Prepro-thyrotropin releasing hormone 178-199 immunoreactivity is altered in the hypothalamus of the Wistar-Kyoto strain of rat.

The rat prepro-thyrotropin releasing hormone (TRH) 178-199 is derived from prepro-TRH by the actions of the endopeptidases, prohormone convertase 1 (PC1) and PC2. PPTRH 178-199 attenuates the synthesis and secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary both in vitro and in vivo, suggesting an inhibitory action on hypothalamic-pituitary-adrenal (HPA) axis function. This peptide also acts centrally to increase activity and decrease anxiety related behaviors. To elucidate the involvement of this peptide in these functions, we have compared the expression of PPTRH 178-199, PPTRH mRNA, and PC1 and PC2 mRNAs in the Wistar-Kyoto (WKY) and Wistar strains of rat. WKY rats have been shown to possess neuroendocrine abnormalities (HPA hyper-activity) and hyper-emotional behavioral characteristics. Immunohistochemical analysis of PPTRH 178-199 demonstrated significant strain differences in the paraventricular nucleus (PVN) of the hypothalamus and the parastrial nucleus (PSN). WKY rats had significantly greater numbers of immunoreactive (IR) cell body profiles (P<0.0005) than Wistar rats in the PVN and a significantly lower fiber density (P<0.002) in the PSN. Levels of PPTRH, PC1, and PC2 mRNA were not different between strains in any brain region examined. These data suggest that altered levels of PPTRH 178-199 in WKY rats could cause, at least in part, the hyper-activity of the HPA axis and the hyper-emotional behavioral characteristics seen in this rat strain. Such data fit with the hypothesis that PPTRH 178-199 is involved in the regulation of the HPA axis and behavior.     

Aerobic and non-aerobic forms of exercise in the treatment of anxiety disorders

We compared aerobic and non-aerobic forms of exercise in the treatment of anxiety disorders. Seventy-nine inpatients took part in the study. All met the DSM-III-R criteria for anxiety disorders, 71 per cent had the diagnosis panic disorder with agorphobia. Patients were randomly assigned to the two physical training conditions, aerobic and non-aerobic, by block randomization with respect to sex. Seventy patients completed the trial, and exercised for one hour three times a week for eight weeks. There was a significant increase in aerobic capacity in the aerobic group, but no change in the non-aerobic group. Both groups achieved similar and significant reductions in anxiety scores, but the differences between the groups were small and not statistically significant. There were four exercise-related dropouts in the aerobic group, none in the non-aerobic. All dropouts had the diagnosis panic disorder with agoraphobia. The study indicates that intensive aerobic exercise, with resulting increase in aerobic capacity, has no specific effect on the anxiety level in patients with anxiety disorders. The reductions in anxiety scores which in previous studies have been shown to be associated with physical fitness training are most probably mediated via psychological mechanisms, like distraction and mastering.     

Hypoxia induces p53 accumulation in the S-phase and accumulation of hypophosphorylated retinoblastoma protein in all cell cycle phases of human melanoma cells.

Hypoxia has been shown to induce accumulation of p53 and of hypophosphorylated retinoblastoma protein (pRb) in tumour cells. In this study, the cell cycle dependence of p53 accumulation and pRb hypophosphorylation in four human melanoma cell lines that are wild type for p53 was investigated using two-parameter flow cytometry measurements of p53 or pRb protein content and DNA content. The hypoxia-induced increase in p53 protein was higher in S-phase than in G1 and G2 phases in all cell lines. The accumulation of p53 in S-phase during hypoxia was not related to hypoxia-induced apoptosis or substantial cell cycle specific cell inactivation during the first 24 h of reoxygenation. pRb was hypophosphorylated in all cell cycle phases by hypoxia treatment. The results did not support a direct link between p53 and pRb during hypoxia because p53 was induced in a cell cycle-specific manner, whereas no cell cycle-dependent differences in pRb hypophosphorylation were detected. Only a fraction of the cell populations (0.60+/-0.10) showed hypophosphorylated pRb. Thus, pRb is probably not the only mediator of the hypoxia-induced cell cycle block seen in all cells and all cell cycle phases. Moreover, the cell cycle-dependent induction of p53 by hypoxia suggests that the primary function of p53 accumulation during hypoxia is other than to arrest the cells.     

Malocclusion associated with temporomandibular joint changes in young adults at autopsy

The purpose of this study was to identify variables of malocclusion that might be associated with previously reported temporomandibular joint morphologic findings. Before removing the left TMJ from each of 96 cadavers (age means equals 26.4 +/- 6.8 years), an intraoral examination was performed. Angle classification, crossbite, overbite, and overjet were evaluated. These parameters were analyzed with respect to their association with the following TMJ features: overall shape of the condyle and temporal bone, gross and histologic evidence of remodeling, and position of the articular disk. When combined with age, Angle Class II and III dentitions were associated with temporal and condylar deviation in form (DIF) (P less than 0.05) and more Class II dentitions were accompanied by histologic evidence of remodeling changes in the TMJs. Crossbite was associated with increasing presence of DIF in all components (P less than 0.01). Anterior crossbite was associated with DIF on the articular eminence (P less than 0.01). Deep overbite was more common in persons with flat condyles, open mandibular fossae, and anterior extension of the temporal articular surfaces (P less than 0.05). Abnormal overjet was more evident in those with DIF in the disk (P less than 0.05); greater overjet was associated with disk displacement (P less than 0.05). Considered together, abnormal overbite and overjet were associated with more extensive DIF on the condyle (P less than 0.05). In conclusion, malocclusion was associated with morphologic changes in the TMJ, particularly when combined with age. This evidence supports the belief that longer exposure to malocclusion may be associated with more extensive TMJ changes.     

Audiological rehabilitation of older people: visual and vibrotactile considerations

This paper discusses the peripheral and central visual and tactile pathways with respect to the diminishing integrity of the ageing nervous system. This discussion is based upon extant data derived from investigators in vision and vibrotactile sensation. The purpose in examining these investigations is to ascertain the problems associated with the use of vision and vibrotactile stimulation in the auditory rehabilitation of older people. Speed of processing and simultaneous use of pathways are factors to be considered carefully in order not to contribute to perceptual confusions. The writers hypothesize that the rehabilitative audiologist, when using the visual and tactile pathways of older patients for language processing is confronted with difficulties that are often encountered when using the auditory pathway in the presence of central auditory ageing effects. In view of the implications of the research findings in vision and vibrotactile sensation, suggestions are made to those professionals who work with older hearing-impaired people.     

Influence of tetracyclines on human polymorphonuclear leukocyte function

FIAC [1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine], FIAU [1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil], and FMAU [1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil] were evaluated for their efficacies in the treatment of genital infections with herpes simplex virus type 2 in guinea pigs. Intraperitoneal administration of these drugs in daily doses of 100 mg/kg of body weight initiated 24 h after virus inoculation and repeated 2 successive days thereafter inhibited development of genital lesions and reduced shedding of virus without evoking untoward reactions. In a comparative study with this 3-day dosage schedule, the efficacy of daily doses of 50 mg of FMAU per kg was greater than that of the same doses of FIAC and FIAU, in that order; all these were more effective than daily doses of 50, 100, or 200 mg of acyclovir or of 500 mg of phosphonoformic acid per kg. These differences in efficacy were enhanced when treatment was delayed for 2 to 3 days after inoculation.     

Effect of tetracyclines and UV light on oxygen consumption by human leukocytes.

When polymorphonuclear leukocytes were stimulated with zymosan, a sharp rise in oxygen consumption was observed. In the presence of doxycycline, we observed a further increase in oxygen consumption when the phagocytosing cells were exposed to UV light. When the light was turned off, oxygen consumption of the cells almost ceased, indicating photodamage to polymorphonuclear leukocytes during irradiation. Irradiation of the polymorphonuclear leukocytes for 20 min in the presence of doxycycline (10 micrograms/ml) before phagocytosis completely abolished the rise in oxygen consumption initiated by zymosan. Demethylchlortetracycline and light exposure also caused a marked reduction of polymorphonuclear leukocyte oxygen consumption, whereas oxytetracycline, lymecycline, chlortetracycline, and minocycline had only a slight or no photosensitizing effect. The photodamage induced by doxycycline and demethylchlortetracycline was inhibited by azide and enhanced in deuterium oxide. This was in accordance with singlet oxygen-mediated damage.     

Prognostic significance of computed tomography of the brain in thrombotic thrombocytopenic purpura

We studied the prognostic value of computed tomography (CT) of the brain for neurologic morbidity in patients with thrombotic thrombocytopenic purpura. On review of Mayo Clinic records for 1975 through 1985, we found 32 patients with thrombotic thrombocytopenic purpura, 20 of whom had undergone CT of the brain during their hospitalization. Despite major neurologic symptoms and signs, normal CT findings were associated with complete neurologic recovery. Seventy percent of patients with normal results of CT of the brain recovered and had no neurologic deficits, whereas 80% of patients with CT abnormalities died or had permanent neurologic sequelae. A review of the literature supports these conclusions. Thus, we suggest that CT of the brain be done in any patient with thrombotic thrombocytopenic purpura and neurologic deficits. Regardless of the severity of neurologic involvement, normal CT findings should encourage continued vigorous treatment of the patient because a normal scan supports the possibility of full clinical recovery.     

Hemopoietic colony growth-promoting activities in the plasma of bone marrow transplant recipients.

Plasma samples were obtained from 34 bone marrow transplant (BMT) recipients before and after administration of the preparative regimen and tested for their ability to promote and/or support growth of hemopoietic colonies. The ability of plasma samples to promote colony formation on their own was tested on normal nonadherent target cells without addition of exogenous growth factors. The growth-supporting activity was examined in the presence of medium conditioned by phytohemagglutinin-stimulated leukocytes (PHA-LCM) and/or erythropoietin (EPO). A series of kinetic changes was routinely observed. Pretransplant samples rarely gave rise to colonies without addition of exogenous growth factors. Plasma samples obtained after completion of the preparative regimen demonstrated increments of growth-promoting activities for megakaryocyte and granulocyte-macrophage progenitors (CFU-Meg and CFU-GM), respectively, that peaked between 7 and 21 d after transplantation. By day 30, activity levels of some patients had returned to pretransplant values, whereas in other patients, activities remained elevated. Persisting activity levels were associated with delayed engraftment. In contrast, activities for progenitors committed to erythropoiesis (BFU-E) and pluripotent precursors (CFU-GEMM) were only rarely observed. The activities were independent of febrile episodes. Their growth-promoting influence on CFU-GM could be neutralized completely by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies. These data suggest that at least some of the observed activities in post-BMT plasma are related to GM-CSF. The growth-supporting activities of pretransplant plasma samples are lower than normal plasma when tested on CFU-Meg and CFU-GM. The growth-supporting activities improved transiently within the first month after BMT. A decline during the second and third month was followed by a gradual return to activity levels that were comparable to normal plasma. The effects of these plasma samples on BFU-E and CFU-GEMM were assessed with PHA-LCM and EPO. Similar to CFU-Meg- and CFU-GM-supporting capabilities, they improved transiently after BMT with a return of normal support function after 5-6 mo. The observed endogenous production of growth-promoting and growth-supporting activities for hemopoietic progenitors may serve as a background to design clinical trials for the timely administration of recombinant hemopoietic growth factors to BMT recipients.