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Biomedical subjects

R T Jones

Publications and source records attributed to R T Jones.

At least 181 records · Page 10Linked to original sources
PubMed1984

Involvement of His HC3 (146) beta in the Bohr effect of human hemoglobin. Studies of native and N-ethylmaleimide-treated hemoglobin A and hemoglobin Cowtown (beta 146 His replaced by Leu).

The involvement of the COOH-terminal histidines of the beta chains of human hemoglobin in the allosteric mechanism of oxygen binding has been the topic of intensive discussion. Data presented here on the functional properties of native and chemically modified forms of Hb Cowtown (beta 146 His replaced by Leu) suggest that approximately half of the alkaline Bohr effect is attributable to the imidazole of His HC3(146) beta. The contribution of this residue to the alkaline Bohr effect has been estimated variably as 40-60% and 15% or less. Equilibrium and kinetic studies show that the amino acid substitution in Hb Cowtown decreases the stability of the low affinity conformation, resulting in an increased oxygen affinity and altered sensitivity to anionic effectors. Detailed analysis of Hill plots of oxygen binding according to the Adair scheme reveals that, under conditions of moderate ionic strength (chloride = 0.1 M), the K2 and K3 values for Hb A and Hb Cowtown differ, whereas the K1 and K4 values are closely similar over the physiological pH range. The decreased pH sensitivity of Hb Cowtown is associated with a decreased pH sensitivity of K1, the first Adair constant. In contrast to des-His(146 beta) hemoglobin, the cooperative interactions shown by Hb Cowtown under conditions of moderate ionic strength are not reduced in comparison to those of Hb A. This and the similarity of K1 and K4 values for Hb A and Hb Cowtown indicate that under these conditions the salt bridge formed by the COOH-terminal imidazole group does not significantly contribute to the free energy difference between "T-state" and "R-state" hemoglobin. It appears that the salt bridge formed by the COOH-terminal carboxyl group stabilizes the deoxy, T-state, conformation to a greater degree than previously appreciated. Chemical modification of the Cys(93 beta) residue of Hb Cowtown with N-ethylmaleimide causes a decrease in its oxygen affinity, in contrast to the increase in affinity exhibited by N-ethylmaleimide-modified Hb A. Hemoglobins A and Cowtown have remarkably similar oxygen binding properties after this modification and are shown to have K1 and K4 values distinctly different from those of unmodified Hb A. The properties of native and chemically modified forms of Hb Cowtown are indicative of a large contribution of the His HC3 (146) beta residue to the alkaline Bohr effect and also illustrate how chemical modifications or changes of strategic amino acid residues can result in pronounced differences in the conformational equilibrium of an allosteric protein.

Ethylmaleimide↗
PubMed1984

Trazodone-oral cocaine interactions.

Depression and dysphoria can follow the long-term use of cocaine. Little is known about the interaction of antidepressant drugs with cocaine and similar stimulants in humans. The physiologic and subjective effects of an oral 2-mg/kg dose of cocaine hydrochloride were measured in eight healthy cocaine-using men after pretreatment with a single, 100-mg oral dose of the triazolopyridine antidepressant trazodone hydrochloride or placebo in a double-blind study. The cocaine-induced effects of increased BP, increased pupil size, and decreased skin temperature were diminished by trazodone pretreatment. Trazodone alone did not alter plasma epinephrine or norepinephrine levels. An increase in plasma epinephrine levels after cocaine administration was not altered by trazodone pretreatment, but the increase in the norepinephrine level was larger. Trazodone alone produced mild sleepiness. Cocaine-induced euphoria was not altered by trazodone pretreatment, although feelings of tension and shakiness after cocaine administration were diminished.

Administration, Oral↗
PubMed1984

Cytological studies of carcinogen-treated bovine pancreatic ductal organ explants.

In order to develop a model to study cytological alterations in human pancreatic cancer, we have exposed bovine pancreatic ductal organ explants to a single dose of 2.5 micrograms per ml of N-methyl-N-nitroso-N'- nitroguanidine (MNNG). At serial time intervals, contact cytology smears of the explants were prepared and stained with the Papanicolaou stain. Control samples contained classic tall columnar and cuboidal ductal cells. Cells were uniform in size, shape, staining characteristics, and nuclear morphology. Ductal explants exposed to MNNG progressed through a series of dysplastic and atypical stages during the first 5 to 12 days in culture. Chromatin became increasingly more granular and nucleoli increased in both number and size. Exposed cells were larger than controls and had many dysplastic features. From day 15 to 30, the cells underwent changes morphologically consistent with those of human pancreatic adenocarcinomas .

Adenocarcinoma↗
PubMed1984

The immunoglobulin response of swine following experimental infection with Leptospira interrogans serovar pomona.

The antibody response of pigs following experimental infection with Leptospira interrogans serovar pomona was examined using enzyme immunoassay (EIA) and the microscopic agglutination test (MAT). Leptospires elicited the production of both IgM and IgG classes of antibody, with IgG levels persisting for much longer than IgM. A comparison of MAT and EIA indicated that the detection of specific IgM by EIA was potentially useful in distinguishing between past and recent infection in pigs. Agglutinins were also detected in the urine of infected animals but these antibodies could not be detected by EIA.

Animals↗
PubMed1984

Blood cotinine levels as indicators of smoking treatment outcome.

Pretreatment blood cotinine levels, expired carbon monoxide levels, and self-reported cigarette consumption were evaluated as predictors of smoking treatment outcome in 114 patients. Of these indices of nicotine intake, blood cotinine level was the most useful predictor. High blood cotinine level was the best predictor of dropping out before completion of treatment and of smoking at the end of treatment and at follow-ups. The usefulness of cotinine as a marker of tobacco dependence is discussed.

Adult↗
PubMed1984

Outbreak of botulism in horses.

An outbreak of nervous disease in Standardbred horses occurred near Bendigo, in south-eastern Australia, in October 1980. Over a two week period 11 horses in four training stables were affected with gait abnormalities, depression and recumbency. Eight of the 11 died. The results of an investigation implicated Clostridium botulinum toxin as the cause. The toxin was food-borne as a contaminant of oaten chaff.

Animal Feed↗
PubMed1984

Separation of the tryptic peptides and cyanogen bromide fragments of the human embryonic zeta chains of hemoglobin in Portland I and II by reverse phase high performance liquid chromatography.

The amino acid compositions of tryptic peptides and cyanogen bromide fragments of the purified zeta chain of Hb Portland I (zeta 2 gamma 2) and Hb Portland II (zeta 2 beta 2) have been determined. The hemoglobins were obtained from blood from neonates with hydrops fetalis due to homozygous alpha-thalassemia. The globin chains, tryptic peptides and cyanogen bromide fragments were all separated by reverse phase high performance liquid chromatography (HPLC). Several different types of C-18 columns were used with two different developer systems. The tryptic peptides of aminoethylated zeta chain were separated using an ammonium acetate-acetonitrile gradient. An aqueous trifuoroacetic acid-1-propanol developer gradient was used for the separation of cyanogen bromide fragments. Of the seventeen tryptic peptides obtained, two (zeta T10a and zeta T10b) resulted from the unusual cleavage of a Tyr-Ile peptide bond. This was observed even when using TPCK treated trypsin. From this study and results of others, it can be deduced that trypsin will hydrolyze the Tyr-X bond provided either Ala or Ile is bonded to the N-terminal side of Tyr and Ile, Leu, or Gly is bonded to the C-terminal side of the Tyr residue.

Amino Acid Sequence↗
PubMed1984

Marijuana. Health and treatment issues.

Intermittent use of low-potency cannabis is not generally associated with obvious toxicity. In recent years, some cannabis users have been using high doses more frequently and seeking treatment. A large but incomplete literature indicates that cannabis can be harmful to health, and that virtually every system in the body is affected by cannabis. Cannabis pharmacology is complex; all recent scientific groups reviewing cannabis conclude it is clearly capable of causing adverse effects to health. Specific treatment procedures have not been developed for managing cannabis related problems. Strategies useful in treating other drug dependence problems are useful in treating dependence.

Brain↗
PubMed1984

Degradation of zymogen granules by lysosomes in cultured pancreatic explants.

Pancreatic explants from Syrian hamsters were maintained in culture for determination of the fate of the zymogen granules in the acinar cells. By 6 hours of culture the zymogen granule matrix in many cells becomes nonhomogeneous, and electron-lucent spaces appear. Autoradiography performed 48 hours after pulse labeling shows that several of the altered zymogen granules contain radioactively labeled proteins. Hence these altered granules are mature zymogen granules undergoing regression. Ultrastructural analyses indicate that the zymogen granules are degraded intracellularly in the lysosomes by autophagy, by direct fusion between the lysosomes and the zymogen granules, as well as by engulfment of intact zymogen granules by the lysosomes. Budding of cytoplasm into zymogen granules is also frequently observed. Acid phosphatase histochemistry and anti-amylase immunohistochemistry were used for demonstration of presence of hydrolases and of secretory material in the degenerating zymogen granules. Cycloheximide and low temperature inhibit the degradation of zymogen granules and enhance the short-term viability of the explant. Secretagogues stimulate secretion but have little or no effect on the degradation of zymogen granules or on explant viability. The lysosomes participate in the intracellular degradation of zymogen granules in acinar cells of pancreatic explants. The induction of these lysosomal catabolic processes correlates with the structural alteration of pancreatic acinar cells. The intracellular degradation of secretory membranes and products by the lysosomes may play a role in the adaptation of pancreatic acinar cells to injury.

Acid Phosphatase↗
PubMed1983

Smokers of low-yield cigarettes do not consume less nicotine.

Advertisements suggest that smokers of cigarettes low in nicotine are exposed to less nicotine and tar. Nicotine yields are measured with smoking machines, but machines do not smoke cigarettes as people do. We therefore measured the actual nicotine content of commercial cigarettes with different nicotine and tar yields as determined with smoking machines, and also measured actual nicotine intake as indicated by blood concentrations of its metabolite, cotinine, in 272 subjects smoking various brands of cigarettes. We found that low-yield cigarette tobacco did not contain less nicotine; in fact, the nicotine concentration in tobacco inversely correlated (r = -0.53, P less than 0.05) with the concentration measured by smoking machines. Blood cotinine concentrations correlated with the number of cigarettes smoked per day but not with the nicotine yield measured by smoking machines. Only 3.8 to 5.0 per cent of total variance in blood cotinine was contributed by nicotine yield. We conclude that smokers of low-nicotine cigarettes do not consume less nicotine.

Adult↗
PubMed1983

Separation of zeta (zeta) and various gamma (gamma) chains of human embryonic hemoglobin Portland I by reverse-phase high-performance liquid chromatography.

The zeta (zeta) and various gamma (gamma) chains of Hb Portland I have been separated and isolated from blood samples obtained from neonates with hydrops fetalis due to homozygous alpha-thalassemia. By using developers containing acetonitrile, methanol, and potassium phosphate and either an analytical (3.9 mm x 30 cm) or a preparative (7.8 mm x 30 cm) muBondapak C-18 column (Waters), globin chains from 200 micrograms to 5.0 mg have been isolated in pure forms. Analytical and preparative procedures using short (50-min duration) and extended (186-min duration) gradient programs have been developed. In addition to the type of column and developer conditions, the following factors are found to be important: (a) preparation of sample, (b) sample loading, and (c) cleaning of the column. Preliminary studies indicate that the yield ranges from 40 to 60% depending on the type of globin sample and the age of the column. This procedure also permits the separation of alpha, beta, and various gamma globin chains from fetal and adult samples.

Chromatography, High Pressure Liquid↗
PubMed1983

Organ explant culture of adult Syrian golden hamster pancreas.

An organ explant culture system has been developed for long term maintenance of adult pancreatic tissue from the Syrian golden hamster. Gastric and duodenal lobe explants of up to 0.5 cm2 size were placed in tissue culture dishes (60 mm2) on Gelfoam sponge rafts to which was added 5 ml of CMRL medium 1066 supplemented with heat inactivated newborn bovine serum, L-glutamine, hydrocortisone, insulin, and antibiotics. Dishes were placed in a controlled atmosphere chamber, which was gassed with 45% O2, 50% N2, and 5% CO2 and incubated at 36.5 degrees C. Viability of the tissues was determined by light and electron microscopy as well as by [3]thymidine incorporation. Explants were viable for up to 70 d. Zymogen granule-containing cells characteristic of acinar cells and mucus-containing cells characteristic of ductal cells were present throughout this period. However, endocrine cells were only present for the 1st wk in culture.

Animals↗