitro was determined in cells which either were depleted of GSH by buthionine sulfoximine (BSO) or were genetically GSH deficient. The effects of GSH depletion on cellular radiosensitivity were studied in parallel for the purpose of comparison. BSO treatments which reduced GSH levels in four cell lines (CHO, V79, EMT6, RIF) to approximately 80% of controls, 30% of controls, or undetectable levels uniformly decreased cell survival. This decrease was directly related to GSH depletion levels and was expressed mainly in a reduction of the width of the survival curve shoulder (Dq). GSH level-dependent aerobic radiosensitization following BSO treatment was likewise found in all four cell lines. In contrast to PDT, however, cell survival changes were expressed in the dose slopes (Do's) of the survival curves. Cell survival of GSH-deficient human fibroblasts (GM 3877) was decreased following PDT and gamma irradiation when compared to their normal counterparts (GM 5659). In both modalities the difference was mainly due to a reduction in the Dq's, while the Do's were only slightly affected. The augmented response to PDT was not caused by interference by BSO or GSH with either cellular porphyrin uptake or singlet oxygen production during the photodynamic process. Possible mechanisms of GSH effects on PDT were discussed.

Animals↗
PubMed1986

Effects of scavengers of reactive oxygen and radical species on cell survival following photodynamic treatment in vitro: comparison to ionizing radiation.

The effects of various scavengers of reactive oxygen and/or radical species on cell survival in vitro of EMT6 and CHO cells following photodynamic therapy (PDT) or gamma irradiation were compared. None of the agents used exhibited major direct cytotoxicity. Likewise, none interfered with cellular porphyrin uptake, and none except tryptophan altered singlet oxygen production during porphyrin illumination. The radioprotector cysteamine (MEA) was equally effective in reducing cell damage in both modalities. In part, this protection seems to have been induced by oxygen consumption in the system due to MEA autoxidation under formation of H2O2. The addition of catalase, which prevents H2O2 buildup, reduced the effect of MEA to the same extent in both treatments. Whether the remaining protection was due to MEA's radical-reducing action or some remaining oxygen limitation is unclear. The protective action of MEA was not mediated by a doubling of cellular glutathione levels, since addition of buthionine sulfoximine, which prevented glutathione increase, did not diminish the observed MEA protection. The hydroxyl radical scavenger mannitol also afforded protection in both kinds of treatment, but it was approximately twice as effective in gamma irradiation as in PDT. This is consistent with the predominant role of OH radicals in ionizing radiation damage and their presumed minor involvement in PDT damage. Superoxide dismutase, a scavenger of O2, acted as a radiation protector but was not significantly effective in PDT. Catalase, which scavenges H2O2, was ineffective in both modalities. Tryptophan, an efficient singlet oxygen scavenger, reduced cell death through PDT by several orders of magnitude while being totally ineffective in gamma irradiation. These data reaffirm the predominant role of 1O2 in the photodynamic cell killing but also indicate some involvement of free radical species.

Animals↗
PubMed1986

Effect of DL-buthionine-S,R-sulfoximine on the growth of EMT6 and RIF mouse tumors.

The response of murine EMT6 and RIF tumors to DL-buthionine-S, R-sulfoximine (BSO), a glutathione (GSH) depletor, given either as a single dose, continuous oral administration, or in multiple doses, was determined with the use of a tumor-growth-delay assay. BSO consistently caused significant tumor growth delay in EMT6 tumors, which reached 5-7 days (two doubling times) after a single BSO dose (40 mumol/kg or 4 mmol/kg), 3 days (one doubling time) with continuous oral administration (20 mM), and 9 days (three doubling times) with daily BSO administrations (4 mmol/kg) starting at the time of tumor inoculation. Growth inhibition persisted after discontinuation of BSO treatment. Some complete tumor regressions were observed. Only slight tumor growth delay (one doubling time) was observed in RIF tumors at all treatment modes. No direct correlation was observed between tumor GSH content and the effects on tumor growth. In vitro BSO pretreatment (2 mM, 24 hr) of EMT6 tumor cells prior to tumor inoculation, which reduced cellular GSH levels to 34% of controls, did not influence subsequent tumor growth. Pretreatment of mice with BSO (4 mmol/kg, 1 daily sc injection for 7 days) prior to tumor inoculation led to a reduction of tumor takes by 25% when compared to 100% tumor takes in untreated mice. These data imply a BSO-induced change in the host response to tumor development.

Animals↗
PubMed1985

Neurotropic malignant melanoma: a novel treatment approach combining modified microscopically controlled surgery and S100 immunohistochemical staining.

Treatment of neurotropic malignant melanoma of the nasal ala combining microscopically controlled surgery and examination of formalin-fixed paraffin-embedded tissue cut in the horizontal plane followed by S100 immunohistochemical staining is described. The spindle-shaped cells were strongly S100 positive and detection of the melanoma cells, which were embedded in a dense collagenous stroma and infiltrating into the neurovascular spaces, was greatly accentuated by the S100 immunohistochemical stain. The coordinated skills of the dermatologic surgeon, dermatopathologist, and plastic surgeon contributed toward the best treatment for neurotropic melanoma in this patient.

Combined Modality Therapy↗