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Biomedical subjects

R H Matthews

Publications and source records attributed to R H Matthews.

At least 19 recordsLinked to original sources
PubMed2000

Prophylactic cranial irradiation in small-cell lung cancer.

Prophylactic cranial irradiation is now known to improve survival to a significant degree in small-cell lung cancer (SCLC) patients; this is in addition to its established role in preventing the disabling symptoms of brain metastases. New information indicates that it confers a survival benefit for limited or extensive stage SCLC patients gaining a complete response in the chest. A review of causes of cerebral dysfunction as a complication indicates that such problems can be due to suboptimal radiation fractionation, chemotherapy, or an inappropriate combination of prophylactic brain irradiation with chemotherapy. Optimum treatment with prophylactic brain irradiation has been shown not to cause adverse effects with detailed psychometric testing. Several additional sources of information can be drawn together to suggest a dose-response pattern for prophylactic brain irradiation, leading to the recommendation that a dose of 25-36 Gy is optimal, delivered in 2-3 Gy daily fractions after the completion of chest irradiation and chemotherapy. This will be better defined in future clinical trials.

Brain Neoplasms↗
PubMed1996

Effects of 4-hydroxynonenal and N-acetyl-L-cysteine on Myc-induced apoptosis.

Apoptosis has been described as programmed active cell death. Overexpression of the c-Myc gene has been shown to induce apoptosis in Rat1A/Myc-ER cells when combined with a growth blocking agent. In the present study, we tested whether 4-Hydroxynonenal (HNE) or N-acetyl-L-cysteine (LNAC) affect apoptotic death in serum deprived Rat1A/Myc-ER cells caused by the c-Myc protein. The incidence of apoptosis in growth arrested cells was confirmed photographically and by ladder pattern formation seen on agarose gel electrophoresis. To study the effect of HNE and LNAC, the cells were cultured in 0.5% serum and treated with various concentrations of HNE and LNAC, c-Myc was then activated by addition of 2 microM beta-estradiol. Two separate parameters were used to determine the rate of cell death. In the first, the amount of DNA isolated from dying cells was compared by UV absorption. As the second parameter, the cell numbers were determined by counting. Our results showed that 1 microM of HNE has no effect on apoptotic cell death. However, 10 microM HNE decreased the amount of DNA isolated while increasing the cell count 14% relative to cells treated only with beta-estradiol. In addition, we found that various concentrations of the antioxidant LNAC does not protect cells from c-Myc induced death. However, it supports cell survival in 0.5% serum and causes an increase in cell number.

Acetylcysteine↗
PubMed1996

High-performance liquid chromatography assay for N-acetylcysteine in biological samples following derivatization with N-(1-pyrenyl)maleimide.

N-Acetylcysteine is a thiol antioxidant with expanding clinical importance. A sensitive, rapid method for determining reduced N-acetylcysteine (NAC) concentration in biological samples has been developed which uses a modified reversed-phase high-performance liquid chromatography (HPLC) technique in conjunction with the derivatizing agent N-(1-pyrenyl)maleimide (NPM). The NAC-NPM adduct was analyzed by HPLC with fluorescence detection. The calibration curve for NAC was linear over the range 8-2500 nM and the coefficient of variation obtained for the within-run precision and the between-run precision for 0.5 mM NAC was 1.5% and 2.7%, respectively. Relative recovery of NAC from biological materials ranged between 86% and 96% and the limit of quantitation from biological samples was 32 nM. These results suggest practical advantages relative to other widely-accepted methods of NAC measurement.

Acetylcysteine↗
PubMed1996

N-actylcysteine protects Chinese hamster ovary (CHO) cells from lead-induced oxidative stress.

In vitro administration of lead acetate (PbA) to cultures of Chinese hamster ovary (CHO) cells had a concentration-dependent inhibitory effect on colony formation. Colony formation was returned to control levels in lead-treated cultures that were supplemented with 1 mM N-actylcysteine (NAC), a well-documented synthetic antioxidant. In order to investigate the nature of NAC's protective effect, we measured L-gamma-glutamyl-L-cysteinylglycine (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA) and catalase activity both in the presence and absence of NAC in lead-exposed CHO cells. Increases in both MDA levels (p < 0.05) and catalase activity (P < 0.05) were observed in cultures that received only PbA, but supplementation with NAC returned these measures to pretreatment levels. The ratio of GSH to GSSG increased in lead-exposed cells incubated in NAC-enhanced media, but declined in cultures treated with PbA only. Our results suggest that NAC can confer protection against lead-induced oxidative stress to CHO cells, possibly through the enhancement of the cell's own antioxidant defense mechanisms.

Acetylcysteine↗
PubMed1996

In vitro study of the metabolic effects of D-amino acids.

While the L-configuration of amino acids predominates in all known living systems, D-enantiomers of amino acids have been detected with highly sensitive chromatographic techniques in human physiological fluids. In the present study, the survival of Chinese hamster ovary cells (CHO) and HeLa cells was inhibited by exposure to high concentrations of some D- or L-amino acids. Inhibition of colony formation, though, was not necessarily observed to be chiral-dependent. Some L-amino acids (LAAs) were found to be toxic while other D-amino acids (DAAs) were innocuous in both cultures. This is contradictory to the previous observations that DAAs were generally considered to be harmful. Frequently it was implied, although not experimentally proven, that the LAAs were not toxic. One of the metabolites produced by oxidative deamination of D- or LAAs is hydrogen peroxide (H2O2), a reactive oxygen species (ROS) that is decomposed by catalase. Increased intracellular H2O2 can result in peroxidation of lipids. We measured catalase activity and the lipid peroxide levels (LPO) after incubating cells in either D- or LAAs. The amino acids (AAs) that were found to inhibit colony formation were found to be associated with higher levels of catalase activity and LPO. Therefore, we hypothesize that enhanced ROS generation may be, in part, responsible for the observed toxicity of some amino acids.

Amino Acids↗
PubMed1996

In vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by treatment with meso-2,3-dimercaptosuccinic acid or N-acetylcysteine.

Knowledge of lead's capacity to disrupt the prooxidant/antioxidant balance within mammalian tissues suggests that definitive therapy for chronic lead poisoning should encompass both chelating and antioxidant actions. The dithiol meso-2,3-Dimercaptosuccinic Acid (DMSA) is the first orally administered metal chelating agent to receive U.S. Food and Drug Administration (FDA) approval for the treatment of childhood plumbism and possesses the potential to function as an antioxidant by removing lead from the site of deleterious oxidation reactions. Five weeks of lead exposure was found to deplete glutathione (GSH) levels, increase oxidized glutathione (GSSG), and promote malondialdehyde (MDA) production in both liver and brain samples taken from C57BL/6 mice. GSH levels increased and GSSG and MDA levels decreased in groups of lead-exposed mice that received 1 mmol/kg DMSA or 5.5 mmol/kg N-acetylcysteine (NAC) for 7 d prior to sacrifice. Treatment with DMSA caused a reduction in blood, liver, and brain lead levels consistent with its function as a chelating agent, while treatment with NAC did not reduce these lead levels. However, NAC did cause a reduction in indices of oxidative stress in both brain and liver samples, which implies that this synthetic thiol-containing antioxidant is capable of abrogating lead-induced oxidative stress in vivo. Overall, these results suggest that lead-induced oxidative stress in vivo can be mitigated by pharmacologic interventions, which encompass both chelating as well as thiol-mediated antioxidant functions.

Acetylcysteine↗
PubMed1996

Prevention of mucositis in irradiated head and neck cancer patients.

Mucositis has been a significant debilitating side effect to the treatment of head and neck cancer by irradiation. A change in prophylactic treatment policy was made in August 1991 such that a total of 59 patients was divided into two groups. In Group A, 37 patients were treated prophylactically principally by sucralfate; while in Group B, 22 patients were treated by a three-part prophylactic regimen consisting of sucralfate, either cipriofloxacin or ampicillin, and clotrimazole troches. In Group A patients, unless they had limited fields as for stage 1 vocal cord patients, they uniformly progressed from patchy to confluent or severe mucositis (31/37 severe mucositis). Of the 22 patients in Group B, three patients also arrived at completion of treatment with severe or confluent mucositis; 12 of 22 experienced mild to patchy mucositis by completion, and seven of 22 retained their mucosa entirely intact at the completion of treatment. Four of 22 patients in Group B encountered a clinically diagnosed herpes virus infection of the oropharynx during treatment, which improved when Zovirax was added to their regimen. We conclude that mucositis is clearly and markedly improved by utilization of our prophylactic regimen for Gram-negative rods and fungi.

Ampicillin↗
PubMed1995

Analysis of glutathione, glutathione disulfide, cysteine, homocysteine, and other biological thiols by high-performance liquid chromatography following derivatization by n-(1-pyrenyl)maleimide.

The compound N-(1-pyrenyl)maleimide (NPM) reacts with free sulfhydryl groups to form fluorescent derivatives. A new method for measurement of glutathione and other biological thiols utilizing reverse-phase high-performance liquid chromatography to separate and quantify these derivatives is described. Separation and quantification of glutathione, cysteine, homocysteine, cysteinylglycine, and gamma-glutamylcysteine derivatives are achieved. The method allows for the measurement of glutathione disulfide by masking free glutathione with 2-vinylpyridine, reducing glutathione disulfide with glutathione reductase, and measuring the resulting glutathione. Coefficient of variations for the various thiols measured by the NPM method range from 1.5 to 8.8%. The lower detection limit is around 50 fmol of glutathione. NPM derivatives are shown to be stable for 2 months at 4 degrees C. Between 94.2 and 97.2% of glutathione and/or glutathione disulfide added to a sample is recovered using the NPM method. The NPM method is compared to the monobromobimane high-performance liquid chromatography method and the Tietze assay by measuring glutathione in homogenates from five different cell lines. The newly developed method offers some advantages over the currently accepted techniques, including specificity, speed, sensitivity, and ease of use.

Animals↗
PubMed1995

Nutrient Databank perspectives on energy.

The Atwater system of food-specific factors continues to be used for calculating energy in the Nutrient Databank. In 1983 the US Department of Agriculture requested that the Life Sciences Research Office (LSRO) of the Federation of American Societies for Experimental Biology reassess the system's accuracy and utility. An LSRO panel of experts reported that there was no evidence that a substantial problem exists. Advances in food technology and changes in analytical methods in the past decade, however, are causing some concern for the reporting of energy in the databank. Some perspectives on these and other issues are discussed.

Databases, Factual↗
PubMed1992

Nodular poorly differentiated lymphocytic lymphoma of the thyroid.

A 44-year-old woman had a four-month history of enlargement of her thyroid. Evaluation revealed a rare disease: nodular, poorly differentiated lymphocytic lymphoma of the thyroid (NPDL), stage IE. A review of the literature revealed that most thyroid lymphomas are diffuse histiocytic (DH). Treatment of thyroid lymphocytic lymphoma and survival rates have been quite variable between institutions. There are no large studies to guide the physician in making a management plan to treat thyroid NPDL. Our patient was treated with a combination of chemotherapy and radiation therapy (XRT).

Adult↗
PubMed1988

Prognostic implications of age in breast cancer patients treated with tumorectomy and irradiation or with mastectomy.

Conservation breast treatment is of particular interest to young women, but whether saving the breast carries a penalty in shorter survival or local-regional recurrent disease has not been well-established. At The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston, 1161 patients treated prior to 1983 with Stage I or II breast cancer were reviewed. Of these patients, 378 were treated with tumorectomy plus irradiation, and 783 were treated with radical or modified radical mastectomy. The two patient groups were compared relative to local-regional disease recurrence and overall and disease-free survivals. Local recurrences in the breast appear to be more frequent in patients less than or equal to 35 years of age treated with tumorectomy and irradiation than in patients older than 35 years, but in patients aged less than or equal to 50 or greater than 50 or less than or equal to 35 or greater than 35 years, there was no significant statistical difference between tumorectomy and irradiation or mastectomy nor was there a difference in disease-free survival. Overall survival rates favored patients treated by tumorectomy and irradiation.

Adult↗
PubMed1987

Lymphocyte function and abdominal operations. Trauma vs elective surgery.

An alteration of in vitro phytochemagglutinin-induced lymphocyte transformation immediately following abdominal trauma has been demonstrated. In this study the results of lymphocyte transformation in 30 patients who had suffered abdominal trauma (27 laparotomies; three observed) were compared with those of 20 patients who had undergone laparotomy for elective surgical problems. Response to mitogen was measured by incorporation of tritiated thymidine as a function of lymphocyte concentration, with a constant amount of phytochemagglutinin and a standard incubation period. A saturation curve was obtained, and lymphocyte response was measured as the concentration necessary for half-maximal incorporation of the radioactive label. No alteration of in vitro lymphocyte response was present in patients after elective abdominal or abdominal wall operations. In contrast, lymphocyte transformation was markedly depressed in patients who underwent surgery following abdominal trauma.

Abdominal Injuries↗
PubMed1984

Assessment of mammary lactogenic receptor changes in pregnant rabbits.

Lactogenic receptor was purified from rabbit mammary tissue and used to generate an antiserum in goats. The purified lactogenic receptor material bound lactogenic hormones specifically and reversibly. Antiserum generated in a goat bound a labeled human growth hormone/receptor complex; this was displaced by nonlabeled solubilized receptor preparations. This was used as a radioimmunoassay and was able to detect 0.037 fmol of lactogenic receptor. The specificity of the radioimmunoassay for lactogenic receptor was supported by three lines of evidence; first, the ligand used in the radioimmunoassay was an iodine 125-labeled human growth hormone/receptor combination; therefore, only membrane protein with structural homology to the protein which bound 125I-labeled human growth hormone competed for binding to the antiserum; second, depletion of radioreceptor binding sites by affinity chromatography with ovine prolactin as the fixed ligand was detected; third, an increase in breast lactogenic receptor during pregnancy was detected by both radioreceptor assay and the radioimmunoassay. We found a progressive increase in lactogenic receptors by radioimmunoassay which corresponded to parallel increases by radioreceptor assay in rabbit mammary tissue during pregnancy.

Animals↗
PubMed1984

Nutritive value of selected variety breads and pastas.

Nine types of commercially produced variety breads, plain bagels, corn tortillas, and three types of pasta products were obtained from each of four cities, New York, San Francisco, Atlanta, and Kansas City. Proximate components and 12 minerals and vitamins were determined in these and in cooked pasta products. Available carbohydrate and energy values were calculated. On the average, French, Italian, and pita breads were lower in moisture than other breads. Protein in bread products averaged between 7.6% and 10.4% and in cooked pastas and tortillas between 4.4% and 5.3%. Bagels averaged 10.2% protein. Insoluble dietary fiber in whole wheat bread averaged 5.6%; for most products, dietary fiber values were five- to eightfold higher than crude fiber values. Pasta products and tortillas were virtually free of sodium. Sodium in bread products averaged between 379 and 689 mg/100 gm. Although all pasta products and most bread products were enriched, calcium was often not included. Iron averaged from 2.16 to 3.29 mg/100 gm in bread products and 3.10 to 4.24 mg/100 gm in dry pasta products. Products made with unrefined or less-refined flours and/or containing germ and bran tended to be high in phosphorus, magnesium, zinc, and manganese, and, to a lesser extent, in copper. A good portion of potassium, thiamin, riboflavin, and niacin in pasta products was lost during cooking.

Bread↗
PubMed1982

Hormone dependence of 7,12-dimethylbenz[a]anthracene-induced mammary tumor growth: correlation with prostaglandin E2 content.

Prostaglandin content in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors was correlated with growth responses to alterations in endogenous estrogen and prolactin. Prostaglandin E2 (PGE2) content varied inversely with tumor latency. Ovariectomy of tumor-bearing Sprague-Dawley rats resulted in regression of tumors in 90% of the castrated rats. PGE2 content in tumors from ovariectomized rats was elevated twofold (P less than 0.05) compared to PGE2 content in tumors from intact controls. Haloperidol treatment promoted tumor growth even after ovariectomy and returned tumor PGE2 values to control levels. Tumors grouped by growth status irrespective of hormone status showed an inverse relationship between PGE2 content and growth response.

9,10-Dimethyl-1,2-benzanthracene↗