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Biomedical subjects

J M Hunt

Publications and source records attributed to J M Hunt.

At least 73 records · Page 4Linked to original sources

Immunological approaches to the purification of putative premalignant hepatocytes from genotypic mosaic rat livers.

Surface-localized rat RT1 alloantigens on isolated hepatocytes have been used to achieve partial purification of putative premalignant liver cells from rats undergoing chemically induced hepatocarcinogenesis. Genotypic mosaic rat livers were constructed by transplantation of carcinogen-altered F-344 (RT1Iv1) or WF (RT1u) donor liver cells into livers of WF X F-344 F1 host rats, whose liver cells bear alloantigens of both parental strains: WF and F-344, RT1u and RT1Iv1, respectively (J. M. Hunt et al., Cancer Res., 42: 227-236, 1982). Donor and host origin hepatocytes were thus distinguishable immunologically with anti-RT1u or anti-RT1Iv1 alloantisera. Donor rats were treated with diethylnitrosamine (200 mg/kg i.p.) followed by an experimental regimen of dietary 2-acetylaminofluorene and partial hepatectomy. Standard host rats received only the 2-acetylaminofluorene-partial hepatectomy regimen. At 10 to 21 days after transplantation, mosaic host rat livers typically contained 7% donor origin hepatocytes, 96% of which were positive histochemically for gamma-glutamyl transpeptidase. Host origin hepatocytes could be effectively purified by affinity chromatography ("panning") of isolated hepatocytes. To obtain donor origin hepatocytes, the putative progenitor cells of liver carcinomas in these mosaic livers, two approaches were used. Alloantibody-mediated rosette formation followed by sedimentation through Ficoll/metrizamide resulted in a 4- to 10-fold enrichment for donor origin hepatocytes isolated from mosaic livers. Similarly, a 5- to 11-fold enrichment for donor origin hepatocytes was achieved by specific alloantibody-mediated cytolysis of host hepatocytes with rabbit complement followed by purification of viable donor origin cells by sedimentation on metrizamide cushions. Hepatocellular carcinomas which developed in the genotypic mosaic host rat livers were excised 17 to 21 months after donor liver cell transplantation and passaged s.c. or i.m. in histocompatible rats. The transplantable tumors were typed for strain of origin by indirect immunofluorescence using rat alloantisera, and five of six tumors displayed antigenicity reflecting donor strain origin. We conclude, therefore, that the transplanted donor liver cell populations contain cellular precursors of hepatocellular carcinomas which may be isolable using combinations of the purification strategies described.

Animals↗

Epidemiology of malignant mesothelioma in Western Australia.

Crocidolite was mined and milled at Wittenoom Gorge in Western Australia from 1943 to 1966. Between 1960-1964 and 1980-1982, the estimated incidence of malignant mesothelioma in Western Australia rose from 0.6/100 000 in men and less than 0.1/100 000 in women, aged 35 years or older, to 6.6/100 000 in men and 0.7/100 000 in women in this age group. Overall, 97 (70%) of 138 patients with malignant mesothelioma had definite or probable exposure to asbestos; 76 of these (55%) to Western Australian crocidolite. Of the latter 76 patients, 56 had worked in the mine or mill at Wittenoom and 4 had non-occupational exposure in the Wittenoom area; the remaining 16 had been exposed to crocidolite elsewhere in the State. There were only 4 (3%) patients with malignant peritoneal mesothelioma, of whom three had been exposed to crocidolite.

Adult↗

Increased ionized calcium and left ventricular contractility during hemodialysis.

Routine hemodialysis is associated with an increase in left ventricular contractility that is independent of a change in preload, but the mechanisms responsible are unknown. We investigated the importance of three distinct effects that regularly occur in hemodialysis and could potentially improve left ventricular contractility: the removal of uremic toxins, the increase in the plasma ionized calcium concentration, and the increase in the plasma bicarbonate concentration. Three different dialysates were used for each of eight stable patients on long-term hemodialysis, and left ventricular contractility was assessed by two-dimensional echocardiography before and after each dialysis. In the first procedure neither the ionized calcium nor the bicarbonate concentration was allowed to increase, and left ventricular contractility did not improve. In the second procedure, ionized calcium increased (from 4.4 to 5.4 mg per deciliter, P less than 0.001), bicarbonate concentration was held constant, and contractility increased (from 0.74 to 0.93 circumferences per second, P less than 0.005). In the third procedure, ionized calcium was kept constant, the bicarbonate concentration increased (from 19 to 24 mmol per liter, P less than 0.001), but contractility did not increase. These results suggest that the increase in ionized calcium that occurs in regular dialysis is a key factor in the improvement in left ventricular contractility observed during the procedure.

Adult↗

Gas exchange during dialysis. Contrasting mechanisms contributing to comparable alterations with acetate and bicarbonate buffers.

Although arterial hypoxemia during hemodialysis is common and may contribute to dialysis morbidity, the mechanisms responsible remain uncertain. Additionally, controversy exists as to whether bicarbonate dialysate produces less hypoxemia than acetate dialysate. The short- and long-term effects of acetate dialysate and bicarbonate dialysate on gas exchange were compared in eight stable patients undergoing dialysis using a closed, proportioning system and a double-blind, crossover study design. Dialysate was sampled immediately proximal and distal to the dialyzer to determine its contribution to total carbon dioxide elimination. Ventilatory parameters and blood gas values were measured before dialysis, at one hour, and after dialysis. Arterial oxygen tension fell significantly and comparably at one hour with both dialysates, whereas the alveolar-arterial oxygen gradient increased only slightly. Despite hypoxemia, minute ventilation decreased by 4 to 18 percent, and arterial carbon dioxide tension was unchanged. Although total carbon dioxide elimination was unchanged in all groups, there was a significant decrease in lung total carbon dioxide elimination with acetate dialysate of 9.23 +/- 2.69 to 7.74 +/- 1.57 mmol per minute on Day 1 (mean +/- SD, p less than 0.025) concomitant with a loss of total carbon dioxide into the bath of 2.04 +/- 0.20 mmol per minute, resulting in a significant reduction in respiratory quotient (0.92 +/- 0.07 to 0.75 +/- 0.05, p less than 0.01). In contrast, there was a gain of total carbon dioxide into the blood of 1.64 +/- 0.45 mmol per minute with bicarbonate dialysate, which resulted in an increased pH at one hour compared with acetate dialysate (7.39 +/- 0.04 versus 7.35 +/- 0.03, p less than 0.05). Hypoxemia persisted after dialysis in all groups and was associated with an increased alveolar-arterial oxygen gradient in three of the four groups. It is concluded that transitory hypoventilation contributes to comparable hypoxemia with both acetate and bicarbonate dialysates by different mechanisms. With acetate dialysate, there is a decrease in carbon dioxide load to the lungs, whereas with bicarbonate dialysate, the mechanism responsible appears to be a suppression of respiratory drive resulting from a gain of bicarbonate from the dialysate. Additionally, neither dialysate prevents post-dialysis hypoxemia, which is associated with an increased alveolar-arterial oxygen gradient resulting from a mechanism that remains to be elucidated.

Acetates↗

DNA adduct formation, removal and persistence in rat liver during one month of feeding 2-acetylaminofluorene.

Male Wistar-Furth rats were fed 0.02% 2-acetylaminofluorene (AAF) for 3 days or 0.02% AAF for 25 days followed by 0.02% [ring-3H]AAF for an additional 3 days. The concentration of hepatic DNA adducts was then monitored by both radioimmunoassay and radiolabeling during 28 days of control diet. This approach allowed comparisons to be made of adduct accumulation, removal and persistence at both the beginning and end of a four week carcinogen feeding period. DNA adduct formation remained constant during the month of AAF administration with an accumulation rate of 157 fmol adduct/micrograms DNA during days 1-3 and days 25-28 of the experiment. Furthermore, the rate of removal of adducts formed during these three day periods was similar when both groups were fed control diets for 28 additional days. Continued AAF administration resulted in a slow accumulation of persistent adducts; thus, 91 +/- 6% of the adducts detected after 3 days of AAF feeding were removed during a subsequent month of control diet, while only 65 +/- 11% of the adducts detected after 28 days of AAF diet were removed when rats were fed control diet for an additional 28 days. In a second experiment, the removal of adducts was compared in animals fed control or AAF diet after previously being fed 0.02% AAF for 17 days. Similar removal curves were observed in both groups; therefore, continued ingestion of AAF did not affect the rate of adduct removal. In both experiments, biphasic repair curves were observed. These data were used to develop a pharmacokinetic model. Two genomic regions were postulated, an area susceptible to fast repair and a region more resistant to the removal of AAF adducts. At equilibrium, which was reached after 2-3 weeks of AAF feeding, the concentration of adducts in each region was similar with approximately 150 fmol adduct/micrograms DNA. Although the total number of adducts formed in the fast repair region during one month of AAF administration was five times greater than in the resistant region, the model predicted that the adducts localized in regions resistant to repair were the persistent adducts detected after one month of control diet. Overall, the removal of adducts formed during chronic AAF feeding was very efficient since greater than 93% of the adducts were removed by the end of a subsequent month of control diet.

2-Acetylaminofluorene↗

Isolation of Campylobacter jejuni from raw milk.

Campylobacter jejuni was isolated from raw milk by a method that can routinely detect less than or equal to 1 organism per ml. This procedure was used in a survey of 195 separate farms and showed a 1.5% incidence of C. jejuni in milk from bulk tanks.

Animals↗

Alloantigen-mediated adherence of rat hepatocytes to antibody-coated polystyrene dishes.

Rat alloantigens expressed on normal hepatocytes have been utilized in a cell "panning" procedure to mediate the haplotype-specific adherence of collagenase-isolated hepatocytes to antibody-coated polystyrene dishes. A polyvalent F344 anti-WF alloantiserum was prepared by immunizing F344 rats with WF tissue. The alloantibody IgG purified from the alloantiserum, when reacted with either WF or (WF X F344)F1 hybrid rat hepatocytes, caused the adherence of these hepatocytes to bacteriological-grade polystyrene dishes coated non-specifically with a xeno-antibody, rabbit anti-rat IgG. Similarly-treated hepatocytes of the F344 strain, which lack WF alloantigenic determinants, failed to be adsorbed above background level to the coated dishes.

Animals↗

Prevention of doxorubicin-induced alopecia by scalp cooling in patients with advanced breast cancer.

Scalp cooling with gel packs was used to try to prevent alopecia in 31 patients being treated with doxorubicin (Adriamycin), 29 for advanced breast carcinoma and two for carcinoid tumour. Twenty-eight of the 31 patients tolerated the procedure well, and 22 of these had either no hair loss or only slight loss which remained acceptable and did not require a wig. The main factor limiting success was biochemical impairment of liver function, which occurred in nine patients; of these, six had severe or total alopecia despite scalp cooling. Conversely, the technique was successful in all 19 patients with normal liver function. Carried out properly, this simple and effective technique greatly diminishes socially unacceptable alopecia associated with doxorubicin, and merits wider use.

Adult↗

The intravenous urogram in acute epididymo-orchitis.

In a series of patients presenting with acute epididymo-orchitis, the abnormalities detected on intravenous urography were analysed. Urography is recommended in patients aged over 50 and in pre-pubertal boys, but it did not prove useful in adult patients under 50 years of age without other symptoms.

Acute Disease↗

Characterization of Vibrio cholerae isolated from oysters.

Of 790 samples of oyster shellstock freshly harvested during a 12-month survey, 111 (most of which were harvested from June through August) contained Vibrio cholerae non-O1 (611 strains), and seven contained O1 Inaba (11 strains) organisms. None of the V. cholerae strains isolated were enterotoxigenic by immunological and biological tests.

Animals↗

Specificity of the Tumor-specific transplantation antigen induced by JC virus, a human polyomavirus.

The specificity of the tumor-specific transplantation antigen (TSTA) induced by JC virus was investigated by cross protection tests in weanling hamsters. Hamsters immunized with JC virus, BK virus, or SV40 were challenged 5 weeks later with known numbers of JC virus- or SV40-induced hamster tumor cells. Both the JC virus-immune and the SV40-immune hamsters showed resistance to challenge with homologous but not heterologous tumor cells, and the BK virus-immune hamsters were not resistant to either heterologous tumor cell. The TSTA induced by JC virus did not cross-react with that induced by SV40.

Animals↗