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Biomedical subjects

R Stone

Publications and source records attributed to R Stone.

At least 199 records · Page 11Linked to original sources
PubMed1990

Causitive toxin(s) in the death of two Atlantic dolphins.

Following the death of two Atlantic dolphins in a lagoon in March of 1989, the Hawaiian fishes in the lagoon were examined as a potential source of toxin(s). This study reports the findings of the causitive toxin(s) involved, utilizing the stick enzyme immunoassay (S-EIA) and the mouse and guinea pig atrium assays. The S-EIA proved effective in screening the toxic fishes (mullet, wrasse, manini, and aholehole). Following extraction, the major toxin was found in the viscera of these fishes, as confirmed in the mouse assay. The most toxic level was shown in the viscera of the mullet (13.2 mouse units/mg of extract). The viscera of the wrasse, aholehole, and manini also showed high levels of the toxic substance. The guinea pig atrium assay showed the presence of a potent Na+ channel inhibitor, characteristic of tetrodotoxin and saxitoxin. The toxin was also demonstrated in low levels in the dolphin liver and gut content and in the sand and algae extracts from the lagoon. This is the first report of this type of toxin in Hawaii.

Animals↗
PubMed1990

Relation of urinary cotinine concentrations to cigarette smoking and to exposure to other people's smoke.

The relation of urinary cotinine measurements to tobacco consumption in smokers and to exposure to other people's smoke in non-smokers was studied in 49 smokers and 184 reported non-smokers attending a health screening centre. The median urinary cotinine concentration was 1623 ng/ml in the smokers and 6.1 ng/ml in the non-smokers. In smokers the average urinary cotinine concentration increased with reported habitual cigarette consumption; in non-smokers it increased with the reported total seven day duration of exposure to other people's tobacco smoke. Cotinine concentrations were approximately three times higher in non-smokers living with a spouse or partner who was a smoker than in those living with a non-smoker; their reported duration of exposure to tobacco smoke was also three times higher. Non-smoking subjects who were exposed to any tobacco smoke and who lived with a smoker reported 70% of their exposure to be at home (56% for men and 86% for women); the men reported more exposure at work than non-smoking men who lived with a non-smoker. This study confirms the relation of urinary cotinine to stated tobacco smoke exposure in both smokers and non-smokers and further validates the use of information on the smoking habits of the spouse or partner as a measure of tobacco smoke exposure in epidemiological studies of non-smokers.

Adult↗
PubMed1990

Age-related cognitive recovery after general anesthesia.

This study was designed to quantify the rate of mental recovery in elderly and young patients after general anesthesia for intraabdominal surgery (cholecystectomy). Forty patients (25-83 yr) were given four tests assessing neuropsychological function once preoperatively and on five occasions postoperatively. Two of the four neuropsychological tests showed impairment in scores in the elderly patients on the first postoperative day (Symbol Digit Modalities Test, P less than 0.004; The Trail Making Test, P less than 0.03). In addition, one of the tests (Symbol Digit Modalities Test) showed a deterioration in the younger patients (P less than 0.05). The changes that did occur in these tests on the first postoperative day reverted to baseline levels thereafter. There were no significant changes in the remaining two tests, the Mini Mental State Test or the Digit Span Test, at any time in either group. We conclude that postoperative mental deterioration is no greater in elderly than in young patients.

Adult↗
PubMed1990

Application of multiple methods to study the immunization programme in an urban area of Guinea.

During 1988-89, studies were conducted to evaluate the immunization system in Conakry, Guinea. The first, a health facility survey, found that health staff screened the vaccination status of only 30% of children who presented for curative care. A sterile syringe and needle were used for less than half of the injections. In the second survey, key informant interviews with vaccinators and health centre chiefs showed that there were minimal lines of communication between health workers and the community, but that health workers did not perceive this to be a problem. Focus group discussions in the community revealed a high level of general knowledge about vaccine-preventable diseases. However, mothers did not know how many vaccinations their children should receive or by what age they should be completed. They complained of long waiting times in health centres, the high costs of vaccination, poor rapport with health workers, and the occurrence of abscesses after vaccination. The final study, a "knowledge, attitudes, and practice" community survey, showed that missed immunization opportunities and inappropriately timed vaccinations reduced potential vaccine coverage by almost 30% among children with vaccination cards. Higher socioeconomic status, delivery in hospital, and whether mothers perceived the vaccinations to be affordable affected whether the child began the immunization series. Once a child had entered the immunization system, completion of the series was determined by the mother's education level, employment status, and experience with vaccination services.

Adult↗
PubMed1990

Multiple hepatic abscesses: cholangiographic changes simulating sclerosing cholangitis and resolution after percutaneous drainage.

A 59-yr-old man developed multiple hepatic abscesses following an episode of diverticulitis. A percutaneous transhepatic cholangiogram (PTC) showed changes typical of sclerosing cholangitis complicated by multiple hepatic abscesses. No biliary tract stones were seen either on ultrasound or PTC. A single drain left in the right biliary tree and a course of intravenous antibiotics resulted in complete normalization within 14 days of the previously involved biliary tree.

Bacteroides Infections↗
PubMed1989

Enhancement of immunotoxin efficacy by acid-cleavable cross-linking agents utilizing diphtheria toxin and toxin mutants.

We have utilized a new class of acid-cleavable protein cross-linking reagents in the construction of antibody-diphtheria toxin conjugates (Srinivaschar, K., and Neville, D. M., Jr. (1989) Biochemistry 28, 2501-2509). The potency of anti-CD5 conjugates assayed by inhibition of protein synthesis on CD5 bearing cells (Jurkat) is correlated with cross-linker hydrolytic rates. The maximum increase in potency of the cleavable conjugates over non-cleavable conventional conjugates is 50-fold and is specific for the CD5 uptake route as judged by competition with excess anti-CD5. The potency of conjugates made from diphtheria toxin and the anti-high molecular weight melanoma-associated antigen (HMW-MAA) is enhanced 3-10-fold by a cleavable cross-linker. However the potency of transferrin or anti-CD3 diphtheria toxin conjugates is only minimally enhanced (2-3-fold). Mutant diphtheria toxins, CRM103 and CRM9, previously shown to express less than 1/100 of the wild type in binding affinity were substituted into these conjugates as probes for possible intracellular toxin receptor interactions. Both mutants were equally as toxic to Jurkat target cells exhibiting 1/700 the wild-type potency. CRM9 non-cleavable conjugates were equally as potent as wild-type conjugates for transferrin and anti-CD3-mediated uptake but not for anti-CD5-mediated uptake where toxicity was reduced 60-fold over the wild-type analog. The cleavable cross-linker enhanced the toxicity of anti-CD5-CRM103 and anti-CD5-CRM9 conjugates, but potency was only 1/10 that of the analogous wild-type cleavable conjugate. These data are consistent with a model in which potentiation of toxicity of the anti-CD5 and anti-high molecular weight melanoma-associated antigen conjugates by the cleavable cross-linker occurs from an enhanced intracellular toxin-toxin receptor interaction that ultimately results in increased toxin translocation to the cytosol compartment. In contrast, these data indicate that the anti-CD3 and transferrin uptake systems do not require this interaction in agreement with previous work (Johnson, V.G., Wilson, D., Greenfield, L., and Youle, R. J. (1988) J. Biol. Chem. 263, 1295-1300).

Animals↗
PubMed1989

Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester.

The treatment of human HL-60 promyelocytic leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcript. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNF mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase A2 blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B4. In contrast, the cyclooxygenase metabolite prostaglandin E2 inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B4 and prostaglandin E2.

Arachidonic Acid↗
PubMed1989

The caregiving role: dimensions of burden and benefits.

Rapidly increasing public expenditures for nursing home care raise the policy question of how to support community care of disabled elderly persons and postpone admissions to nursing homes. It is crucial that research clearly identify the burdens of community caregivers in order to devise appropriate support programs. Data from the Caregiver Survey of the 1982 Long Term Care Survey are used here to understand dimensions of caregiver burdens and benefits, to develop reliable scales, and to identify sources of variation in burden and benefits. Using factor analysis, two dimensions of caregiver burden were identified, including role strain and role conflicts indicated by items comprising Guttman scales. Caregiver characteristics associated with variations in total perceived caregiver burdens, role strain and role conflict include the extent of caregiving work (disabled person's ADL, IADL scores), caregiver resources (age, health status, employment), latent social characteristics (gender), and the need to make adjustments in living (e.g. among employed caregivers, having to change work schedule to care for the disabled person). Caregiver benefits of two types - help with tasks and socio-emotional support - related inversely to objective burden as well as to relationship to the caregiver (spouse/nonspouse, primary caregiver/other).

Activities of Daily Living↗
PubMed1989

Detection of tumor necrosis factor gene expression at a cellular level in human acute myeloid leukemias.

Tumor necrosis factor (TNF) is a Mr 17,000 cytokine produced by macrophages. We have recently demonstrated that TNF is also produced by transformed human epithelial cells. The present studies have examined TNF expression in human myeloid leukemic cells. We have monitored TNF expression at a cellular level using alkaline phosphatase detection of a biotinylated TNF cDNA probe in situ. Using this approach, TNF transcripts were detectable in HL-60 cells induced along the monocytic lineage by phorbol ester but not in uninduced cells. The specific detection of TNF RNA at a cellular level was supported by the absence of histochemical staining in RNase-treated cells and when using biotinylated pBR322 plasmid without insert. These studies were extended to preparations of purified acute myeloblastic leukemia cells. The results demonstrate that TNF is expressed in myeloblasts in eight of nine patients with AML. In each preparation of myeloblasts with detectable TNF RNA, transcripts were present at 89-98% of the cells. The identification of TNF RNA in situ was also associated with the detection of TNF protein in leukemic blasts by indirect immunofluorescence. Moreover, the detection of TNF protein in these preparations of myeloblasts was confirmed by immunoblotting. However, using this approach to examine AML cells before and after purification indicated that TNF expression is induced as a result of the enrichment procedures. Thus, certain populations of purified myeloid leukemic cells are capable of expressing TNF at both the RNA and protein levels.

Cell Line↗
PubMed1988

Maternal serum thyroid antibodies in early pregnancy and fetal Down's syndrome.

Thyroid antibodies were measured in mid-trimester antenatal serum samples from 77 pregnancies affected by fetal Down's syndrome and 385 unaffected control pregnancies. Using a haemagglutination technique, thyroglobulin antibodies were detected in 5.2 per cent of cases (4) and 2.9 per cent of controls (11), and thyroid microsomal antibodies were detected in 22 per cent (17) and 15 per cent (59), respectively. Using an enzyme-linked immunosorbent assay (ELISA) for thyroglobulin antibodies and a cut-off level of 50 KIU/l, positive results were found in 25 per cent of cases (19) and 22 per cent of controls (84). Using an ELISA for thyroid microsomal antibodies and the same cut-off level, the proportions were 52 per cent (40) and 39 per cent (149), respectively. While not statistically significant, the differences were consistent with the previously reported increased levels of thyroid antibody found in non-pregnant women who had had pregnancies associated with Down's syndrome.

Antibodies↗
PubMed1987

Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methyl-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (CCRG 81045; M & B 39831), a novel drug with potential as an alternative to dacarbazine.

A number of 3-alkyl analogues of the experimental antitumor drug mitozolomide [8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H )-one] have been screened against murine tumors in vivo. Only the compounds with a 3-methyl- or 3-bromoethyl group possessed significant antitumor activity against the TLX5 lymphoma. The 3-methyl analogue, 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (CCRG 81045), was investigated further and found to possess good activity, when administered i.p., against the L1210 and P388 leukemias, the M5076 reticulum cell sarcoma, B16 melanoma, and ADJ/PC6A plasmacytoma. The drug was also active when administered p.o. to mice bearing the L1210 leukemia. A daily for 5 days schedule of 100 mg/kg CCRG 81045 produced increases of survival time of treated animals compared to controls of 176 and greater than 235% against the P388 and L1210 leukemias, respectively. In the female C57BL x DBA/2 F1 mouse the 10% lethal dose was 125 mg/kg daily for 5 days. CCRG 81045 was found to undergo mild alkaline hydrolysis and ring fission to form the linear triazene 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide, which is the putative metabolite formed upon metabolic activation of the antitumor drug dacarbazine [5-(3,3-dimethyltriazen-1-yl)imidazole-4-carboxamide]. The half-life of CCRG 81045 at 37 degrees C in 0.2 M phosphate buffer (pH 7.4) was 1.24 h, whereas that of 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide at 25 degrees C was reported to be 8 min (F. H. Shealy and C. A. Krauth, J. Med. Chem., 9:34-37, 1966). The half-life of CCRG 81045 in human plasma in vitro at 37 degrees C was 0.42 h. Pharmacokinetic experiments conducted in BALB/c mice produced plasma profiles of CCRG 81045, administered i.p. or p.o., which showed a rapid absorption phase, elimination half-lives of 1.13 h (i.p.) and 1.29 h (p.o.), and a bioavailability of 0.98.

Animals↗
PubMed1987

ELISA assays for IgM and IgG rheumatoid factors: their clinical correlations during therapy with slow-acting anti-rheumatic drugs.

A longitudinal study of changes in rheumatoid factor levels and their correlations with other clinical and laboratory assessment of disease activity followed 45 rheumatoid arthritis patients during 12 months continuous therapy with gold and penicillamine. Rheumatoid factors were measured by the titred latex assay and by ELISA assays for IgM and IgG rheumatoid factor. The IgM ELISA assay correlated strongly with the titred latex assay and weakly with the IgG rheumatoid factor assay at 0, 6 and 12 months. All showed significant falls with treatment, and ELISA assays were not more sensitive indicators than the latex assay. Correlations of initial rheumatoid factor levels by all 3 assays to 34 other clinical and laboratory assessments showed that only a small number of weak correlations existed; there were more at 6 and 12 months, but still not many. Changes in rheumatoid factor levels over 0-6 months showed no significant correlation to changes in other variables. There were no more correlations with ELISA assays than with titred latex rheumatoid factor. We conclude that ELISA rheumatoid factor assays have no clinically relevant advantage over the titred latex assay when following rheumatoid patients treated with gold or penicillamine.

Arthritis, Rheumatoid↗