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Biomedical subjects

J Holland

Publications and source records attributed to J Holland.

At least 109 records · Page 6Linked to original sources

DNA damage by 8-methoxypsoralen plus near ultraviolet light (PUVA) and its repair in Escherichia coli: genetic analysis.

Mutants of Escherichia coli, hyper-resistant and sensitive to 8-methoxypsoralen plus near ultraviolet light (PUVA) have been isolated and studied. Results show that a mutation, located at 57.2 min on the linkage map of E. coli, is responsible for the hyper-resistant phenotype. It is also responsible for the synthesis of a 55-kdal protein in high concentrations. In a wild-type cell the synthesis of this enzyme is inducible by mitomycin C. There are indications that the mutation may have occurred in a regulatory gene, puvR, and as a result the operon, including a putative puvA gene (the structural gene for the synthesis of the 55-kdal protein), is expressed constitutively. A model for the control of the PUV operon is proposed.

Bacterial Proteins↗

Delirium in cancer patients.

Delirium is the second most common psychiatric diagnosis among hospitalized elderly cancer patients. A variety of factors are known to cause delirium in cancer patients, and the most frequently observed are outlined. History, presence of an altered mental state with identification of the cognitive impairment, and a close watch of mental function will help to differentiate delirium from a normal stress reaction, an adjustment disorder to cancer diagnosis, or early dementia. As in other medically ill patients, antipsychotic drugs are the cornerstone of treatment for delirium not manageable with environmental manipulation or causal therapy. Haloperidol is the most commonly prescribed drug for delirium in the cancer setting because of its low cardiovascular and anticholinergic effects. Cancer patients who are debilitated require a much lower starting dose than do the physically healthy.

Aged↗

A community response to elder abuse.

The 1987 amendments to the Older Americans Act of 1965 required that State Offices on Aging identify agencies involved in identifying and treating abused, neglected, and exploited elders and determine the need for appropriate services for such individuals. This paper discusses how the Dallas, Texas Area Agency on Aging met this requirement and what the community did to increase services for those in need. The creation of an Elder Abuse Task Force had a radiating impact on state law, the statewide adult protective service system, and regional policymaking bodies.

Aged↗

Fade and tachyphylaxis of gastric acid secretory response to pentagastrin in rat isolated gastric mucosa.

1. Gastric acid secretory responses to pentagastrin were characterized in the rat isolated gastric mucosa. In particular, the mechanisms underlying fade, declining response upon continued stimulation, and tachyphylaxis, progressively reduced responses upon repeated stimulation, were investigated. 2. Pentagastrin, 10(-9)-10(-7) M, resulted in concentration-related increases in acid secretion, with a mean maximum of 2.65 mumol cm-2 h-1 in response to pentagastrin, 10(-7) M. Higher concentrations of pentagastrin produced sub-maximal secretory rates; we define this as auto-inhibition. The responses to all concentrations of pentagastrin demonstrated fade. The rate of fade was correlated with the maximum acid secretory rate, declining at about 36% of the peak over the first 16 min. 3. The PO2, PCO2, [HCO3-], pH, [glucose], [lactate], [Na+] and [K+] did not decline during the fade of the acid secretory response to pentagastrin, 10(-7) M. Addition of a second aliquot of pentagastrin was not able to reverse fade, but these tissues were responsive to histamine. Replacement of the serosal solution, before addition of a second aliquot of pentagastrin, increased the acid response from 3% to 24% of the first response. 4. Serosal solution from donor tissues, allowed to respond to pentagastrin and then the acid secretion to fade, was able to stimulate secretion in fresh recipient tissues, although at lower rates. 5. Acid secretory responses to a second dose of pentagastrin were not significantly different, whether the tissues were previously unstimulated, or stimulated with pentagastrin washed out after attaining its peak secretory response (after 10-20 min). The second response was significantly reduced if the first response was allowed to fade with the pentagastrin in contact for 100 min; i.e. fade significantly influenced the extent of tachyphylaxis. 6. Proglumide, 10(-2) M, a gastrin receptor antagonist, and omeprazole, 10(-5) M, an inhibitor of the gastric (H+ + K+)-ATPase, both inhibited pentagastrin-stimulated acid secretion to similar extents. The second response to pentagastrin after pentagastrin alone, or pentagastrin plus omeprazole were both reduced compared to responses after no stimulation or omeprazole alone, respectively. After pentagastrin plus proglumide, the second response to pentagastrin was not lower than after proglumide alone. Proglumide, but not omeprazole, therefore, prevented pentagastrin tachyphylaxis. 7. It is concluded that gastrin fade and tachyphylaxis are related phenomena. Part of the fade may be due to release of an inhibitor(s). The major proportion of tachyphylaxis is a result of specific interaction of gastrin with its receptors.

Animals↗

Human epithelial teratocarcinoma cells (P3): radiobiological characterization, DNA damage, and comparison with other rodent and human cell lines.

Survival parameters and immediate DNA damage induced by 60Co gamma rays, 50-kVp X rays, and Janus fission-spectrum neutrons in human epithelial P3 cells (derived from an embryonic teratocarcinoma) are compared with those for Chinese hamster lung V79 cells. DNA damage caused by X and gamma irradiation, measured by alkaline elution methods, is the same in both cell types, whereas the P3 cells are about two times more sensitive (as measured by Do ratios of the final survival curve slope) to the lethal effects of these radiations than are the V79 cells. Human P3 cells are also more sensitive to the lethal effects of fission-spectrum neutrons than V79 cells. Survival experiments with split radiation doses and hypertonic salt treatment indicate that both P3 cells and V79 cells can recover from radiation-induced damage efficiently.

Animals↗

Psychosocial aspects of head and neck cancer.

The major psychosocial issues in managing the patient with a head and neck tumor are dealing with the emotional reactions to structural and functional deficits, recognizing and treating preexisting personality problems, especially those related to alcohol and tobacco abuse, which frequently complicate their treatment course. These factors influence the rehabilitation process which should begin in the preoperative period with careful attention to psychologic and social assessment and psychiatric evaluation; if an alcoholic history is elicited. Important continuity in rehabilitation can be accomplished by contact with the rehabilitative team members before surgery, preoperative chemotherapy or radiation. Attention to appropriate adaptation to facial prostheses and dealing early with communication disorders requires a specialized staff and a rehabilitative team which can call on a range of skills including a psychiatric consultant. While the ordeal of the head and neck cancer patient is psychologically difficult and challenging, most patients are able, with the proper help, to resume full and productive lives.

Alcoholism↗

Echocardiographic left ventricular mass and physical activity: quantification of the relation in spinal cord injured and apparently healthy active men.

To assess the relation of echocardiographic left ventricular (LV) mass to reported physical activity, 2 groups of subjects with widely different physical activity levels were evaluated: 50 men with spinal cord injuries and 166 apparently healthy, active men. Multivariate analysis revealed that reported physical activity was a significant independent predictor of LV mass index (LV mass/body surface area) in both injured patients and healthy, active subjects after controlling for age and blood pressure. The relation between LV mass index and physical activity (linear regression) was similar for both groups; LV mass index = 0.00321 (physical activity) + 82.8 and LV mass index = 0.00335 (physical activity) +88.4 for patients and healthy active subjects, respectively. These results suggest that physical activity as assessed by self-report is associated with echocardiographically detectable differences in LV mass in groups with widely divergent physical activity levels. In addition, for each of these groups 1,000 kcal/week of physical activity apparently results in a change of approximately 3 g/m2 in LV mass index. This information may have practical use for correction of LV mass for the effects of physical activity.

Adult↗

Inhibition of protein synthesis in developing mouse brain after fission neutron irradiation in utero.

Previous investigations showed that when pregnant mice were exposed to a single whole-body dose of 0.5 Gy fission neutrons on Day 17 +/- 2 of gestation [H. H. Vogel, Jr. and S. Antal, Radiat. Res. 98, 52-64 (1984)] about 40% of the newborn mice died and the body and brain weights of surviving animals decreased by 30-35%. Decreases of body and brain weights were most prominent by the third week after birth, but the content of nucleic acids related to wet weight did not change in liver and brain upon irradiation [S. Antal, A. Fónagy, Z. Fülöp, E. J. Hidvégi, and H. H. Vogel, Jr. Int. J. Radiat. Biol. 46, 425-433 (1984)]. Studies presented in this paper show that after a single whole-body dose of 0.5 Gy neutron irradiation on Day 18 of pregnancy protein synthesis decreased in liver and brain of 3-week-old mice irradiated in utero. Incorporation of labeled amino acids in vivo into acid soluble nuclear proteins decreased by 15% in liver and by 40% in brain. It was significantly reduced into brain histones and certain brain nonhistone proteins (separated by two-dimensional electrophoresis). The amount of H1 and H4 brain histones decreased as well. Investigations with isolated protein synthesizing systems proved that the peptide bond formation was not impaired by irradiation. The aminoacylation of transfer-RNA, however, decreased in both liver and brain by 26-34 and 34-41%, respectively. Comparing the aminoacylation capacities in the two unirradiated organs, a much lower (about one-third) capacity was found in brain than in liver. Moreover, this low aminoacylation capacity of brain decreased further by about 40% after neutron irradiation. These results suggest that in the developing irradiated brain the reduced capacity of aminoacylation of transfer-RNA might be rate limiting for the efficiency of protein synthesis.

Amino Acids↗

The effects of iodination on the receptor binding affinity of ovine prolactin.

A completely iodinated form of ovine prolactin was prepared using lactoperoxidase. The iodination was characterized using gel filtration, electrophoresis and fluorescence analysis. Complete iodination corresponds to a 33% decrease in intrinsic tryptophanyl fluorescence (275 parallel 348). Each ovine prolactin molecule possesses four iodination sites which cannot be distinguished by kinetic analysis. The receptor binding capacity of the tetraiodoprolactin was also assayed using the particulate fraction from female rat livers. Although the total binding capacity of native and iodoprolactins is indistinguishable, significant differences in receptor binding behavior were observed.

Animals↗

The Potter sequence: a clinical analysis of 80 cases.

Eighty cases of Potter sequence due to a renal or urologic abnormality were studied retrospectively. The abnormal renal findings were bilateral renal agenesis in 21.25%; cystic dysplasia in 47.5%; obstructive uropathy in 25%; and others in 5.25%. Fifteen patients had multiple congenital anomalies; of these three had aneuploidy, four had autosomal recessive syndromes, and eight were of unknown cause. Results of chromosome analysis in 41 patients and 21 sets of parents were abnormal in three patients, one of whom had a balanced translocation carrier parent; two additional patients and three parents had apparently balanced translocations. There was one recurrence within the study (the first child had bilateral renal agenesis and the second cystic dysplasia). The ultrasound prenatal diagnosis of the renal abnormality was made in eight cases between 18 and 34 weeks. Family histories were suggestive of an autosomal dominant gene disorder with incomplete penetrance in four of 45 families with nonsyndromic bilateral renal agenesis and cystic dysplasia. The evaluation of patients with the Potter sequence should include an examination for nonrenal defects, autopsy, chromosome analysis, and renal ultrasound or urologic evaluation of parents. Ultrasonographic prenatal monitoring of subsequent pregnancies in such families is strongly warranted because of a definite but unknown degree of recurrence risk.

Abnormalities, Multiple↗

Comparison of effect of peptide length and sulphation on acid secretory potency of gastrin in the cat in vivo and in vitro.

The gastric-acid secretory potency of gastrin peptides was investigated in vivo, in conscious cats prepared with gastric fistula, and in vitro, with kitten isolated gastric mucosae. The influence of peptide length on potency was investigated by comparing synthetic human gastrin heptadecapeptide, non-sulphate (shG17ns) with a synthetic gastrin butyloxycarbonyl hexapeptide (G6ns), and the influence of sulphation by comparison of G6ns with its sister sulphated peptide (G6s). When exogenous doses were compared, shG17ns was the most potent peptide (mean exogenous dose for half-maximal stimulation (EDe50) : 0.33 nmol kg-1 h-1), and was 15.8 times more potent than G6ns (EDe50:5.14 nmol kg-1 h-1). This potency ratio was reduced to 9.4 when circulating immunoreactive concentrations of the two peptides were compared (mean circulating concentration for half-maximal stimulation (EDc50) : shG17ns, 201 pM; G6ns, 1890 pM). The greater potency ratio when exogenous doses were compared was due to the greater metabolic clearance rate (m.c.r.) of the shorter gastrin (m.c.r.: shG17ns, 37 ml kg-1 min-1; G6ns, 121 ml kg-1 min-1). In vitro, shG17ns (mean concentration for half-maximal stimulation (EC50) : 1.99 nM) was 2.8 times more potent than G6ns (EC50: 5.57 nM). Sulphation of the hexapeptide increased its potency 3.6-fold when exogenous doses were compared (EDe50 G6s: 1.42 nmol kg-1 h-1). The greater potency of the sulphated peptide appeared to be due to its lower m.c.r. (20 ml kg-1 min-1), and was eliminated when circulating concentrations were compared; potency ratio G6ns: G6s, 1.1. We conclude that the increased potency of short gastrin peptides observed upon sulphation is likely to be due to increased resistance to metabolic clearance. Part of the increased potency observed with increasing peptide length can also be explained by increased resistance to clearance, but the small potency difference in vitro may reflect greater affinity for gastrin receptors.

Animals↗

Delirium in terminally ill cancer patients.

Nineteen patients believed to be in the terminal stages of cancer were evaluated for signs of delirium. Six patients improved; 13 who died during hospitalization were studied until their death. Patients were interviewed three times a week using a delirium scale; medical records also were used to gather data. Eleven (85%) of the 13 patients developed delirium. In most patients, delirium was caused by multiple factors. The authors outline strategies for management of terminal cancer patients with delirium.

Attitude to Death↗