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Biomedical subjects

J Weaver

Publications and source records attributed to J Weaver.

At least 73 records · Page 4Linked to original sources

Partially compensated hypoadrenalism presenting with persistent skin pigmentation.

A 33-year-old female presented in 1966 with striking pigmentation, typical of Addison's disease, and amenorrhea. Endocrine assessment then showed normal basal serum cortisol and urinary hydroxysteroid levels, but serum cortisol did not respond to stimulation with either exogenous ACTH or lysine vasopressin. Steroid replacement treatment was started. Treatment was discontinued by the patient on her own initiative and after some yr she was lost to follow-up. Reassessment in 1986 showed a pigmented patient who had continued in good health. She had a normal basal serum cortisol level with circadian variation. Plasma ACTH levels were high but showed diurnal rhythmicity and suppressed incompletely with 2 mg or 8 mg of dexamethasone/24 h. Plasma aldosterone levels were normal and showed appropriate postural changes, but plasma renin levels were high. This patient has an immunological profile of autoimmune disease with positive adrenal, thyroid microsomal and gastric parietal cell antibodies with a history of a premature menopause which may also be of autoimmune origin. She has been seen over a 20-yr period and despite her appearance still has no biochemical evidence of glucocorticoid or mineralocorticoid deficiency. It is suggested that the patient had compensated hypoadrenalism, with serum cortisol levels maintained in the normal range by high plasma ACTH levels and serum aldosterone levels maintained by high renin levels. The long term result of the high ACTH levels was increased skin pigmentation.

Adrenal Insufficiency↗

An evaluation of volumes and concentrations of lidocaine in human inferior alveolar nerve block.

The purpose of this study was to evaluate, with the electric pulp tester, the anesthetic efficacy of 1.8 ml of 2% lidocaine with 1:100,000 epinephrine, 3.6 ml of 2% lidocaine with 1:200,000 epinephrine, and 1.8 ml of 4% lidocaine with 1:100,000 epinephrine in human inferior alveolar nerve block. Thirty subjects randomly received each of the solutions at three successive appointments. The first molar, canine, lateral incisor, and contralateral canine were tested with the pulp tester at various time intervals up to 55 min. Complete anesthesia was defined as an 80/80 reading with the pulp tester. No significant differences in anesthetic success or failure were found among the three solutions. Potential anesthetic problems (failure, noncontinuous anesthesia, slow onset, and short duration) occurred in 43 to 57% of the molars, in 43 to 60% of the canines, and in 57 to 80% of the lateral incisors. Complete anesthesia in the mandible is a meaningful clinical problem.

Adult↗

Structural characterization of the alpha-glycerol-3-phosphate dehydrogenase-encoding gene of Drosophila melanogaster.

In Drosophila, multiple isoforms of alpha-glycerol-3-phosphate dehydrogenase (sn-glycerol-3-phosphate: NAD+ 2-oxidoreductase, EC 1.1.1.8) are produced in a tissue- and stage-specific manner. To understand the underlying molecular basis of these isoforms, we have sequenced a 5.8-kilobase region of the Drosophila genome that contains the entire Gpdh locus. Primer-extension and RNase protection assays show that the gene consists of eight exons and has a single transcription-start point. RNase protection mapping and comparison of the genomic sequence from three different cDNA clones reveal that three protein isoforms of glycerol-3-phosphate dehydrogenase are produced by alternative processing of 3' exons. Two of the isoforms differ from the third by the addition of either three or ten amino acids to their C-terminal ends. Transcripts corresponding to two of the isoforms are expressed during both larval and adult stages, while the third isoform is produced only in adults.

Amino Acid Sequence↗

Low molecular weight iron from guinea pig reticulocytes isolated by Sephadex G-25 chromatography.

As part of a continuing study of the low MW iron pool, guinea pig reticulocytes were incubated with 59Fe-labeled transferrin, and the reticulocyte hemolysate was chromatographed on Sephadex G-25. 59Fe, in amounts corresponding to that which was in a low MW peak eluting from an Ultrogel column and to that not precipitated by ammonium sulfate, adsorbed to the Sephadex column. The adsorbing 59Fe, on elution from the Sephadex with dilute formic acid, coeluted with phosphate and pentose. When EDTA was added to disrupt the putative iron complex, neither iron nor P adsorbed to the column, supporting the argument that they exist as a compound in the cytosol and adsorb and elute together for that reason. These observations provide additional evidence that P-containing compounds, probably originating as nucleotides, are important components of the low MW iron pool of cells.

Adsorption↗

Iron release from transferrin: synergistic interaction between adenosine triphosphate and an ammonium sulfate fraction of hemolysate.

In previous work we have shown that red cell hemolysates, at neutral pH, will release iron from transferrin; with molecular sieve chromatography, that activity separated into low molecular weight and high molecular weight components, both susceptible to destruction by phosphatases. Thus the possibility that nucleotides might be involved was suggested. We have studied the interaction of adenosine triphosphate (ATP) and an ammonium sulfate fraction of hemolysate with transferrin. ATP, as well as adenosine diphosphate and 2,3-diphosphoglyceric acid, interacts synergistically with the ammonium sulfate hemolysate fraction to promote iron release from transferrin. This activity is not limited to phosphorylated compounds, because citrate shows a similar effect. This activity is not a nonspecific chelating effect, because deferoxamine is without activity. All the synergistic anions labilize transferrin's HCO3. We therefore suggest that they form a non-HCO3 ternary complex with transferrin and iron, and that release of iron from this complex is promoted by a high molecular weight constituent of the hemolysate.

2,3-Diphosphoglycerate↗

Low molecular weight iron in guinea pig reticulocytes.

The low molecular weight iron found in the guinea pig reticulocyte has been partially characterized. On thin layer chromatography it is distinguishable from the iron complexes of a variety of nucleotides, sugars, and amino acids. On paper chromatography it comigrates with a 250-nm absorbing, orcinol-positive material. The eluted count peak contains phosphorus. Approximately 1 microgram of iron is recovered from 1 ml of hemolyzed red cells. Preparation under nitrogen improves recovery of low molecular weight iron, suggesting that the iron is in the ferrous oxidation state.

Animals↗

Guinea pig and human red cell hemolysates release iron from transferrin.

Despite a binding constant of 10(22) L/mol-1, iron is released from transferrin in the reticulocyte. The mechanism of this release is unclear. It has been suggested that iron is released from transferrin in endocytic vesicles that have been acidified. But the carboxy-terminal iron in transferrin is acid stable at the pH apparently achieved in the endocytic vesicle, and is, nevertheless, released. We found that red cell hemolysates, at neutral pH, will release iron from transferrin. With molecular sieve chromatography, the activity is seen to consist of high and low molecular weight components. The activity of both components is susceptible to destruction by phosphatases. The releasing activity of hemolysates can account for about 25% of the iron uptake of a reticulocyte at pH 7; at pH 5.5 (the purported pH of the endocytic vesicle), the releasing activity is sufficient to account for all the iron taken by the reticulocyte.

Animals↗

Pregnancy induced hypertension: evidence for increased cell membrane permeability to sodium.

In a cross sectional study of 137 women of childbearing age (16-40) the effects of normal pregnancy, hypertensive pregnancy, and oral contraceptives on red cell electrolyte content and sodium efflux rates were examined and the results compared with values in a control group of normotensive, non-pregnant women. Efflux rate constants were significantly increased in normotensive pregnancy and in women taking oral contraceptives. This was associated with a significant increase in sodium permeability in the contraceptive group. A much larger increase in sodium permeability and efflux rate constant was seen in the hypertensive group. The results permit a hypothesis that the hormonal changes induced by pregnancy and oral contraceptives increase membrane permeability to sodium and stimulate sodium efflux. The rise in blood pressure associated with use of oral contraceptives may have a similar aetiology to that occurring in pregnancy induced hypertension.

Adolescent↗

Reactivity of mitomycin C with synthetic polyribonucleotides containing guanine or guanine analogs.

The guanine residues in nucleic acids are believed to be the major covalent binding site of the antibiotic mitomycin C. To identify the specific functional group in guanine which reacts with mitomycin C, reactions were run between the antibiotic and poly(G) analogs in which guanine was blocked at the N-7 or O-6 position, or lacked the 2-amino group. Binding ratios were affected to a small extent in the two former cases, but binding was significantly decreased in the absence of the 2-amino group. These results indicate that the most likely binding site of mitomycin C in synthetic polyribonucleotides is the 2-amino group of guanine residues.

Antibiotics, Antineoplastic↗

Failure of chronic administration of the angiotensin I-converting enzyme inhibitor, Teprotide (SQ 20881), to affect the ultrastructure of the adrenal cortex and the aldosterone secretion in the rat.

Administration of Teprotide (SQ 20881), an angiotensin I-converting enzyme inhibitor for up to 10 weeks at a dose of 3 mg. per kg., subcutaneously, twice a day in the rat, effected no change in the ultrastructure of the adrenal cortex nor in the concentration of serum aldosterone. A significant increase (p less than 0.05) in renin granulation indices which was already apparent after 3 weeks of treatment with Teprotide was even more definitive after 10 weeks (p less than 0.01). Moderate renal hypertrophy was present in rats receiving the drug for 3 weeks. Findings pertaining to aldosterone production differed from those reported following acute administration of Teprotide wherein a decrease in the production of serum aldosterone and an increase in plasma renin activity was observed. It has been suggested that decreased aldosterone production following acute administration of Teprotide is a consequence of decreased stimulus of the zona glomerulosa due to diminished synthesis of angiotensin II. If this is the case, mechanisms other than angiotensin II stimulation of the zona glomerulosa must control aldosterone synthesis, perhaps through hormones of the adrenal cortex. Another possibility could be that angiotensin II synthesis may be obtained, after an interval, through an alternative pathway.

Adrenal Cortex↗