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Biomedical subjects

J Alexander

Publications and source records attributed to J Alexander.

At least 487 records · Page 27Linked to original sources

Use of ethopropazine and BW 284C51 as selective inhibitors for cholinesterases from various species.

Both inhibitors tested were still able to depress the cholinesterase (ChE) for which it is not selective (BW 284C51 for pseudo ChE, ethopropazine for the true ChE) provided the concentration was high (greater than 10(-2) M). BW 284C51 totally depressed the true ChE activity from bovine erythrocytes at a concentration of 10(-6) M. This inhibitor concentration gave no depression of pseudo ChE activity from horse serum. Ethopropazine totally depressed the pseudo ChE activity from horse serum at a concentration of 5 X 10(-5) M. The true ChE was not inhibited at this concentration. For true ChE from bovine erythrocytes and pseudo ChE from horse serum BW 284C51 and ethopropazine therefore certainly have a potential as selective ChE inhibitors. Ethopropazine at a concentration of 5 X 10(-6) M completely inhibited the pseudo ChE activity in rat plasma and cortex without affecting true ChE activity. BW 284C51 at a concentration of 10(-6) M gave a total depression of the true ChE activity in these preparations. In rat plasma, however, a considerable part of the pseudo ChE activity was depressed at this concentration.

Aniline Compounds↗

Evasion of macrophage microbicidal mechanisms by mature sporozoites of Plasmodium yoelii yoelii.

Sporozoites of Plasmodium yoelii yoelii were incubated for 40 min with BALB/c peritoneal macrophages in the presence of nitro-blue tetrazolium (NBT). While immature oocyst sporozoites triggered the macrophage respiratory burst, as visualized microscopically by the localized reduction of NBT to insoluble formazan, 97.6% of mature salivary gland sporozoites did not induce such a response. The macrophage oxidative response was also induced by 82.7% of heat-inactivated and 95.7% of trypsin-treated salivary gland sporozoites. The relationship of these results to the infectivity and immunogenicity of malarial sporozoites is discussed.

Animals↗

Detection of alpha-foetoprotein messenger RNA in human hepatocellular carcinoma and hepatoblastoma tissue.

Alpha-foetoprotein (AFP) synthesis, although repressed in normal adults, is increased in the majority of patients with hepatocellular carcinoma (HCC). We have investigated whether active transcription of the AFP gene may explain raised serum AFP concentrations in patients with HCC and hepatoblastoma by assaying human tumour and non-neoplastic tissue by molecular hybridization for the presence of mRNA encoding AFP. Ten operative HCC and six autopsy HCC specimens, two HCC cell lines, and one hepatoblastoma specimen were examined. Total cellular RNA and poly-(A)+ RNA were extracted and AFP mRNA sequences sought by dot-blot and Northern blot hybridisation to a human cDNA AFP probe. Cellular AFP was localised by avidin-biotin staining. AFP mRNA was detected in 8/10 operative specimens, as well as PLC/PRF/5 nude mouse tumours. Weaker hybridization was detected in 4/6 autopsy specimens. Signals of comparable intensity to that in operative tumours were detected in non-neoplastic tissue of 6 patients. AFP mRNA from nude mouse tumours migrated as a 20S discrete band on agarose gel electrophoresis, whereas a more complex hybridization pattern was evident in human tumours. Positive cytoplasmic immuno-staining for AFP was observed in 4 tumours and 2 corresponding non-neoplastic specimens and in a HCC cell line. In non-neoplastic liver, AFP was localised in cells that appeared dysplastic. Thus steady-state levels of AFP mRNA are detectable in human HCC tissue and surrounding non-neoplastic liver. These findings may prove pertinent to an understanding of the genetic expression of AFP in malignant hepatocytes, and the sequence of events leading to uncontrolled cellular proliferation.

Carcinoma, Hepatocellular↗

Comparative expression of hepatitis B virus antigens in several cell model systems.

In this paper the kinetics of hepatitis B virus (HBV) gene expression were investigated in natural and experimentally transfected cell systems. These systems included four human hepatocellular carcinoma cell lines containing HBV DNA (TONG/PHC, HEp 3B2, PLC/PRF/5 and HA22T/VGH) as well as a mouse and a rat cell line both experimentally transfected with HBV DNA. Comparative results on the kinetics of hepatitis B surface antigen in these cell systems suggested that the S gene in the integrated state is expressed at different levels. No human cell line derived from HBV-associated hepatocellular carcinoma produced hepatitis B e antigen (HBeAg) when medium was concentrated by ultrafiltration. In distinct contrast, the two experimentally transfected cell systems produced e antigen at different levels. When all HBV-containing cell lines were grown as tumours in nude mice, no HBeAg was detected in the serum of these mice inoculated with human hepatocellular carcinoma cell lines, in the tumour homogenates, or in the tumour-derived lines, whereas e antigen was expressed both in vivo and in vitro in the experimentally transfected cell lines. These observations indicate that C gene expression is restricted to transfected cell cultures and this suggests a distinct difference in the mechanisms of HBV gene expression between the two types of in vitro model systems.

Animals↗

Arbovirus infection in a Murray Valley community.

Serum antibodies to Ross River virus and Murray Valley encephalitis virus were measured during 1974-1975 in residents of Echuca, an urban Murray Valley community. A representative group of volunteers was obtained by random selection of households. The prevalence of antibodies to both viruses increased progressively with age. Prevalence was equal in both sexes for both viruses in all age groups, indicating that the risk of infection was mainly determined by geography rather than by personal activities. Antibody levels remained unchanged in the following year when there was no disease activity in the area. The stability of antibody levels permitted retrospective estimates of mean rates of infection. These were approximately 0.4% per annum for both viruses when age was used as the index for years of exposure. With allowance for other factors, the best estimate for both virus infections is probably closer to 1%. The morbidity rate for Ross River virus infection appeared to be low. It is concluded that infection with Ross River virus and with Murray Valley encephalitis-related viruses is endemic in the Murray Valley.

Adolescent↗

Acylcarnitines: drug absorption-enhancing agents in the gastrointestinal tract.

Acylcarnitines were tested as potential absorption-enhancing agents for drugs that are poorly absorbed from the gastrointestinal tract. Urethan-anesthetized Sprague-Dawley rats and conscious Beagle dogs were used. Palmitoyl-DL-carnitine was the most effective acylcarnitine tested, although significant increases in drug absorption were observed with acylcarnitines containing C12 through C18 fatty acid chains. Palmitoyl-DL-carnitine afforded significant increases in the absorption of cefoxitin, gentamicin, cytarabine, somatostatin analogue, and alpha-methyldopa. The response to palmitoyl-DL-carnitine was concentration dependent and reversible within 60-120 min. Histological examination of the intestinal tissue revealed no apparent change in mucosal structural integrity at doses of palmitoyl-DL-carnitine that resulted in increased drug absorption. The acylcarnitines were effective in increasing drug absorption from the small intestine and the rectal compartment of both rats and dogs. The data also demonstrated effectiveness with aqueous and solid dosage forms (Witepsol H-15 suppositories). The data suggest that acylcarnitines may be effective and safe absorption-enhancing agents for a variety of drugs.

Animals↗

New dimensions in board-CEO relations.

Hospitals can vary greatly in the development of board-CEO relations. This article, based on a 1985 American Hospital Association survey of hospital governing boards, examines those differences in four key areas: CEO tenure, performance evaluation, incentive compensation plans, and CEO contracts.

Contract Services↗

New trends in governing board-medical staff relations.

A 1985 survey of hospital governing boards reveals some of the ways in which boards and physicians are communicating and cooperating, from physicians' membership on the board to nonphysician board members' involvement with medical staff committees.

Data Collection↗

How hospitals are fostering effective trusteeship.

More emphasis is being placed on the need for hospitals to establish board development and assessment policies. A 1985 survey of governing boards by the American Hospital Association reveals how many hospitals have continuing education and evaluation programs for their trustees, as well as the tools and criteria they use as the basis for those activities.

Data Collection↗

Effects of isosorbide dinitrate on rheumatic and non-rheumatic mitral regurgitation.

Isosorbide dinitrate was given to seven patients with isolated mitral regurgitation (three cases of rheumatic origin, four non-rheumatic) to assess its hemodynamic effects. The pulmonary capillary pressure, left ventricular end-diastolic pressure, left ventricular end-diastolic volume index, and the aortic pressure were all significantly reduced. The heart rate was significantly increased, while the systemic vascular resistance and the left ventricular contractility index were unchanged. The regurgitant flow increased by an average of 72.2% in the rheumatic group, but decreased by an average of 4.8% in the non-rheumatic group (p < 0.05). The forward cardiac output decreased slightly in both groups, but the difference was not significant (NS). It appears that isosorbide dinitrate has a more detrimental effect on cases of mitral regurgitation of rheumatic origin than on those of non-rheumatic origin. We suggest the difference in the responses is a consequence of the dynamic nature of the regurgitant orifice in the non-rheumatic group and the static nature of the orifice in the rheumatic group.

Journal Article↗

A taxonomic analysis of multihospital systems.

Research to date on multihospital systems has proved largely uninformative, in part because similarities and differences among these organizations have not been addressed systematically. Through numeric classification, this article identifies populations of multihospital systems that share similar organizational attributes. Drawing on McKelvey's classification theory, 16 organizational characteristics of 160 multihospital systems are analyzed using a series of taxonomic techniques, including cluster analysis, multiple discriminant analysis, and analysis of coefficients of variation. Fifteen distinct subgroups of systems are identified and described, and their implications for organization research discussed.

Catholicism↗

Isolation and characterization of a Chinese hamster ovary cell line resistant to bifunctional nitrogen mustards.

A drug-resistant derivative of a Chinese hamster ovary cell line has been generated by chronic exposure to progressively higher concentrations of chlorambucil. The cells exhibit greater than 20-fold resistance to the cytotoxic effects of chlorambucil and comparable levels of cross-resistance to mechlorethamine and melphalan. These drugs all belong to a class of bifunctional alkylating agents which generate DNA cross-links by reaction at the N-7 position of guanine. However, no resistance is observed to several other drugs which possess a similar mechanism of action, to cis-platinum diammine dichloride or to bischloroethylnitrosourea and mitomycin C, which cross-link DNA via the O6 position of guanine. Lack of resistance to vincristine, colchicine, or Adriamycin coupled with the failure of the calcium channel blocker verapamil to reverse the phenotype, indicates that the mechanism of resistance is distinct from that characterized by the multidrug-resistant phenotype. Support for this view comes from the finding that no significant alteration in melphalan uptake could be demonstrated. The phenotype is very stable and has been maintained during 12 months of continuous culture without further selection. A slightly elevated basal level of glutathione is present in the resistant cells, but resistance is not overcome by depletion of intracellular glutathione with buthionine sulfoximine. A cytosolic protein with a molecular weight of approximately 25,000 is constitutively overexpressed in the resistant cells. Although these cells have an abnormal karyotype, no conclusive evidence for any cytogenetic indicator of gene amplification could be detected.

Animals↗

Respiratory and heart rate patterns in infants destined to be victims of sudden infant death syndrome: average rates and their variability measured over 24 hours.

From a prospective study in which 24 hour recordings of the electrocardiogram and respiratory activity (abdominal wall movement) were made on a population of full term infants, 22 recordings were obtained from 16 infants who later were victims of the sudden infant death syndrome. The average heart rate, average heart rate variability, average breath to breath interval, and average breath to breath interval variability over the whole of each recording for the 22 recordings were compared with those from a control group of 324 infants selected at random from the rest of the population. No significance was found in the number of recordings from those infants who suffered the sudden infant death syndrome which lay outside the 5th-95th percentile range of the control group for the four variables studied. In a group comparison no difference was found between the sudden infant death syndrome group and the controls either in terms of the respiratory variables studied or in terms of the average heart rate variability. The results did, however, suggest that there may be a group difference in terms of the average instantaneous heart rate.

Age Factors↗