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Biomedical subjects

M A Baker

Publications and source records attributed to M A Baker.

At least 109 records · Page 6Linked to original sources

Selective regulation of brain and body temperatures in the squirrel monkey.

Many panting mammals can cool the brain below body core temperature during heat stress. Studies on human subjects suggest that primates may also be able selectively to regulate brain temperature. We examined this possibility by measuring hypothalamic (Thy) and colonic (Tco) temperatures of unanesthetized squirrel monkeys (Saimiri sciureus) in two different experiments. First, Thy and Tco were examined at four different ambient temperatures (Ta) between 20 and 36 degrees C. Over this range of Ta, Thy was regulated within a narrower range than Tco. In the cold Ta, Tco was lower than Thy; whereas in warm Ta, Tco was higher than Thy. Second, monkeys maintained at 35 degrees C Ta were acutely exposed to cool air blown on the face or abdomen. Air directed at the face cooled Thy more and faster than Tco, whereas air directed at the abdomen cooled Tco and Thy at the same rate. The second experiment was repeated in anesthetized animals with a thermocouple in the right atrium, and the results showed that this brain cooling was not produced by cooling of blood in the body core. These data demonstrate that the squirrel monkey is capable of selectively regulating Thy. Further the results suggest that venous blood returning from the face may be involved in selective brain cooling in warm environments.

Animals↗

Neonate with Down's syndrome and transient congenital leukemia. In vitro studies.

A white female neonate with clinical manifestations of Down's syndrome was found to have a peripheral white count of 74,000/mm3 with 65% blast forms. Bone marrow aspirate revealed 36% blasts. On chromosomal analysis of bone marrow and peripheral blood, two cell lines were found, one with trisomy 21 and another with pentasomy 21. Colony cultures on the patient's bone marrow cells revealed an adequate growth pattern of CFU/GM. Cells were reactive with myeloblast alloantisera. At the age of 3 weeks, peripheral counts were within normal limits as was morphology of the repeat bone marrow aspirate. Chromosome analysis at that time showed complete absence of pentasomy 21 cell line, and repeat cell colony studies revealed normal growth, differentiation, and maturation of CFU/GM. Maternal serum totally inhibited colony growth of the patient's remission marrow and allogeneic blast cells. This serum inhibitor actually disappeared 1 month postpartum. The patient has had no recurrence of blast cells up to the present age of 3 years.

Antigens, Neoplasm↗

Reduction in local recurrence and improved survival in surgically treated patients with small cell lung cancer.

To assess the role of operation in the treatment and prevention of local recurrence in limited small cell lung cancer, we analyzed retrospectively 35 patients undergoing surgical resection for small cell lung cancer between 1976 and 1982. Twenty-eight patients underwent resection for presumed non-small cell histology. Seven later patients had planned combined modality therapy consisting of chemotherapy and prophylactic cranial irradiation followed by surgical resection and irradiation to the primary site. Twenty-four patients received adjuvant postoperative chemotherapy and/or radiotherapy. All patients have been treated and followed up for a minimum of 1 year. There were 19 patients in Stage I and 16 in Stages II and III. In 15 patients, relapse has occurred. The commonest site of first relapse was brain (7/15). Five of these patients had received prophylactic cranial irradiation. In only two patients was there a relapse locally in the hemithorax and/or mediastinum--one with NO disease and one with N1 disease. No local recurrence was noted in six patients with N2 disease. Only two relapses have occurred beyond 1 year--both in brain. In those patients surviving more than 2 years, no relapses have occurred. The median survival time for patients with Stage I disease is 158 weeks and for those with Stages II and III, 92.4 weeks. The median survival time for the whole group is 92.4 weeks with a projected 5 year survival rate of 24%. It appears that surgical resection may help to prevent local recurrence in small cell lung cancer, even in N1 and N2 disease. In our series, projected 5 year survival rates are similar to those seen in the surgical treatment of patients with non-small cell lung cancer. The eventual role of operation in the prevention of local recurrence and improvement in overall survival of limited small cell lung cancer awaits prospective randomized trials.

Adult↗

Phase II trial of the dopaminergic inhibitor pimozide in previously treated melanoma patients.

Pimozide, a potent neuroleptic which inhibits the release of pituitary releasing factors and is an effective dopamine antagonist, was administered to 30 patients with previously treated metastatic melanoma. Six patients were inevaluable because of poor drug tolerance (two), disease progression within 1 week and death within 2 weeks (three), and death from other causes (one). Among the 24 evaluable patients, two had complete response, two had partial response, and two had disease stabilization. Responses were observed in soft tissue, lymph nodes, liver, and lung. Toxic effects consisted of extrapyramidal manifestations in nine patients and malaise in seven. Pimozide has activity in patients with previously treated metastatic melanoma (17% response rate in evaluable patients) and merits consideration of further study in combination regimens.

Adult↗

Intracranial osmoreceptors control evaporation in the heat-stressed cat.

During heat stress, most mammals regulate body temperature by evaporating body water. Dehydrated mammals reduce their evaporative water losses and allow body temperature to rise. The physiological mechanism underlying this inhibition of evaporative cooling in dehydration have remained unclear. We now report that the rate of evaporation in dehydrated, heat-stressed cats is controlled by intracranial osmoreceptors and suggest that these receptors are part of a common central neural osmoreceptive mechanism regulating evaporative heat loss, renal water loss and thirst.

Animals↗

Immunotherapy for remission maintenance in acute myeloblastic leukemia.

Forty-eight patients with acute myeloblastic leukemia in remission were treated with immunotherapy in addition to remission-maintenance chemotherapy. The first 16 patients were treated with weekly BCG and a leukemia cell vaccine (group 1). The next 32 patients were randomly allocated to receive BCG and a leukemia cell vaccine given once monthly (group 2) or BCG given monthly with no leukemia cell vaccine (group 3). There was no significant difference in remission duration or survival between the randomly allocated groups (2 and 3). Comparisons with group 1 are limited by the non-random allocation to this group, but selection bias was unlikely and clinical features were similar in the three patient groups. No significant difference in remission duration or survival was seen amongst the three groups studied. There was no advantage in the addition of leukemia cell vaccine (groups 1 and 2) to BCG alone (group 3) and no advantage to weekly (group 1) versus monthly immunotherapy (groups 2 and 3). Only 7 of the 48 patients achieved a second remission, and 4 of these were short-term partial remissions.

Adult↗

Immunological studies in a double blind randomized trial comparing intrapleural BCG against placebo in patients with resected stage I non-small cell lung cancer.

Immunological data were obtained during the course of a randomized trial comparing intrapleural BCG plus oral isoniazid (INH) with intrapleural saline plus oral placebo after resection of stage I non-small cell lung cancer. Immunological testing with a variety of assays was carried out with good standardization among six collaborating laboratories and with good reproducibility within each laboratory. Those patients with larger tumors tended to have higher initial white cell counts. The percentage of lymphocytes in the differential was greatest in those with non-squamous cancer histology. Otherwise, no associations were found between initial immunologic parameters and baseline variables. The main effect of BCG/INH therapy was to cause statistically significant increases in purified protein derivative (PPD) skin test induration and PPD in vitro blastogenesis compared with controls. Other skin tests and in vitro assays increased more in the saline/placebo control group, but these treatment differences were usually not statistically significant. Initial white count and neutrophil count elevations were found to be associated with increased risk of recurrence. Even after adjustment for treatment and tumor stage, initial neutrophil count elevation was associated with increased risk of recurrence. Surprisingly, a low 29 degrees C T cell rosette index was associated with a decreased risk of recurrence, though the differences were minimal. Serial immunological tests were carried out to evaluate their potential for monitoring disease recurrence. White count elevations continued to be significantly associated with increased risk of recurrence, but more follow-up data are needed before other associations can be assessed.

BCG Vaccine↗

Effect of dehydration on hypothalamic control of evaporation in the cat.

1. Cats were surgically prepared with intracranial thermodes for heating of the hypothalamic thermosensitive area or with venous cannulae for measurement of blood volume and plasma osmolality. They were kept in an environmental chamber in which the ambient temperature was cycled between 25 and 38 degrees C on an 18:6 hr diurnal schedule. 2. Measurements of blood volume and plasma osmolality and of the evaporative response to hypothalamic heating were made during the 38 degrees C phase of the diurnal temperature cycle in animals when they were hydrated ad lib and in the same animals after 72--96 hr of water deprivation. 3. Water deprivation produced a loss of 10% of the body weight, a significant rise in plasma osmolality and a significant fall in blood volume. 4. Hypothalamic heating in hydrated animals generated a highly significant, positive, linear relationship between hypothalamic temperature and evaporative heat loss in every case. 5. In dehydrated animals, the evaporative response to hypothalamic heating was reduced. Rates of evaporation at a given hypothalamic temperature were lower and the slopes of the lines relating evaporative heat loss to hypothalamic temperature were significantly reduced. 6. It is concluded that dehydration reduces the thermal responsiveness of central neural structures controlling evaporation in the cat.

Animals↗

Control of evaporative heat loss during changes in plasma osmolality in the cat.

1. The effects of intravenous infusion of hypertonic saline and distilled water into normally hydrated and dehydrated cats have been examined at both high and neutral ambient temperatures.2. In hydrated cats measurements of body temperature (T(b)) and evaporative heat loss (e.h.l.) show that infusion of 30% saline (1.5 ml./kg) at an ambient temperature of 38 degrees C, lowers e.h.l. by an average of 0.21 W/kg (P < 0.001) and elevates T(b) by 0.43 degrees C (P < 0.01).3. At 25 degrees C alterations in these two parameters were in the same direction, though not statistically different from pre-infusion levels (P > 0.05).4. Infusion of distilled water (15 ml./kg) into dehydrated animals produced significant increases in e.h.l. (+0.35 W/kg, P < 0.001) and reductions in T(b) (-0.45 degrees C, P < 0.001) at 38 degrees C. No significant effects were observed at 25 degrees C.5. Infusion of water into normally hydrated animals at 38 degrees C also significantly increased e.h.l. (+0.13 W/kg, P < 0.05) and insignificantly lowered T(b) (-0.03 degrees C, P > 0.05).6. Local heating of the preoptic hypothalamic area in four animals indicated that hypertonic saline infusion into normally hydrated animals caused a reduction in the slope and displacement to the right of the relationship between hypothalamic temperature and e.h.l.7. Conversely, water infusion into dehydrated animals increased the slope and shifted this relationship to the left.8. These experiments provide evidence for an osmotic interaction in body temperature regulation which acts to alter the responsiveness of the hypothalamus to increasing temperature. This osmotic component may be an important factor in the alterations in thermoregulation seen in dehydrated animals.

Animals↗

Thermoregulatory influences on common carotid blood flow in the dog.

Common carotid blood flow (CCBF) and respiratory water loss (RWL) were measured in dogs resting at ambient temperatures between 25 and 50 degrees C, during hypothalamic heating, and during light and heavy exercise at ambient temperatures of 25 and 35 degrees C. In resting dogs, CCBF varied with the level of RWL. Elevations in CCBF and RWL occurred within seconds of each other during bursts of panting. Mean unilateral CCBF increased from 6.2 ml . min-1 . kg-1 at 25 degrees C to 16.8 ml . min-1 . kg-1 at 45 degrees C, in parallel with increasing RWL. Hypothalamic heating elicited simultaneous elevations in CCBF and RWL, and the level of CCBF was strongly correlated with the hypothalamic temperature. Both CCBF and RWL increased rapidly at the onset of exercise and continued to rise during a 15-min run. Highest rates of blood flow and evaporation occurred during heavy exercise at 35 degrees C. It is concluded that the rate of blood flow through the common carotid arteries in the dog is related to the thermoregulatory needs of the animal, and most of the increased flow occurring during heat stress is destined for evaporative surfaces of the nose, mouth, and tongue.

Animals↗

Characterization of compounds shed from the surface of human leukemic myeloblasts in vitro.

Human leukemic myeloblasts shed glycoproteins from the cell surface during short-term in vitro culture. Shed surface glycoproteins yield a characteristic profile when studied by gel chromatography, isoelectric focusing, immune precipitation, and polyacrylamide gel electrophoresis. Isolation of immunologically active material yields a compound to approximately 75,000--80,000 daltons, with an isoelectric point of 7.6 to 7.9. Various morphological subtypes of acute myelogenous leukemia shed these compounds, but they are most easily obtained from the more differentiated M2 and M4 types as compared to the undifferentiated M1 type. The shed compounds appear to be quantitatively and qualitatively different from compounds shed by other leukemic cells or nonleukemic cells.

Cells, Cultured↗

Hypothalamic control of thermoregulation during dehydration.

Hypothalamic control of thermoregulatory evaporation has been examined in hydrated and dehydrated cats exposed to warm ambient temperatures. Reduction in evaporative cooling during dehydration is associated with increased hypothalamic temperature. Local thermal stimulation of the hypothalamus indicates that the thermosensitivity of hypothalamic systems controlling evaporation is reduced by dehydration. These findings are discussed in relation to control system models of thermoregulation.

Animals↗

Acute myeloblastic leukemia-associated antigens: detection and clinical importance.

Antigenic compounds from the surface of leukemic myeloblasts are shed in vitro on short-term culture. Blast cells radiolabeled by lactoperoxidase iodination release soluble compounds that react immunologically with alloantisera to leukemia-associated antigens. Partially characterized soluble antigens were used to raise heteroantisera in monkeys that are selectively reactive with leukemic myeloblasts and unreactive with nonleukemic cells. Monkey heteroantisera were used to further characterize soluble leukemia antigens. Sera from patients with acute myeloblastic leukemia inhibit the reactivity of the heteroantisera, suggesting that soluble leukemic antigen is released in vivo as well.

Antibodies, Neoplasm↗