Elimination of graft versus host disease in matched allogeneic leukemic transplant recipients using CAMPATH-1.
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Biomedical subjects
Publications and source records attributed to S Samuels.
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Severe DF-2 sepsis with disseminated intravascular coagulopathy developed following dog bites in two patients who had undergone prior splenectomy. Eschariform lesions developed at the site of the animal bite in both patients. DF-2 is an unusual animal-borne slow-growing gram-negative rod that can cause fulminant sepsis in splenectomized patients. Splenectomized patients should be aware of the hazards from a dog bite. The presence of eschariform lesions in such patients should provide a clinical clue to the presence of DF-2 infection.
A review of the literature revealed only three cases of long-term psychotherapy of young children in which significant I.Q. gains were reported. A series of ten children is presented who received intensive long-term psychotherapeutic treatment and who obtained a mean I.Q. gain of 27.9 points.
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To study the late effects of early postnatal treatment with N-ethyl-N-nitrosourea (ENU) preceded by X irradiation to the head, 226 neonatal CD rats were divided into six groups which received the following treatment: (1) 500-rad X irradiation to the head on the third postnatal day (pnd); (2) injection ip with 30 mg/kg ENU on the fourth pnd; (3) injection ip with 30 mg/kg ENU on the seventh pnd; (4) a combination of 500-rad X irradiation to the head on the third pnd, followed by ip 30 mg/kg ENU on the fourth pnd; (5) a combination of 500-rad X irradiation to the head on the third pnd, followed by ip 30 mg/kg ENU on the seventh pnd; and (6) untreated controls. The results indicate that (1) X irradiation to the head alone significantly extended the life span of females compared to that of control females, and did not affect survival of males; (2) X irradiation did not influence the latent period or mortality from neurogenic tumors when ENU was given 1 or 3 days afterward; (3) ENU itself was a factor in shortening latent periods for mammary tumors; (4) X irradiation alone did not increase the incidence of mammary tumors, and revealed no protective effect on the ENU-induced mammary carcinogenesis; (5) X irradiation increased the prevalence of pituitary tumors in the females; (6) no enhancement of pituitary tumors by ENU was observed: and (7) there was a statistically significant association of pituitary and mammary tumors in females.
A cluster of ten nosocomial eye infections occurred in three intensive-care units during an 18-month period. Nine of the ten patients were intubated, all were obtunded, and all had copious sputum production. The bacteria isolated from the patients' sputum samples and from the eyes were identical in nine cases. Pseudomonas aeruginosa caused six of the infections, including all those with complications (three corneal ulcers, two hypopyon, one opaque cornea, two corneal rupture). Three patients lost their sight. Only the left eye was infected in nine cases. In a prospective study of bacterial dispersion during tracheal suctioning of twenty intubated patients, patients with copious secretions had significantly higher bacterial colony counts on settle plates than those without. Colony counts were higher on the side opposite to the hand the nurse used to withdraw the catheter than on the same side. Nurses tended to withdraw the catheter diagonally across the patient's face, which may explain the selective involvement of the left eye.
Blood-to-brain amino acid transport consists of at least two components: 1. a fast rate or early process, commonly measured by the intra-carotid bolus injection method and attributed to transport across the capillary endothelium and entry into the astrocytes, and, 2. a slow rate or later component measured over 2 to 15 minutes probably associated with exit from the astrocytes and entry into the neurons. Incorporation into brain protein is temporally related to the second process. In the present study the slow and fast rate transport components and the incorporation into brain protein of tyrosine (Tyr) and Valine (Val) was measured in young adult and aged male C57BL/6 mice. The results indicate that the fast rate transport component is unaffected by age while the rates of the slow process and protein turnover show an exponential decline most marked between 3 and 8 months of age. Changes in the relative incorporation of Tyr and Val suggest that brain protein metabolism is altered qualitatively as well as quantitatively in aging, in these animals.
Knox reported that the short-term effects of the carcinogen methylnitrosourea (MNU) were due to the formation of its decomposition product, the cyanate ion. He showed that cell survival and DNA synthesis decreased as the concentration of MNU and the cyanate ion (NCO-) increased in the medium. Further, the product of MNU decomposition comigrated with NCO- when added to his chromatographic test system. However, Knox did not study the mutagenicity of MNU or its breakdown products. We compared the mutagenicity of MNU and potassium cyanate (KNCO) in mammalian cells. Our results demonstrate that, although it is toxic to cells, KNCO does not induce ouabain-resistant mutants in cultured Chinese hamster cells (V79).
Is silicosis still a serious threat to foundry workers? Medical and epidemiological information has been scant for the past 30 years. However, several recent surveys of silica dust levels in United States foundries give substantial indication of a continuing exposure hazard. The present research effort was aimed at collecting silica dust exposure data in the foundry environment. OSHA industrial hygiene records were collected from foundry inspections in which air sampling of silica-bearing dusts had been conducted. Two hundred and five foundries supplied 1743 personal air samples. The results present a detailed exposure profile of specific work areas, job titles, type and size of foundry. Based on the results of this and other similar studies reported in the past decade, it appears that silica dust continues to be a serious health hazard to foundry workers. If such is the case, then an epidemiological investigation of the industry should be undertaken to determine a prevalence rate of silicosis. Such a study could provide much needed information on the dose-response relation of silica exposure and silicosis, as well as information with which to reevaluate the adequacy of the current TLV for crystalline-free silica.
We have proposed that glutamine serves in a facilitated diffusion process, mediated by the enzyme gamma-glutamyl transferase (gamma-glutamyl transpeptidase; gamma GT) and that it leaves the brain in exchange for entering amino acids. Glutamine is also a precursor of gamma-aminobutyric acid (GABA). Thus, providing an alternate substrate for gamma GT should spare brain glutamine, raise GABA, and cause an anticonvulsant effect. We have found that glycylglycine, the best-known substrate for gamma GT, and delta-aminovaleric acid (DAVA), a structural analog, have anticonvulsant activity in DBA/2J mice. Both compounds can decrease the incidence and severity of seizures induced by L-methionine-RS-sulfoximine or electroconvulsive shock. DAVA was also tested and found to be active against seizures caused by pentylenetetrazol or picrotoxin. [14C]DAVA entered the brain at the rate of 18.7 nmol/g/min. The activity of DAVA as a substrate of gamma GT was intermediate to that of glycylglycine and glutamine. Preliminary studies have shown that brain glutamine and perhaps GABA are elevated 3 h after administration of DAVA (7.5 mmol/kg). These findings support the theory that glutamine exchange plays a role in amino acid transport across the blood-brain barrier and suggests a new concept in anticonvulsant therapy.
Use of vitamin C in food and pills and its association with health habits and health status were investigated in a random sample of 3,119 adults in Alameda County, California. Vitamin C intakes of nearly 80 per cent of respondents met or exceeded Recommended Daily Dietary Allowances. Fourteen per cent or fewer appeared to have inadequate vitamin C intake. Vitamin C supplements were taken daily by 29 per cent, occasionally by 21 per cent. Most respondents obtained 100 mg or less of vitamin C daily; 2 per cent had more than 2000 mg. Proportionately, more women than men took vitamin C pills daily. Men aged 16 to 44 were the most likely to have neither vitamin C foods nor pills. Persons 45 years and older tended to take vitamin C pills daily, younger persons to take them occasionally. Respondents who did not eat breakfast or who smoked cigarettes had lower vitamin C intakes. People in poor health took more vitamin C than those in good health. Health status may have influenced vitamin C intake rather than vitamin C intake influencing health status.
Under steady-state conditions, the transport rates for amino acids from blood to brain have been found to be about half that seen using the intraarterial injection technique. Using a method that mathematically mimics the constant infusion procedure, we were able to reconcile this apparent discrepancy. At less than 1 min after subcutaneous injection of [14C]tyrosine in mice, we have observed a rate of entry into brain of 19.7 nmol/g/min, while from 1-15 min we have measured the rate at 6.4 nmol/g/min. Using methionine sulfoximine as an inhibitor of the gamma-glutamyl cycle, the early rate was reduced to 10.0 nmol/g/min and the later rate to 3.7 nmol/g/min. These data are consistent with a two-compartment system regulating amino acid transport into the neurons. A mathematical model fit to these data indicates that the first compartment contains 8.3 nanomoles of tyrosine per gram brain or about 6.7% of the brain total. It is speculated that the first compartment consists primarily of the astrocytes.
Rates of tyrosine and lysine transport and incorporation into protein were measured in control and undernourished weanling rats. Undernutrition was induced by feeding lactating dams a low protein diet (12 percent casein) from birth to day 21. At weaning, body and brain weights of undernourished rats were 50 percent and 88 percent, respectively, of control values. Lysine and tyrosine transport rates into skeletal muscle were reduced by over 75 percent, more than twice the reduction seen in brain. Rates of amino acid incorporation into muscle protein were reduced by approximately 50 percent; the change in rate of incorporation into brain protein was not statistically significant. These data indicate that, in spite of marked retardation of amino acid transport into brain, the brain seems fully capable of maintaining normal rates of protein synthesis.
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Determinations were made of free amino acids in hemolymph collected from adult female Anopheles stephensi mosquitoes. The hemolymph first was fractionated by extraction and precipitation procedures, after which qualitative determinations of free amino acids were made by high voltage thin layer electrophoresis, and thin layer chromatography. Subsequent quantitative determinations were made with an automatic amino acid analyzer. The concentration of total free amino acids in the hemolymph rose 60--70% after the mosquito took a blood meal, and remained relatively constant thereafter. When mosquitoes took a blood meal infected with the rodent malaria parasite Plasmodium berghei, the rise in total free amino acids was only 15--25%. The chief differences that occurred with individual free amino acids was that infected mosquitoes had greater increases in arginine, greater decreases in valine and histidine, and a total loss of detectable methionine.
Determinations were made of carbohydrates in hemolymph collected from adult female mosquitoes (Anopheles stephensi). First the hemolymph was fractionated by extraction and precipitation procedures, after which qualitative and quantitative determinations of carbohydrates were made by thin layer chromatography. The most abundant sugars found in the hemolymph were glucose and trehalose, though maltose, glucuronic acid, and inositol could be found after the mosquitoes took blood meals. After the mosquitoes ingested a noninfected blood meal, their hemolymph sugar levels rose almost 4-fold. There was less of an increase following a blood meal infected with the rodent malaria parasite, Plasmodium berghei. Depletion of sugars in the hemolymph of infected mosquitoes may result from direct utilization of sugar by the malaria parasite developing within the mosquito.
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The structure of "membranous cytochrome oxidase" has been investigated by X-ray diffraction, optical polarization spectroscopy and EPR spectroscopy. These studies indicate that the cytochrome oxidase molecules are oriented symmetrically in the membrane profile with a significant portion of their mass occurring within the extravesicular surface of the membrane; the oxidase molecultes span the membrane profile; the distribution of the oxidase molecules over the plane of these membranes is non-crystalline; the oxidase molecules contain bundles of alpha-helical polypeptide chain segments where the average orientation of the helices is normal to the membrane plane; and the average heme orientation within the oxidase molecules is such that the normal to the heme plane lies in the plane of the membrane.