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Biomedical subjects

R C Jones

Publications and source records attributed to R C Jones.

At least 127 records · Page 7Linked to original sources

The effects of oestrogen and progesterone on re-excretion of infectious bronchitis virus strain G (correction of strainG) in SPF chickens.

The effects of oestrogen and progesterone on the re-excretion of IB virus strain G in chickens infected at day-old was evaluated in this study. Following infection of the chickens at day-old, the birds were swabbed regularly from the trachea and cloaca until no more virus was isolated from either site. Between 10 and 14 weeks of age oestrogen and progesterone were administered by intramuscular injection to infected or control chickens. An infected but non-hormone injected group was maintained. All the birds were monitored for virus re-excretion and/or increase in serum neutralising (SN) antibody levels during this period of treatment. Similar parameters, and the egg production of these birds were evaluated when they reached their natural sexual maturity. At the end of the experiment, the birds were sacrificed and their internal organs especially the reproductive organs were examined for any pathological lesions. The acute phase of the disease following infection at day-old was typical of IB virus infection in terms of clinical signs and virus excretions from trachea and cloaca [1]. The injected hormones failed to induce virus re-excretion as no virus was isolated during this period. There was no change in the level of antibody during this period either. However, when the hens attained their natural sexual maturity, IB virus was re-excreted by all the birds. Isolations was also more frequent from the cloaca than from the trachea. The SN antibody levels of individual showed no definite pattern to correspond with periods of re-excretion in the birds up to the end of the experiment. The control birds remained normal throughout the period of the study.

Animals↗

Prevention of formation of important mutagens/carcinogens in the human food chain.

Etiological factors for gastric cancer, among others, involve consumption of smoked, salted, and pickled fish of certain types. Their chemical nature is not yet fully established but probably involves diazo phenols, and their formation can be prevented either by omitting the salting and pickling process, or by using vitamins C and E on the food prior to salting, pickling, or smoking. Both preventive approaches would limit the formation of mutagenic and carcinogenic diazo phenols. Sugimura and associates discovered new types of mutagens as heterocyclic amines that are formed during frying or broiling of meats and fish. In rats, these amines induce cancer specifically in organs such as breast, colon, or pancreas, associated with Western-type nutrition where promotional elements such as dietary fat play an enhancing role. Thus, inhibition of the formation of these new carcinogens during cooking would remove the genotoxic components from the diet. Mixing 10% soy protein with ground meat prior to frying prevents the formation of these mutagens presumably by affording a lower surface temperature. More effective is the addition of tryptophan, proline, or mixtures thereof, which specifically blocks the formation of these mutagens/carcinogens, probably by competing for reactive intermediary aldehydes, so that these cannot interact with the normal essential target, creatinine. Thus, we have available practical, yet science-based, mechanistically understood procedures to prevent the formation of carcinogens associated with important types of cancer prevalent in many countries.

Animals↗

Thromboxane and prostacyclin release after endotoxin infusion in the rat.

To determine in the rat whether pulmonary artery hypertension accompanies thromboxane release, we sequentially monitored pulmonary and systemic artery pressures and cardiac output. We measured pulmonary and aortic plasma levels of TxB2 as well as 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in awake unrestrained adult male Sprague-Dawley rats given a single infusion of endotoxin at the relatively high dose commonly administered to this endotoxin-resistant species. At 40 min after endotoxin infusion, both pulmonary and aortic TxB2 and 6-keto-PGF1 alpha levels increased nine-fold and seven-fold above baseline, respectively. In the pulmonary artery, 40 min after infusion, both mediator levels differed significantly from baseline (p less than 0.05), whereas in the aorta, because of marked variance in the response of different animals, only the 6-keto-PGF1 alpha levels achieved significance (p less than 0.05). These changes were associated with a fall in systemic blood pressure and cardiac output, but no demonstrable rise in pulmonary artery pressure (PAP). Despite ultrastructural evidence of vascular injury, these data indicate that in the rat thromboxane and prostacyclin release following a single infusion of endotoxin is not associated with pulmonary hypertension and that increased prostacyclin production may contribute to systemic hypotension.

6-Ketoprostaglandin F1 alpha↗

Carcinogenicity tests of fecapentaene-12 in mice and rats.

Fecapentaenes, a class of direct-acting bacterial mutagens, have been isolated from the feces and intestinal tract of humans on a Western meat-containing diet. Two bioassays to test pure fecapentaene-12 (FP-12) for carcinogenicity were performed. FP-12 in dimethylsulfoxide (DMSO) solution was injected i.p. into newborn ICR/MA mice on days 1, 3, 7, 10, 14 and 21. The mice killed after 21 months had neoplasms in liver, lung, glandular stomach and subcutaneous fibrosarcoma. Intrarectal (i.r.) infusion of FP-12 in an aqueous vehicle into male F344 rats for 71 weeks, and killing the rats after 21 weeks more, displayed no evidence of neoplasia associated with FP-12 exposure. The positive control, N-nitrosomethylurea (NMU), given i.r. as 4 2-mg doses in 2 weeks, as expected, yielded multiple colonic neoplasms in less than 11 months. Fecapentaene may exert its effect in bacteria and in newborn mice through the generation of hydroxy radicals. However, adult rodent and human colon may have adequate biochemical defense mechanisms against low level, even continuous exposures to chemicals like FP-12, and thus be at low risk of neoplasia, as was found.

Adenoma↗

Stimulation of protein secretion in the initial segment of the rat epididymis by fluid from the ram rete testis.

Zone 1A of the ductus epididymidis was perfused with ovine rete testis fluid (nRTF) and modifications of it, and a synthetic medium (sRTF) based on the inorganic composition of nRTF. There was little fluid transport by the duct mucosa and nRTF stimulated protein secretion. The secretagogue activity was not extracted by charcoal, was sensitive to protease digestion and was present in a portion of nRTF with a molecular weight of greater than 10,000. The addition of bovine serum albumin to the sRTF stimulated protein secretion, but not to the same extent as equal amounts of protein in nRTF. Polyacrylamide gel electrophoresis of the perfusates showed that proteins with molecular weights of 19,000 (all rats studied), and 22,000, 30,000 and 60,000 (at least half the rats studied) were secreted into the perfusion fluids as well as some blood proteins, but the pattern of secretion was not affected by the composition of the perfusion fluid.

Animals↗

The cycle of the seminiferous epithelium in the Japanese quail (Coturnix coturnix japonica) and estimation of its duration.

A regular, well defined spermatogenic cycle was found in the Japanese quail by examining thin sections of isolated lengths of seminiferous tubules embedded in epoxy resin to resolve the structure of developing spermatids. The stages of the cycle initially were identified in studies using a preparatory method for fixation which separated adjacent cellular associations. The cycle was divided into 10 stages with relative frequencies (%) of Stages I to X respectively of: 11.9, 14.8, 24.1, 10.3, 8.2, 6.4, 9.4, 5.5, 3.8 and 5.4. The duration of one cycle was 2.69 +/- 0.08 days (mean +/- s.e.m.) as determined by intraventricular injection of [3H]thymidine and autoradiographic examination of the testes 1-4 days later. It was estimated that lifespans were 2.01 days for type B spermatogonia, 3.86 days for primary spermatocytes, 0.15 days for secondary spermatocytes, and 4.54 days for spermatids. The results suggest that the kinetics of spermatogenesis in the quail are fundamentally similar to the pattern in mammals.

Animals↗

Spatial arrangement of the stages of the cycle of the seminiferous epithelium in the Japanese quail, Coturnix coturnix japonica.

The spatial arrangement of the stages of the cycle of the seminiferous epithelium of the Japanese quail was investigated by preparing three-dimensional reconstructions of a seminiferous tubule from each of 3 quails. It was found that the stages were not distributed at random, but were arranged in a wave which spiralled helically along a seminiferous tubule. Adjacent stages in space were always adjacent numbers in the cycle of the seminiferous epithelium. Complete spermatogenetic waves were found in which all 10 stages of the cycle were in sequential order. However, in most waves the sequential order of stages was disturbed by the occurrence of modulations. The area of a cellular association varied from 4600 to 41,600 microns 2 with a mean +/- s.e.m. (3 animals) of 17,902 +/- 2614 microns 2. The number of Sertoli cells involved in an association ranged from 4 to 35, with a mean +/- s.e.m. (3 animals) of 13.5 +/- 2.8. The findings support our earlier suggestion that the kinetics of spermatogenesis in the quail are fundamentally similar to the pattern which has been described for mammals.

Animals↗

A study of a work site health promotion program and absenteeism.

This paper reports on a study of the absenteeism experience of two groups of Johnson & Johnson employees over a 3-year period. Employees at four company sites (n = 1406) where LIVE FOR LIFE, a comprehensive health promotion program, had been introduced, were compared with employees at five company sites (n = 487) without the health promotion program. Analyses of covariance were employed to control for differences between the two study groups with respect to age, gender, job classification (wage or salaried), as well as baseline levels of absenteeism. Adjusted mean levels of absenteeism among wage earners in the LIVE FOR LIFE groups were found to decline over the study period, and were significantly lower (P less than .01) than mean levels for the non-LIVE FOR LIFE wage employees in the final year of the study. No significant differences were found for salaried personnel.

Absenteeism↗

Different sensitivities of Vero cells from two sources to avian reoviruses.

Four strains of avian reovirus were each titrated in two batches of Vero cells (A and B) from different sources and different media recommended for each batch. For each strain, variations in titre were observed under the different cultural conditions. In one case the discrepancy between the titre in A cells with medium recommended for B cells, and B cells with A medium was 2.1 log10. Attention is drawn to the possibility that important differences in sensitivity may exist between batches of Vero cells from different sources and these may be exaggerated by the use of different media.

Animals↗

Biliary lithotripsy.

At Baylor University Medical Center in Dallas, we began performing lithotripsy with the Medstone STS lithotripter for gallstones in January 1988 and in the first year treated 81 patients. Fifty-five of these patients were available for 4-month follow-up. We randomized half of the patients to receive ursodeoxycholic acid for 7 days prior to lithotripsy and gave all of the patients ursodeoxycholic acid after lithotripsy. Only 10.4 percent of the patients who contacted us ultimately proved to be candidates for lithotripsy. Gallstone fragmentation occurred in 95 percent of all patients and in 97 percent of those patients with solitary stones under 20 mm in size. The rate of clearance for solitary stones less than 20 mm in size was 50 percent. Unfavorable effects ascribable to lithotripsy were infrequent. All of the patients had pain before treatment, and one-third complained of biliary colic after treatment. Minor skin bruising which resolved in 1 to 5 days was found in 20 percent of the patients. This study lends credence to the findings of previous studies and demonstrates that lithotripsy combined with bile acid therapy is a useful therapy for cholelithiasis.

Cholelithiasis↗

Characterization of aminoalkylimidazol-4-one mutagens from liquid-reflux models.

A new class of low molecular weight, aminomethylimidazol-4-one (IQ-"like") mutagens have been produced by the reaction of creatinine with the amino acid L-threonine, in liquid-reflux models, mimicking cooking, of diethylene glycol:5% distilled water (2 h at 150 degrees C). Two mutagens, 2-amino-1-methyl-5-propylideneimidazol-4-one (AMPI) and 2-amino-5-ethylidene-1-methylimidazol-4-one (AEMI) were isolated and characterized by UV absorption spectra, mass spectra, and 1H-NMR. The mutagen AEMI was identical to that obtained from the reaction of creatinine with acetaldehyde. These mutagens were positive in all IQ-sensitive Ames tester strains and were not inactivated by acidic nitrosation at pH 1.0. Products displaying mutagenicity were also obtained by refluxing creatinine with other hydroxyamino acids such as L-serine, L-homoserine, and L-4-amino-3-hydroxybutyric acid, and aldehydes such as glyoxal, methylglyoxal, glycolaldehyde, but not formaldehyde. Simple model systems such as creatinine and acetaldehyde may be useful in more clearly defining the exact mechanism of formation of IQ-type mutagens (aminomethylimidazo-quinolines and -quinoxalines) produced during cooking, as well as in screening for potential inhibitors of IQ-type mutagen formation, and elucidating the mechanism of such inhibition.

Chemical Phenomena↗

Dietary beta-carotene in rat models of gastrointestinal cancer.

The effect of dietary beta-carotene (BC) was investigated in models of gastric and colonic carcinogenesis. Male Wistar rats were fed a diet with 0.4% BC during weaning, then 0.2% BC throughout. Cancer in the stomach and small intestine was induced by giving 80 mg/l N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water for 52 wk, but BC failed to affect carcinogenesis under these conditions, although the incidence of gastric adenocarcinoma was reduced slightly. Neoplastic and nonneoplastic lesions in the liver, skin, and pancreas were also present to a similar extent with BC feeding and without BC. Colorectal cancer was induced by six 2 mg intrarectal infusions of MNNG per rat over a 3-wk period, with the rats held another 22 wk without an inhibitory effect by BC. Thus, 0.2% dietary BC failed to influence significantly the development of neoplasia induced by a direct-acting carcinogen in the gastrointestinal tract.

Animals↗

Biliary lithotripsy in the United States.

We have reported the case of a patient whose gallstone was completely fragmented by lithotripsy; all demonstrable particles passed completely within 36 hours. The patient required no analgesics and had no complications from the procedure. This is the first case of gallstones successfully treated solely by a combination of lithotripsy and bile acid therapy in the United States under an FDA-approved IDE protocol.

Adult↗

Growth factor activity in luminal fluids from the male reproductive tract of the ram, rat, tammar wallaby (Macropus eugenii) and Japanese quail (Coturnix coturnix japonica).

Growth factor activity in luminal fluids from the male reproductive tract was assayed by measuring the stimulation of [3H]thymidine incorporation into BALB/c 3T3 fibroblasts. The potency of fluids from the rete testis of the rat, ram, tammar wallaby and Japanese quail was much the same. However, about 90% of the activity in fluid from the rete testis of the rat and tammar was lost during its passage through the epididymis.

Animals↗

Effects of dimethylthiourea on chronic hypoxia-induced pulmonary arterial remodelling and ventricular hypertrophy in rats.

Ischemia, followed by reperfusion and restoration of oxygen to tissues, generates hydrogen peroxide which in turn generates injurious free radicals, particularly hydroxyl. Chronic hypoxia may also result in liberation of free radicals. In rats, chronic hypoxia causes pulmonary hypertension, associated with structural remodelling of pulmonary arteries, polycythemia, and vasoconstriction. We studied in rats the effects of dimethylthiourea (DMTU), a hydroxyl and hydrogen peroxide scavenger, on acute hypoxic vasoconstriction, and on the arterial structure and development of polycythemia after chronic hypoxia (FIO2 0.10 for 10 days, daily DMTU). DMTU did not affect acute vasoconstriction nor polycythemia. It significantly reduced muscularization of alveolar wall and alveolar duct arteries, medial thickening of alveolar wall and preacinar arteries, and right ventricular hypertrophy, suggesting reduction of pulmonary hypertension. However, DMTU caused marked growth retardation in both control and hypoxic rats, an effect not previously described. In other rats a similar degree of growth retardation due to reduced food intake failed to prevent the effects of hypoxia, suggesting that DMTU's effect is not through this mechanism. The results of this study support but do not confirm the hypothesis that free radicals may have a role in the pathogenesis of the arterial structural changes in the microcirculation contributing to chronic hypoxic pulmonary hypertension. However, in view of DMTU's effects on growth, definitive testing of the hypothesis will not be possible until other, less toxic, chronic hydroxyl scavengers become available.

Animals↗

Effects of certain stress factors on the re-excretion of infectious laryngotracheitis virus from latently infected carrier birds.

Experiments were set up to assess the effects of 'natural' and 'artificial' stresses on the re-excretion of infectious laryngotracheitis (ILT) virus in latently infected chickens recovered from the acute phase of the disease. The stresses were rehousing with the addition of ILT-free contact birds, corticosteroid treatment and the onset of lay. The contact birds were also monitored for transmission of the virus from the carrier birds. Rehousing with unfamiliar birds induced ILT virus shedding in one of five birds and there was evidence of transmission from this bird to its mate. The onset of lay had a significant effect on the overall shedding rates of the carrier birds. Nine of 10 birds shed virus after onset of lay compared with only two in the three-and-a-half weeks before, and there was a highly significant increase (P less than 0.001) in the overall number of virus isolations during this period. Corticosteroid treatment did not affect virus shedding. These results may explain some of the apparently spontaneous outbreaks of ILT which occur in the field.

Animals↗

Nutritional toxicology: on the mechanisms of inhibition of formation of potent carcinogens during cooking.

Frying or broiling of meat or fish yields powerful genotoxic carcinogens such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and related amino-imidazo azaarene carcinogens. We have explored the mode of formation and inhibition of production of these carcinogens. Maillard reactions from precursor amino acids, hydroxyamino acids, and simple carbohydrates appear to yield reactive aldehydes that interact with creatinine to produce specific mutagens/carcinogens. The simplest such IQ-like mutagen, 2-amino-5-ethylidene-1-methylimidazol-4-one, was prepared from acetaldehyde and creatinine. The formation of mutagens in laboratory models and during realistic frying of meat was effectively blocked by L-tryptophan, L-proline, and mixtures thereof. The underlying mechanism rests on competition, between the inhibitors containing an indole ring and creatinine, for intermediary reactive aldehydes produced during Maillard type reactions. The inhibition by L-tryptophan, L-proline, and other indoles is effective and can also be implemented practically.

Carcinogens↗