Systemic lupus erythematosus.

Systemic lupus erythematosus is a polysystemic disease with a high incidence of associated glomerulonephritis. Patients with sle rarely have the destructive arthritis so characteristic of rheumatoid arthritis. An unusual case is presented in which both glomerulonephritis and destructive arthritis occurred simultaneously, justifying the diagnosis of both systemic lupus erythematosus and rheumatoid arthritis.Immunohistochemical studies in lupus glomerulonephritis suggest that the pathogenetic mechanisms involve the deposition of immune complexes containing “nuclear” antigens and antinuclear antibodies in the lesions. The detection of mixed cryoglobulins in the sera of patients with sle suggests that a portion of the circulating immune complexes may precipitate at reduced temperatures and be detected as mixed cryoglobulins. The therapy of lupus glomerulonephritis with combinations of corticosteroids and azathioprine, though still in an investigative state, holds great promise. Similar abnormalities in diseases of minks and mice and in sle suggest similar pathogenetic mechanisms in the three species involved. Since the diseases in the lower animals have been associated with persistent viral infection, the investigation of the role of persistent infection in sle seems warranted.     

Microimplants of estradiol in the sexually dimorphic area of the hypothalamus activate ultrasonic vocal behavior in male Mongolian gerbils

The hormonal control of ultrasonic vocal behavior in the male Mongolian gerbil was examined by comparing the behavioral effects of androgen with those of estrogen administered to the preoptic-anterior hypothalamic area (POA-AH) in castrates. By measuring radioactivity released from solid "floating" POA-AH microimplants (mean diameter, 141 microns) of testosterone (3H-T, mean weight, 880 ng) in Experiment 1, we found that the steroid had a concentration gradient which fell rapidly from the edge of the microimplant, suggesting restricted diffusion. Using floating microimplants in Experiment 2, we studied the effects of testosterone propionate (TP, 650 ng), estradiol-17 beta benzoate (EB, 439 ng), or cholesterol (C, 478 ng) on rates of a frequency modulated ultrasonic vocalization emitted during sexual interactions. The effects on the upsweep call were compared with those on sexual mounting. The upsweep rate remained significantly below precastration levels in C implanted males. EB reinstated upsweep calling within 5 days, 3 days earlier than TP microimplants. Mounting in EB implanted males was maintained at precastration levels, whereas TP implantation restored mounting to precastration levels only after 5 days. EB was effective in inducing ultrasonic vocalizations when placed in, or near, the sexually dimorphic area (SDA) in the medial preoptic area (POM). Our results indicate that brain mechanisms underlying both ultrasonic vocalizations and mounting are directly sensitive to estradiol (E2) in the male gerbil. We conclude that E2 affects mechanisms in the SDA associated with ultrasonic calling and suggest that T is likely to act via aromatization products in the brain.     

Site-directed mutagenesis of GLUT1 in helix 7 residue 282 results in perturbation of exofacial ligand binding.

The structure-function relationship of the HepG2/erythrocyte-type glucose transporter (GLUT1) has been studied by in vitro site-directed mutagenesis. Chinese hamster ovary clones in which glucose transporters were transfected were shown by Western blotting with a GLUT1 anti-COOH-terminal peptide antibody to have expression levels of Gln282----Leu, Asn288----Ile, and Asn317----Ile mutations that were comparable with the wild type. All three mutant GLUT1 clones had high 2-deoxy-D-glucose transport activity compared with a nontransfected clone, suggesting that these residues are not absolutely required for the transport function. We have examined the possibility that the inner and outer portions of the transport pathway are structurally separate by measuring the interaction of the mutant transporters with the inside site-specific ligand cytochalasin B and the outside site-specific ligand 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 -yloxy)-2- propylamine (ATB-BMPA). All three mutant GLUT1 clones showed high levels of cytochalasin B labeling, and the N288I and N317I mutants showed high levels of ATB-BMPA labeling. In contrast to the transport and cytochalasin B labeling results, the transmembrane helix 7 Gln282----Leu mutant was labeled by ATB-BMPA to a level that was only 5% of the level observed in the wild type. We have confirmed that this mutant was defective in the outer site by comparing the inhibition of wild-type and mutant 2-deoxy-D-glucose transport by the outside site-specific ligand 4,6-O-ethylidene-D-glucose. 4,6-O-Ethylidene-D-glucose inhibited wild-type transport with a Ki of approximately 12 mM, but this was increased to greater than 120 mM in the Gln282----Leu mutant. Thus, of the 3 residues mutated in this study, only glutamine 282 substitution causes a major perturbation in function, and this is a specific and striking reduction in the affinity for the outside site-specific ligands ATB-BMPA and 4,6-O-ethylidene-D-glucose.     

Active fragments and analogs of the insect neuropeptide leucopyrokinin: structure-function studies

Evaluation of analogs of the blocked insect myotropic neuropeptide leucopyrokinin (LPK) has demonstrated its relative insensitivity to amino acid substitution in the N-terminal in contrast to the C-terminal region. Truncated analogs of LPK without the first, second, and third N-terminal amino acids retain a significant 144%, 59% and 30% of the activity of the parent octapeptide, respectively. The [2-8]LPK analog is the first fragment of an insect neuropeptide to exhibit greater activity than the parent hormone. In contrast, truncated analogs of the insect myotropic, proctolin, exhibit little or no activity. The pentapeptide fragment Phe-Thr-Pro-Arg-Leu-NH2 has been identified as the active core of LPK.     

Studies on the biochemical basis of the nutritional quality of tsetse fly diets

Batches of freeze-dried pig and cow blood, whose nutritional value to G. p. palpalis ranged from low to near optimum, were analysed for amino acid, triglyceride and cholesterol content. The results of the chemical analyses were compared with the nutritional quality parameters observed when each batch of blood was fed to G. p. palpalis in an attempt to establish a chemical basis for the nutritional quality of diets for Glossina. In general, those pig or cow blood diets that had a higher nutritional quality also had a significantly higher amino acid content than the suboptimal diets. There were significant differences between the triglyceride and cholesterol content of pig and cow blood, with pig blood having more triglyceride, but less cholesterol than bovine blood. There was no apparent correlation between the triglyceride and cholesterol content and the nutritional quality of blood.     

Does phospholipase C stimulate thymide kinase activity of rat liver extracts prepared after partial hepatectomy.

Our purpose was to determine whether phospholipase C stimulated thymidine kinase activity of regenerating rat liver. We determined effects of phospholipase C upon TMP formation by rat liver extracts prepared at 0, 12, 24, 36 and 48 hr following partial hepatectomy. Data were obtained which supported these conclusions: (a) Commercial preparations of phospholipase C contained nucleoside phosphotransferase activity; (b) phospholipase C exerted no appreciable stimulatory influence upon thymidine kinase activity of regenerating rat liver; and (c), apparent stimulation of thymidine kinase was associated with linked activities of two enzymes, viz., liver extract-ATPase activity and nucleoside phosphotransferase activity.     

Accuracy and precision of a wrist movement when vibrotactile prompts inform movement speed

Abstract

Purpose: This study investigated the effect of movement speed on task accuracy and precision when participants were provided temporally oriented vibrotactile prompts. Materials and methods: Participants recreated a simple wrist flexion/extension movement at fast and slow speeds based on target patterns conveyed via vibrating motors affixed to the forearm. Each participant was given five performance-blinded trials to complete the task at each speed. Movement accuracy (root mean square error) and precision (standard deviation) were calculated for each trial in both the spatial and temporal domains. Results: 28 participants completed the study. Results showed temporal accuracy and precision improved with movement speed (both: fast?>?slow, p?<?0.01), while all measures improved across trials (temporal accuracy and precision: trial 1?<?all other trials, p?<?0.05; spatial accuracy: trial 1 and 2?<?all other trials, p?<?0.05; spatial precision: trial 1?<?all other trials, p?<?0.05). Conclusions: Overall, temporal and spatial results indicate participants quickly recreated and maintained the desired pattern regardless of speed. Additionally, movement speed seems to influence movement accuracy and precision, particularly within the temporal domain. These results highlight the potential of vibrotactile prompts in rehabilitation paradigms aimed at motor re-education.