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Biomedical subjects

R T Jones

Publications and source records attributed to R T Jones.

At least 145 records · Page 8Linked to original sources

Modification of hemoglobin with site-directed bifunctional reagents.

Reaction of deoxy-Hb with the periodate-oxidized derivatives of nicotinamide adenine dinucleotide (o-NAD), phosphoribosyl pyrophosphate (o-PRPP), adenosine triphosphate (o-ATP), glucose-1-phosphate (o-glc-1-P) and nicotinamide adenine dinucleotide phosphate (o-NADP) led to formation of cross-link adducts in varying yields as determined by SDS-polyacrylamide gel electrophoresis. Oxygen equilibrium studies were performed on Hb's cross-linked with o-NAD, o-PRPP and o-ATP. These derivatives were found to have increased oxygen affinity and were cross-linked between the beta chains. Inositol hexaphosphate (IHP) blocked modification by these reagents, suggesting that modification was occurring in the organic phosphate binding site. In addition, it was found that the bifunctional reagent 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) also led to formation of Hb cross-linked between the beta chains, but resulted in a derivative with a dramatically decreased oxygen affinity, properties making it a potential candidate as an Hb-based cell-free blood substitute.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Hemoglobin Chico [beta 66(E10)Lys----Thr]: a new variant with decreased oxygen affinity.

Hemoglobin Chico was discovered in an asymptomatic 3-year-old boy when a mild anemia was detected by a routine blood count. Affected individuals in three generations are also mildly anemic. The abnormal hemoglobin amounts to about 45% of the total. It separates from Hb A by cellulose acetate electrophoresis at pH 8.5 with a mobility similar to Hb J but does not separate in citrate agar at pH 6.2. Stability in isopropanol is slightly decreased. Its structure differs from the normal by the substitution of a threonyl residue for lysyl residue at position 66(E10) of the beta chain. The P50 of the oxygen equilibrium curve of whole blood at 37 degrees C was 38 torr compared with controls of 27 +/- 2 torr. The P50 binding studies of the isolated Hb Chico revealed a unique right shift of the equilibrium curve with an oxygen binding constant (1/P50) about half of normal. The remaining allosteric properties were essentially normal. This significant decrease in oxygen affinity appears to be due to changes in the heme region which result from the substitution of the normal beta 66 lysyl by the threonyl residue.

Anemia↗

Cancer-associated alterations of blood group antigen expression in the human pancreas.

Certain alterations of blood group substance (BGS) expression have been observed in gastrointestinal cancer tissues. However, in the pancreas little is known about BGS expression by normal or malignant tissue. The present immunohistochemical study analyzed simultaneously the expression of A, B, H, Lewisa (Lea), and Lewisb (Leb) antigens in specimens of normal pancreas, chronic pancreatitis, and pancreatic carcinoma (primary and metastatic). In normal pancreas all five antigens were expressed in ducts, ductules, and acini, but not in islets. Acinar cells expressed A, B, H, and Leb in supranuclear cytoplasm, whereas Lea was found mainly on centroacinar cells. Only BGSs that were appropriate for the host's blood type were expressed, except for one case of Lea deletion. BGS expression by chronic pancreatitis tissue closely resembled that by normal tissue. In primary pancreatic cancer two cancer-associated alterations were noted that were not found in either normal pancreas or chronic pancreatitis. Deletion of an expected A, B, H, or Leb antigen occurred in approximately 25% of cases, particularly in more poorly differentiated cancers. Incompatible expression of an unexpected A or B antigen occurred in 33% of cases, regardless of degree of differentiation. Metastatic pancreatic cancers also exhibited BGS deletion and incompatibility. In both primary and metastatic cancers the incidence of incompatible A or B expression was higher in cancers from the United States than in cancers from Japan, but the incidence of BGS deletion was similar between the two countries. It was concluded that deletion of A, B, H, or Leb antigens and incompatible expression of A or B antigens are cancer-associated events in the pancreas.

ABO Blood-Group System↗

Pathophysiology of acute renal failure following living Escherichia coli injection in rats: high-energy metabolism and renal functions.

The energy metabolism of kidney and renal function were studied in rats following an IV injection of living Escherichia coli. Energy charge (ATP + 0.5 ADP/ATP + ADP + AMP) decreased throughout the period studied. Total and ouabain-sensitive Na-K ATPase activity of renal cortex homogenate decreased markedly at 3 hr followed by gradual recovery. Polyulia was seen at 3 and 6 hr followed by oliguria at 12 hr after E. coli injection. PSP excretion test showed a marked decrease throughout the time course. In contrast, creatinine clearance decreased only at 12 hr. From these results, it was clarified that the renal insufficiency following bacteremia occurs in two different stages; the early stage with a high urinary output accompanied by decreased Na-K ATPase activity suggesting deterioration of proximal tubular functions and the late stage with oliguria in which glomerular filtration is severely depressed. In both stages, renal energy metabolism is markedly disturbed.

Acute Kidney Injury↗

Reduced tar, nicotine, and carbon monoxide exposure while smoking ultralow- but not low-yield cigarettes.

An unresolved public health issue is whether some modern cigarettes are less hazardous than others and whether patients who cannot stop smoking should be advised to switch to lower-yield cigarettes. We studied "tar" (estimated by urine mutagenicity), nicotine, and carbon monoxide exposure in habitual smokers switched from their usual brand to high- (15 mg of tar), low- (5 mg of tar), or ultralow-yield (1 mg of tar) cigarettes. There were no differences in exposure comparing high- or low-yield cigarettes, but tar and nicotine exposures were reduced by 49% and 56%, respectively, and carbon monoxide exposure by 36% while smoking ultralow-yield cigarettes. Similarly, in 248 subjects smoking their self-selected brand, nicotine intake, estimated by blood concentrations of its metabolite cotinine, was 40% lower in those who smoked ultralow but no different in those smoking higher yields of cigarettes. Our data indicate that ultralow-yield cigarettes do deliver substantial doses of tar, nicotine, and carbon monoxide, but that exposures are considerably less than for other cigarettes.

Adult↗

Tetrahydrocannabinol content and differences in marijuana smoking behavior.

Changes in smoking behavior in response to a change in marijuana potency were measured in marijuana users. A marijuana cigarette containing 1.2% or 3.9% tetrahydrocannabinol (THC) was smoked on separate days by ten experienced users. Puff volume, duration and number, interpuff interval, inhalation volume and duration were averaged for each cigarette. The high potency cigarettes were smoked with more puffs and longer interpuff intervals, but also with greater inhaled volumes of air, thereby diluting the marijuana smoke.

Adult↗

Additive cardiovascular effects of nicotine and ethanol.

Ethanol and tobacco consumption are commonly associated. Both are risk factors for adverse cardiovascular events. To better understand the interactions, the influence of oral ethanol pretreatment (0.5 or 1.0 gm/kg over 60 minutes) on cardiovascular responses to and disposition kinetics of intravenous nicotine was studied in healthy volunteers. Ethanol increased heart rate, systolic blood pressure, and pressure-rate product in a dose-related manner. Nicotine had additive effects on heart rate and pressure-rate product. It also decreased skin temperature, reflecting cutaneous vasoconstriction, but this effect was antagonized by ethanol. Ethanol did not affect metabolic clearance but increased CLR of nicotine by 25%. Additive cardiovascular effects of ethanol and nicotine could contribute to arrhythmias and sudden death in patients with coronary heart disease. It is unlikely that an effect of ethanol on nicotine metabolism is responsible for increased cigarette smoking while drinking ethanol.

Administration, Oral↗

Causes of preweaning mortality on a large intensive piggery.

Causes of preweaning mortality were examined on a large intensive piggery. Diagnosis was made using comprehensive clinical histories combined with post-mortem data. Two thousand four hundred and twenty-six piglets were born in 238 litters. Pre-parturient and parturient losses were 2.9% and 5.4% of the total numbers of piglets born. Birth to weaning mortality was 11.3%. Among piglets born alive, overlaying was the most frequent cause of death (2.1%), followed by deaths due to diarrhoea (1.7%), anaemia (1.2%), savaging (1.1%) and losses of small weak piglets (0.9%). Most deaths, including stillbirths, were associated with below average birth weight, and two-thirds of all deaths of liveborn pigs occurred within 4 days of birth. Increased litter size resulted in decreased birth weights, an increased percentage of stillborn piglets and mummified foetuses, but duration of parturition was not affected. Stillborn piglets were born late in the litter and after a longer interval between pigs born (interpig interval). Over 70% of deaths due to overlay were in previously healthy piglets, but some were associated with illness of the sow (18%) or both sow and piglet (3%). Savaging was confined mainly to first parity sows and was responsible for 20% of all deaths in these litters. Sixty-two per cent of all piglets with a birth weight of less than 800g were stillborn or died before weaning compared with 18.7% mortality for all piglets. Anaemia in piglets was considered to be due to umbilical haemorrhage. Anaemic piglets had a 36% mortality to weaning compared with 10% for non-anaemic piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Veterinary↗

Hemoglobin Linkoping [beta 36 (C2) Pro----Thr] in a large Finnish family from Astoria, Oregon, USA.

Eleven members of a large Finnish family from Astoria, Oregon were studied because of an erythrocytosis. No abnormality was detected by the usual hemoglobin electrophoretic tests, but an abnormal variant was separated by reverse phase HPLC. All of the affected individuals have an increased oxygen affinity with a P50 for whole blood at 37 degrees C averaging 18 torr. Fifty percent of their hemoglobin was found to have a threonyl residue in place of the normal prolyl residue at position 36 (C2) of the beta globin chain. This abnormality is identical to Hb Linkoping which was recently reported in a Finnish man living in Sweden.

Aged↗