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Biomedical subjects

R W Hamilton

Publications and source records attributed to R W Hamilton.

At least 55 records · Page 3Linked to original sources

Control of morphogenesis in Arthrobacter crystallopoiets: effect of cyclic adenosine 3',5'-monophosphate.

The intracellular levels of cyclic adenosine 3',5'-monophosphate (cyclic AMP) were measured at various intervals during growth and morphogenesis in Arthrobacter crystallopoietes. Cyclic AMP levels remained relatively constant throughout growth in spherical cells grown in glucose-based media. Immediately after inoculation of spheres from glucose- to succinate-containing media, a 30-fold increase in intracellular cyclic AMP was detected. This dramatic rise in cyclic AMP preceded the observed change in cellular morphology from spheres to rods. The cyclic AMP level in rod-shaped cells rapidly dropped to a relatively stable concentration during the exponential growth phase. At the onset of stationary phase and rod-to-sphere morphological transition, a second peak of cyclic AMP was observed. Neither of these two peaks was detectable in a morphogenetic mutant that grew only as spheres. The intracellular levels of cyclic AMP in this mutant remained constant throughout exponential growth and decreased slightly during stationary phase. Effects of exogenously added cyclic nucleotides and their derivatives to both parent and mutant cultures were investigated. The data presented indicate that dramatic changes in intracellular cyclic AMP levels occur just before the morphological transitions characteristic of the morphogenetic cycle in A. crystallopoietes. It is suggested that cyclic AMP is a contributing factor in the regulatory phenomenon associated with morphogenesis in this bacterium.

Arthrobacter↗

Liquid membrane capsules for treatment of uremia.

The objective of the program is to use ingested liquid membrane capsules (LMC) as gastrointestinal toxin traps as an adjunct to dialysis. Urea has been selected as the model toxic component to study before expanding the technology to other toxins. Transport across the small intestinal mucosa has been indicated to be adequate. There is no indication of reduction of mucosal transport or damage to the intestinal mucosa over short term but repetitive LMC perfusions. Performance of LMC perfused through Thiry Vella small intestinal loops is as good as in vitro performance and can be predicted. Substantial progress has been made toward developing LMC to perform in the more complex environment of the intact gastrointestinal tract. The demonstration of LMC performance in vivo with intact gastrointestinal tracts, and perhaps some increase in rate of toxin removal, will be required before LMC can be considered practical candidates for clinical use.

Administration, Oral↗

Perfusion therapy for extremity melanoma.

Because of their initial appearance on extremities, malignant melanomas lend themselves to isolated chemotherapeutic perfusions. Perfusion is attractive because one can deliver effective cytotoxic drugs without systemic toxicity. We are reviewing 20 patients treated between 1960 and 1973 with isolated perfusion. Melphalan (L-phenylalanine mustard) was the drug of choice. Eleven of the 20 patients had previous surgical treatment. Three of the 11 patients are still alive from 27 to 72 months postperfusion. Eight died after an average survival time of 33 months. Of the seven patients who underwent perfusion as primary therapy, four patients are alive from 25 to 76 months postperfusion, and three died after an average survival time of 34 months. There is direct correlation between stages and levels of melanoma, and perfusion and prolonged survival time.

Adult↗

Control of breathing in uremia: ventilatory response to CO2 after hemodialysis.

The mechanisms responsible for the transient respiratory alkalosis which follows clinical hemodialysis were evaluated by studying the ventilatory response to carbon dioxide in chronic uremic patients, and in unanesthetized normal and chronic uremic goats. A significant increase in sensitivity to CO2 was found in acidotic uremic patients immediately (within 30 min) following hemodialysis (P less than 0.01). Sensitivity to CO2 returned to the predialysis value within 24 h. Lung volume and maximal breathing capacity were unchanged. A similar increase in sensitivity to CO2 was seen in nonacidotic uremic goats following hemodialysis. In the goats, these changes in sensitivity could not be explained by changes in cerebrospinal fluid acid-base status. Adding sufficient urea to the dialysate to prevent a fall in plasma urea concentration, eliminated this increase in sensitivity to CO2 in both uremic patients and goats. These results suggests that the transient respiratory alkalosis following hemodialysis is due to an increase in the sensitivity of the ventilatory response to carbon dioxide and is a consequence of dialysis-induced osmotic disequilibrium.

Adolescent↗

Somatic-evoked brain responses as indicators of adaptation to nitrogen narcosis.

Two 2-week experimental pressure chamber exposures to nitrogen-oxygen breathing mixtures afforded an opportunity to study adaptation to nitrogen narcosis. Somatic-evoked brain responses induced by electrical stimulation of the median nerve in the wrist were processed on-line with a signal averager. The N1P2 interval was seen generally to be reduced in amplitude as a result of exposure to increased nitrogen partial pressure. Compressions with air were made from sea level and saturation to 200, 250 and 300 ft of sea water (fsw) equivalent (61, 76, and 91m). The decrement was found to be less, for equivalent exposures, in subjects who had been saturated at the pressure of 90 and 120 fsw (27 and 36 m); we interpret this as evidence of a nonspecific "adaptation." Less adaptation was seen from 30 and 60 fsw (9 and 18 m). These results are consistent with performance tests on the same exposures, and with subjective impressions. Saturation with 3 0r 4 atm of nitrogen may permit somewhat deeper diving without serious narcosis, than is possible from sea level.

Adaptation, Physiological↗

Hemodialysis leukopenia and polymorph random mobility-a possible correlation.

In vitro studies of polymorphs exposed to cellulose and polysulfone membranes showed severe impairment in randommobility with the cellulose membrane. In vivo studies with the two membranes showed that profound leukopenia occurred only when cellulose membrane was used. It is suggested that random mobility may have importance in the regulation of peripheral polymorph levels.

Cell Movement↗

Beta-thalassemia in the American Negro.

In Italian patients with high hemoglobin A(2) beta-thalassemia trait, the synthesis of beta-chains of adult hemoglobin in the peripheral blood is approximately one-half that of alpha-chains. In this study the relative rates of beta- and alpha-chain synthesis were determined in 26 Negro heterozygotes and five homozygotes for beta-thalassemia in six families. The beta/alpha ratio of globin synthesis was decreased in only 15 heterozygotes, whereas in the other 11, beta/alpha globin synthesis was in the normal range or was slightly increased. These unusual findings did not appear to be due to the presence of alpha-thalassemia or a hyperactive "normal" beta-allele. This study demonstrates that the beta/alpha ratio of globin synthesis in the peripheral blood is normal in some patients with beta-thalassemia trait. In five Negro homozygotes with relatively mild clinical disease the beta/alpha ratios were similar to those of Caucasians with Cooley's anemia. Further studies are needed to explore the relationship between normal synthesis ratios in many Negro heterozygotes and milder clinical disease in homozygotes in the same families.

Adolescent↗