Showing papers by "Rush University Medical Center published in 1973"

The Pharmacology of Tardive Dyskinesias

Abstract: The activity of dopamine at certain striatal dopamine receptors is related to the appearance of tardive dyskinesias in man. By analogy to Huntington's chorea and L-dopa-induced dyskinesias in parkinsonism, it appears that tardive dyskinesias are related to increased responsiveness of dopamine receptor sites as a result of neuroleptic-induced denervation hypersensitivity. It has been demonstrated that anticholinergic drugs worsen tardive dyskinesias in patients who have this disorder. It also appears that anticholinergic drugs decrease the threshold for tardive dyskinesias and thereby increase the incidence of this disorder. This implies that centrally active anticholinergic agents should not be used as a routine adjunct to neuroleptic therapy.

Studies on the Defective Haematopoietic Microenvironment of Sl/Sld Mice

Abstract: Summary. Femurs and spleens of both Sl/Sld and +/+ origin were implanted into both Sl/Sld and +/+ hosts. Eight weeks later the +/+ grafts incorporated more radioactive iron than did the Sl/Sld ones. The number of colony forming units (CFU) in the marrow of +/+ femur grafts and in +/+ spleen grafts was several fold greater than that in Sl/Sld grafts. X-irradiation of femur and spleen donors with 950 R reduced the number of CFU in the grafts to 40–60%, whereas grafts from donors exposed to 2500 R supported no CFU growth at all. The haematopoietic cells in the grafts after 6 weeks were almost entirely of host origin. These studies suggest that Sl/Sld mice have a congenital defect in some stromal elements of their haematopoietic tissues which are essential for the normal growth of CFU. These stromal factors are likely to be cellular, are less radiosensitive than are the CFU, and support the growth of CFU rather than actually differentiate into these cells. These stromal factors are present in both spleens and femurs of mice. The model described here appears to be a useful one for further characterizing stromal factors essential for supporting haematopoiesis.

Specific Neutralization of Human Hepatitis Type A in Marmoset Monkeys

Abstract: THE transmission of human hepatitis type A (infectious hepatitis) to marmoset monkeys, previously reported from this laboratory1–5, has been confirmed by several other laboratories6–9 but questioned by one10,11. To strengthen the case for considering the agents causing experimental hepatitis in marmosets as viruses of human hepatitis type A, and not as latent “marmoset hepatitis viruses” as has been suggested by the dissenting laboratory10,11, it was necessary both to show clearly the lack of induction of disease by normal human serum or plasma and to demonstrate specific neutralization by convalescent human serum of the hepatitis type A agents transmitted from man to marmosets. We describe such neutralization here.

Microchemical studies on acid glycosaminoglycans of the epiphyseal zones during endochondral calcification.

Abstract: The acid glycosaminoglycans of resting, columnar, hypertrophic and calcified zones of calf epiphyseal growth plate and of nasal septum cartilage were extracted with a dissociative solvent, 3M GuCl, according to Sajdera and Hascall (1969), to separate the glycosaminoglycans into an extractable pool and an unextractable pool which remains bound within the tissue. Epiphyseal cartilage required longer extraction times than did nasal septum cartilage to extract comparable amounts of acid glycosaminoglycans suggesting a stronger binding of proteoglycans within the tissue. Towards the calcification front the glycosaminoglycans were extracted more easily while in calcified zone not more than 30% could be extracted. Data obtained by the CPC microfractionation procedure of Antonopouloset al. (1964) indicated similar distribution according to molecular weight and/or charge density for extractable and unextractable chondroitin sulphate in nasal septum cartilage and in resting and columnar zones of epiphyseal growth plate. Unextractable glycosaminoglycans in hypertrophic and calcified zones were of predominantly low molecular weight and/or charge density compared to the extractable pool. Hyaluronic acid was unextractable in nasal septum and in resting, columnar and hypertrophic zones with increasing concentrations towards the calcification front. In calcified zone a shift to mainly extractable hyaluronic acid occurred. The significance of these findings is discussed.

Dopamine receptor site sensitivity in hyperthyroid guinea pigs: A possible model of hyperthyroid chorea

Abstract: Guinea pigs made hyperthyroid were found to have increased responsiveness to dopaminergic stimulation of the striatum as measured by the dosage of apomorphine necessary to elicit stereotyped behavior. A dosage of apomorphine which produced stereotyped behavior in only 3 out of 36 euthyroid guinea pigs induced this behavior in 18 out of 20 hyperthyroid guinea pigs. This observation suggests that striatal dopamine receptor site sensitivity is increased in hyperthyroidism and is consistent with the hypothesis that increased receptor site sensitivity plays a role in the pathophysiology of hyperthyroid chorea.

A Quinoline Methanol (WR 30090) for Treatment of Acute Malaria

Abstract: WR 30090 at a dose of 230 mg every 8 hr for 6 days has proven to be a safe, well-tolerated compound with photosensitivity proving to be a minor consideration. WR 30090 was found to be an effective medication for the treatment of acute malaria caused by several strains of Plasmodium falciparum. At the dose of 230 mg every 8 hr for 6 days, all of six men infected with a chloroquine-susceptible strain (Uganda I) were cured, all of 13 subjects infected with moderately chloroquine-resistant strains (Malayan Camp, Malayan Taylor, and Philippine Per) were cured, and 19 of 23 subjects infected with strains highly resistant to chloroquine (Vietnam Smith and Vietnam Crocker) were cured. All of five subjects infected with the chloroquine-resistant Vietnam Marks strain were cured with only 3 days of therapy. Blood-induced P. vivax (Chesson strain) infection showed a mixed response. Six out of seven volunteers were cured when treated for 3 days with WR 30090. The one recrudescence responded to a repeated course of therapy for 3 days. However, recrudescence occurred in one volunteer treated for 6 days. Treatment with WR 30090 failed to cure sporozoite-induced P. vivax (Chesson strain) infection in any of four subjects. In all subjects treated, there was good suppression of parasitemia and relief of symptoms. The susceptibility of the strains of malaria to WR 30090 to some degree parallels their susceptibility to chloroquine.

Disaggregation of Polyribosomes in Intact Gerbils Following Ischemia. An Ultrastructural Study

Abstract: Adult gerbils were subjected to either unilateral or bilateral common carotid artery ligation for varying periods of time with varying durations of recovery. Selected brain regions were prepared for ultrastructural study after perfusion fixation. Dissociation of polyribosomes was observed in neurons but not in glial cells of the cerebral cortex and thalamus after 30 minutes of unilateral occlusion with no recovery period. At the other extreme, disaggregation was present in all brain regions studied after 60 minutes of bilateral occlusion followed by a 60-minute recovery period. Still longer recovery periods result in the appearance of some neurons with normally aggregated polyribosomes. The results suggest that a relatively long period of ischemia induces a derangement of neuronal protein synthesis that may persist for some time after restoration of circulation.

Lingual-facial-buccal movements in the elderly. I. Pathophysiology and treatment.

Abstract: The syndrome of lingual-facial-buccal movements (dyskinesia) in the elderly involves the dopaminergic neuronal system and particularly the dopamine receptor sites of the corpus striatum. On the basis of experience with similar movements observed in other diseases and of the interpretation of animal studies on amphetamine-induced stereotyped behavior, agents that block dopamine receptor sites, e.g., chlorpromazine or haloperidol, are the treatment of choice for this syndrome. Anticholinergic drugs should not be used.

A Phenanthrene Methanol (WR 33063) for Treatment of Acute Malaria

Abstract: WR 33063, a phenanthrene methanol, was studied in human volunteers for tolerance and toxicity. In normal volunteers, it was possible to give 4.6 g in four divided doses without adverse effect for 10 days. At this dose level, there was neither evidence of photosensitivity nor adverse renal or cardiac effect. At a dose level of 1.6 g in four divided doses for 6 days, WR 33063 cured 18 of 23 nonimmune volunteers infected with the Smith strain of Plasmodium falciparum from Vietnam. In addition, infections due to the Marks and Braithwaite Vietnam strains were also treated because these strains represent a major therapeutic challenge to chloroquine; six of six and two of three volunteers, respectively, were cured. With the Malayan Camp strain, 1.6 g in four divided doses for 6 days cured all of five volunteers. The African Uganda I strain of chloroquine-responsive malaria was even more responsive to WR 33063; all of six men who received 1.6 g in four divided doses for 6 days were cured, and all of three men who received this same dosage for 3 days were cured. One subject infected with a Haitian strain of P. falciparum was treated and cured. Blood-induced infections with the Chesson strain of P. vivax also responded well to WR 33063 with four of five men cured. In all, 52 men received WR 33063 in tolerance trials, and 59 men with experimental malaria and one man with clinical malaria were treated with WR 33063.

Effects of hydroxyurea and radiation on hair matrix cells.

Abstract: Investigations were undertaken in CF1 mice to study the effects of hydroxyurea (HU) on hair matrix cell kinetics, and to assess the effects of combined administration of HU and irradiation on induction of temporary alopecia. HU 100 mg/kg was administered intraperitoneally and each animal received tritiated thymidine 0·5 μCi/g 30 min before biopsy. Serial biopsies were taken up to 48 hr after drug administration. Autoradiographs of anagen follicle squashes revealed sharp reductions in mitotic and labeling indices within 30 min. Depressed mitotic indices of 0·6–0·9% at 1–4 hr returned to normal (2·3%) after 6 hr, followed by cyclic mitotic ‘overshoot’, and were preceded by parallel changes in the labeling indices. HU-induced cellular damage was most marked 4 hr after HU injection, with almost complete recovery from injury observed at the 24 hr interval. The effects of varying the time intervals from 1 to 12 hr between HU administration and irradiation (650 rads) after injection of HU 1200 mg/kg were examined. Hair loss was measured 7 days later by photomicroscopy. Cyclic maximum alopecia was found at the 1–5 and 8–12 hr intervals, with relative ‘protection’ occurring at the 6–7 hr time periods.

Effect of pH on Metabolism and Ultrastructure of Guinea Pig Cerebral Cortex Slices

Abstract: Lactic acidosis is a prominent biochemical alteration which follows cerebral ischemia and is of sufficient degree to result in pH decrease in involved and adjacent tissue. Because of the significance of acidosis in the cerebral ischemic process, we have investigated ultrastruclural changes and some biochemical parameters under varying pH conditions using guinea pig cerebral cortex slices. Metabolic rates decreased markedly during acidic incubations, and increased only minimally during basic incubations. Acidic pH affected oxygen and glucose utilization rates and fine structure to a greater degree than did an equal change in pH from 7.4 toward the alkaline. Glucose consumption was affected by pH deviations from 7.4 to a greater degree than oxygen uptake.

Lingual‐Facial‐Buccal Movements in the Elderly. II. Pathogenesis and Relationship to Senile Chorea

Abstract: On the basis of clinical similarities, pathologic implications and the response to pharmacologic agents, it would seem that spontaneous lingual-facial-buccal dyskinesia of the elderly and senile chorea represent the early versus the final manifestations of the same degenerative process within the striatum.

Ultrastructural evidence against in vivo disaggregation of brain polyribosomes after administration of L-dopa or phenylalanine.

Abstract: L-dopa or phenylalanine was injected intraperitoneally into immature rats. Brain samples fixed and embedded by conventional methods were sectioned for electron microscopic study. In contrast to chemical evidence in the literature for disaggregation of brain polysomes in fractions of whole brain from animals so treated, we found no ultrastructural evidence of disaggregation in either neurons or glial cells. The fact that we and others have observed polysome disaggregation in electron micrographs of sections from other types of animal experiments suggests that our observation of stable polysomes in the present work is not the result of technical artifact, and that the disaggregation observed in brain fractions by others had probably not occurred in their intact animals. It is unlikely that the behavioral and physiological changes occurring in patients treated with L-dopa can be correlated with the state of aggregation of brain polyribosomes.

Isolation and characterization of a glycoprotein from human colostrum.

Abstract: A glycoprotein was isolated from the M-1 acid glycoprotein fraction of human colostrum. It had a molecular weight of 31200 and contained 27% galactose, 21.7% hexosamine, 8.0% fucose and 10.8% sialic acid by weight. The glycoprotein had no absorption maxima in the 240–300nm region, and was virtually free of ABH(O) and M and N blood-group activity. Alkaline borohydride cleavage of the glycoprotein resulted predominantly in the destruction of threonine and galactosamine.

Nachweis verschiedener antigener Determinanten vom interspecies Typ in RNS-Tumorviren (C-Typ) der Säuger / Evidence for the Existence of Different Antigenic Determinants of the Interspecies Type in Mammalian RNA-C -Type Tumor Viruses: Vergleichende serologische Untersuchung von Viren mehrerer Tierarten und von einem als Menschenvirus deklarierten Isolat / Comparative Serological Studies on Viruses of Various Animal Species Including a Virus Suggested to be of Human Origin

Abstract: In C-type particles of mammalian origin, two different antigenic determinants of the interspecies type have been revealed by a comparative study of murine-, feline-, suidian-, simian (woolly monkey) (SSV-1)-and RD114-viruses. With respect to the distribution of interspecies determinants, these viruses can be arranged into two distinct groups; one comprises the rodent- and cat-, the other the pig- and monkey-viruses. RD114-virus appears to share a certain non-interspecies antigenic component with cat viruses (strains Rickard and Gardner) but behaves, as far as its interspecies antigenic determinant is concerned, more similar to pig- and woolly monkey-viruses. In showing the serological differences mentioned, IgG antibody could replace whole serum.