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Biomedical subjects

C Harris

Publications and source records attributed to C Harris.

At least 145 records · Page 8Linked to original sources
PubMed1993

Glutathione oxidation and embryotoxicity elicited by diamide in the developing rat conceptus in vitro.

This study was performed in the rat whole-embryo culture system to investigate the effects of glutathione oxidation by diamide, a thiol oxidant, in developing rat conceptuses during early organogenesis. The effects of diamide on reduced glutathione (GSH), glutathione disulfide (GSSG), and embryotoxicity were found to be concentration and time dependent. Diamide at concentrations of 75 and 100 microM produced abnormal axial rotation (62-89%), decreased viability (to 69% by 100 microM diamide), and reduced protein and DNA content in the embryo and visceral yolk sac (VYS) when evaluated on Day 11. High concentrations of diamide (250-500 microM) resulted in 100% mortality. GSH and GSSG levels in the conceptuses were not significantly affected during 2 hr following diamide addition at concentrations of 50 to 100 microM. At concentrations of 250 and 500 microM, rapid GSH depletion (50% of control) was seen within 5 min of exposure and was followed at 5-30 min by a significant increase in GSSG relative to control values. Diamide (500 microM) exposure for only 15 min on Gestational Day 10 was sufficient to elicit malformations (53% of exposed conceptuses with abnormal axial rotation) without significant loss of viability. After 30 min of exposure to the high concentration (500 microM), viability was decreased to 71% and defects of axial rotation increased to 87% in surviving conceptuses. This indicates that events associated with initial exposure are critical for expression of toxicity. Inhibition of glutathione disulfide reductase (GSSG reductase) activities in embryo and VYS with 1,3-bis(2-chloroethyl)-1-nitro-sourea prior to diamide addition potentiated the embryotoxicity of diamide (75 microM) and resulted in corresponding reductions in GSH/GSSG ratios as determined during the first 2 hr of exposure. Inhibition of new GSH synthesis with L-buthionine-[S,R]-sulfoximine during diamide (75 microM) exposure also exacerbated toxicity compared to diamide treatment alone. These results implicate the involvement of GSH synthesis and GSSG reductase activity in mediating the embryotoxicity of diamide.

Animals↗
PubMed1993

Glutathione biosynthesis in the postimplantation rat conceptus in vitro.

Glutathione (GSH) biosynthesis in Day 10 rat conceptuses was characterized in whole embryo culture by evaluation of net rates of GSH replenishment in whole conceptuses, embryos, and visceral yolk sacs (VYS); uptake and distribution of [35S]cysteine and [35S]methionine from the culture medium; incorporation of 35S-labeled amino acids into GSH; and efflux of [35S]GSH into the culture medium. Diethyl maleate (DEM, 500 microM) depleted intracellular GSH pools in embryo and VYS to 30% of control values within 45 min. Restoration of GSH pools in VYS began immediately and continued at a rate of 295 pmol/conceptus/hr until GSH concentrations exceeded initial control levels at 4 hr. GSH pools in the embryo remained depleted for over 2 hr, followed by resynthesis at initial rates of 118 pmol/conceptus/hr. [35S]Cysteine (0.2 mM) uptake from the culture medium resulted in whole conceptus accumulations that reached 1.6 nmol/conceptus. The portion of intracellular free cysteine obtained through uptake of extraconceptal amino acid was 40-90 pmol/conceptus and represented less than 20% of the total free intracellular cysteine. [35S]Methionine (0.2 mM) accumulation surpassed that of cysteine at all time points by two- to threefold. [35S]Cysteine, added 2 hr after DEM, was incorporated into GSH at rates of 126 pmol/conceptus/hr during the first hour. By 4 hr, rates of incorporation had declined to 22 pmol/conceptus/hr. L-Buthionine-[S,R]-sulfoximine (1 mM) completely eliminated incorporation of [35S]cysteine into GSH. Net efflux of [35S]GSH into the culture medium accounted for less than 40 pmol of total GSH when measured 5 hr after DEM addition. Although effectively transported into the conceptus and readily utilized in protein synthesis, 35S from methionine was not incorporated into GSH under any conditions tested. After chemical depletion, de novo GSH synthesis occurs exclusively in the VYS. Embryonic recovery begins only after GSH pools in the VYS are replete. Prolonged embryonic GSH depletion and slower recovery rates indicate that the embryo may be selectively susceptible to chemical insult following depletion of GSH.

Animals↗
PubMed1993

Case report of factor VII deficiency.

The case of a 57-year-old woman with no personal or family history of coagulopathy or blood dyscrasia who was found to be factor VII deficient by routine laboratory testing is reported. The patient was also found to have type 2 diabetes mellitus and adenocarcinoma of the uterus in the course of her hospitalization.

Adenocarcinoma↗
PubMed1993

Direct in vivo gene transfer to airway epithelium employing adenovirus-polylysine-DNA complexes.

Adenovirus-polylysine-DNA complexes were evaluated for their capacity to accomplish direct in vivo gene transfer to airway epithelium employing a rodent model. Binary complexes containing transferrin or adenovirus, or combination complexes containing both transferrin and adenovirus, were evaluated. The highest in vitro gene transfer efficiency in primary cultures of airway epithelial cells was accomplished by the combination complexes. This result was paralleled in vivo. Transient gene expression of up to 1 week was observed with localization of the transduced cells to the region of the small airways. These results establish the feasibility of this type of approach for gene therapy applications.

Adenoviridae↗
PubMed1993

Water of life.

Explore the source record for details and available documents.

Africa↗
PubMed1993

Osteoarthritis: how to diagnose and treat the painful joint.

Osteoarthritis (OA) is the most common form of arthritis in older patients, causing pain that can significantly reduce function and quality of life. OA is classified as either primary or secondary disease, depending on the underlying etiology. Causes of secondary OA include trauma, other joint disease, and metabolic conditions. Diagnosis is based on patient history, physical examination, and radiographic findings. The mainstay of treatment is the use of nonsteroidal anti-inflammatory agents; NSAIDs that can be given once or twice daily increase patient compliance. Other therapeutic measures include exercise programs and--in patients with severe pain and limited function--surgical intervention.

Aged↗
PubMed1992

Growth kinetics and chemoprevention of aberrant crypts in the rat colon.

Single and multiple colonic crypts exhibiting dysplasia that are detectable in situ by staining of rat colon with methylene blue are called aberrant crypts (AC) and may serve as an intermediate marker for colon cancer. In a characterization study, we have established the kinetics of AC growth and development over a period of 20 d following injection of rats with the carcinogen azoxymethane (AOM). AC are not present at 5 d post-injection, but are a constant feature at 10 d and thereafter. Multiple AC, presumably clonal, begin to evolve at 10 d and are consistent by 20 d, forming incipient microadenomata. We have examined 20 candidate chemopreventive agents for inhibition of AC. All agents were given in AIN-76 diet, at two dose levels, with injections of AOM. AC were measured after 5 weeks of growth. Among the most active AC-inhibiting agents were BHA, DFMO, quercetin, diallyl sulfide, 18 beta-glycyrrhetinic acid, and ascorbyl palmitate. In a post-initiation study, the differentiating agent sodium butyrate was ineffective, but piroxicam was highly effective in modulating AC growth. Further, piroxicam inhibited AC development at all stages of growth from single to polycryptal clusters of AC. The AC assay shows marked sensitivity and specificity for screening agents for chemoprevention of colon cancer.

Animals↗
PubMed1992

Unusual patterns of Histoplasma capsulatum meningitis and progressive multifocal leukoencephalopathy in a patient with the acquired immunodeficiency virus.

Disseminated histoplasmosis (DH) and progressive multifocal leukoencephalopathy occur in acquired immunodeficiency syndrome (AIDS). At autopsy, DH patients with central nervous system involvement almost always show extensive involvement of the lungs and reticuloendothelial system in addition to the brain, and progressive multifocal leukoencephalopathy is manifest as multiple demyelinating lesions in several locations in the brain. We describe an AIDS patient with a long history of aggressively treated DH who died with DH in the brain only; fungus was not found elsewhere at autopsy. In addition, there was a papovavirus infection restricted to the cerebellum with predominant involvement of the internal granular cell layer; again, demyelinating lesions were not found elsewhere in the brain. Each of these patterns of brain involvement is rare. As the incidence of AIDS increases and patients are treated aggressively, the frequency of unusual neuropathologic patterns of opportunistic infections may be expected to increase.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Functional aphonia in young people.

The study reviewed the case histories of 14 young aphonics. A questionnaire was completed by the five speech therapists involved with these cases. The patients were all initially examined by E.N.T. specialists and then treated by speech therapy. All the patients were 'cured' by speech therapy, that is the voice returned to its premorbid state. This study looks at common characteristics of presentation, different approaches to management, and the patterns of voice return.

Adolescent↗
PubMed1992

The objective assessment of abnormal eye movements in infants and young children.

Recordings of eye movements from infants and young children can be of clinical value in patients with certain neuro-ophthalmological problems. This requires that the characteristics of normal eye movements in this same age-group are known. Using an electro-oculographic technique in a specially developed laboratory we have been able to assess the saccades, binocular and monocular smooth pursuit, binocular and monocular optokinetic nystagmus (OKN), and sustained vestibular rotation in infants and young children; these recordings were performed in one session lasting approximately 35 minutes. The recordings from four children with abnormal eye movements (delayed visual maturation, hemicerebral cyst, congenital ocular motor apraxia, and gaze-paretic nystagmus) are briefly reported and compared to normal eye movements of age-related children. The limitations of this procedure are discussed.

Adolescent↗
PubMed1992

Physician-hospital networking: avoiding a shotgun wedding.

The erosion of the traditional market is forcing hospitals and physicians to reevaluate their historical relationships. One method for addressing the potential conflicts created by current pressures is the formation of physician-hospital networks. These entities are formed and function on the basis of mutual interests and responsiveness to change.

Economic Competition↗
PubMed1991

Fetotoxic alterations in the normal ontogenies of rat microsomal and lysosomal enzymes.

The activity patterns during development for acid phosphatase (Ac-P), alkaline phosphatase (A1-P), beta-glucuronidase (beta G), and UDP-glucuronyltransferase (UDPGT) have been determined in various tissues of the rat for corn oil and distilled water controls as well as in animals prenatally exposed to four fetotoxic chemicals. Postnatal assays were performed on both sexes separately. In control animals, tissue-specific differences between male and female activity levels were found for UDPGT. In the liver of mature offspring, enzyme activity was greater in males than in females. Although no sex difference was observed in the intestine, the kidneys of females exhibited higher values than those of males. An original computer-assisted methodology is presented, designed (a) to permit a mathematical description for the complex curves exhibited by these ontogeny profiles, and (b) to assess the statistical significance of chemical-induced alterations in these complex developmental patterns, specifically, to target sensitive periods and subtle changes near the fetotoxic threshold. Oral administration (days 6-18 of gestation) of 3,3',4,4'-tetrachlorobiphenyl (4CB) to pregnant females resulted in an induction of liver UDPGT activity in offspring postnatally, and some alterations in the perinatal pattern of beta G in the same tissue. This treatment also produced differences in the intestinal patterns of Ac-P and male UDPGT. No significant changes were observed in offspring exposed to diethylstilbestrol (DES). Treatment with zeranol (ZN) caused reductions in activity over the entire postnatal period for beta G in liver, brain, intestine, and kidney, for A1-P in brain, and for Ac-P in the intestine. Cadmium-treated dams gave birth to offspring that exhibited slightly altered ontogenies only in intestine for UDPGT and AcP. The alterations in these developmental profiles indicate periods of increased sensitivity, and may be useful in directing more specific studies into the fetotoxic mechanisms of these compounds.

Acid Phosphatase↗
PubMed1991

Morphological differences elicited by two weak acids, retinoic and valproic, in rat embryos grown in vitro.

We compared in rat whole-embryo culture the morphological changes elicited by valproic acid (VPA) with those elicited by trans-retinoic acid (RA). Rat embryos explanted on day 9.5 of gestation were treated on day 10 with RA or VPA at concentrations producing equivalent reductions in embryonic protein. The concentrations selected for morphological assessment by scanning and transmission electron microscopy, 2.3 and 800 microM, respectively, for RA and VPA, produced approximately a 50% incidence of abnormally open anterior neuropores in initial range-finding experiments in the culture system. Protein and DNA analyses were also performed on corresponding groups of embryos at three different doses. With concurrent control groups used as reference standards, the two treatment groups were compared for differences in external and internal morphology, protein and DNA contents, and growth indices. While certain variables responded similarly in the two treatment groups, e.g., the growth variables, protein and DNA contents, each drug produced selective morphological effects. Whereas treatment with RA produced underdeveloped branchial arches, symmetrically cleft cranial defects resulting in openings in rhombencephalic and prosencephalic regions, and exteriorized neural tissue in the caudal neuropore region, VPA produced irregular clefts with wavy margins along the entire length of the neural tube, and an open caudal neuropore without eversion of the neuroepithelium, while producing no detectable effect on the branchial arches. The similar effects of these two drugs on protein and DNA contents suggest comparable degrees of overall toxicity; however, the dissimilar effects on neural tube and branchial arches, coupled with the large difference in concentration of the drug required to produce the effects, add to the evidence that their mechanisms for elicitation of abnormal development are qualitatively different.

Animals↗