Catecholamine uptake, accumulation, and release in acute porphyria

Hypertension and tachycardia are well known features of acute porphyria and have been shown to be related to increased circulating catecholamines. The mechanism by which circulating catecholamines are increased was studied using the isolated perfused rat heart and human platelets as a model of adrenergic neuronal function. It was found that neither delta-aminolevulinate (ALA) nor porphobilinogen (PBG) blocked uptake or caused release in the isolated perfused rat heart. Platelets from six patients with acute prophyria, three in remission and three latent, with matching normal controls were studied with regard to their uptake of [(3)H]norepinephrine in the presence of ALA or PBG. It was found that ALA and PBG significantly reduced uptake and accumulation of [(3)H]-norepinephrine in patients with acute porphyria; however, no similar reduction in uptake and accumulation was observed in the platelets of normal controls. Therefore, it appears that there is a latent defect in the catecholamine uptake and (or) accumulation of platelets of patients with acute prophyria which only manifests itself in the presence of ALA or PBG. If platelet uptake serves as a model of adrenergic neuron uptake, this suggests that elevated circulating catecholamine levels during acute attacks of acute porphyria are caused at least partially by blockade of re-uptake into the sympathetic neurons.     

Response of the hypothalamic neurons to stimulation of the vestibular nerve and lateral vestibular nucleus in rabbits

Effects of single, double, and rhythmic stimulation upon hypothalamic neurons responding to the 1st excitatory phase of lateral vestibular nucleus stimulation, were studied. The data obtained show that activation of some hypothalamic neurons following stimulation of the lateral vestibular nucleus has a monosynaptic character. The findings suggest that ascending afferents from the lateral vestibular nucleus to the hypothalamus pass via oligo- as well as polysynaptic pathways.     

Regulation of Sos activity by intramolecular interactions

The guanine nucleotide exchange factor Sos mediates the coupling of receptor tyrosine kinases to Ras activation. To investigate the mechanisms that control Sos activity, we have analyzed the contribution of various domains to its catalytic activity. Using human Sos1 (hSos1) truncation mutants, we show that Sos proteins lacking either the amino or the carboxyl terminus domain, or both, display a guanine nucleotide exchange activity that is significantly higher compared with that of the full-length protein. These results demonstrate that both the amino and the carboxyl terminus domains of Sos are involved in the negative regulation of its catalytic activity. Furthermore, in vitro Ras binding experiments suggest that the amino and carboxyl terminus domains exert negative allosteric control on the interaction of the Sos catalytic domain with Ras. The guanine nucleotide exchange activity of hSos1 was not augmented by growth factor stimulation, indicating that Sos activity is constitutively maintained in a downregulated state. Deletion of both the amino and the carboxyl terminus domains was sufficient to activate the transforming potential of Sos. These findings suggest a novel negative regulatory role for the amino terminus domain of Sos and indicate a cooperation between the amino and the carboxyl terminus domains in the regulation of Sos activity.     

Nasopharyngeal colonization with nontypeable Haemophilus influenzae in chinchillas

Colonization of the nasopharynx by a middle ear pathogen is the first step in the development of otitis media in humans. The establishment of an animal model of nasopharyngeal colonization would therefore be of great utility in assessing the potential protective ability of candidate vaccine antigens (especially adhesins) against otitis media. A chinchilla nasopharyngeal colonization model for nontypeable Haemophilus influenzae (NTHI) was developed with antibiotic-resistant strains. This model does not require coinfection with a virus. There was no significant difference in the efficiency of NTHI colonization between adult (1- to 2-year-old) and young (2- to 3-month-old) animals. However, the incidence of middle ear infection following nasopharyngeal colonization was significantly higher in young animals (83 to 89%) than in adult chinchillas (10 to 30%). Chinchillas that had recovered either from a previous middle ear infection caused by NTHI or from an infection by intranasal inoculation with NTHI were completely protected against nasopharyngeal colonization with a homologous strain and were found to be the best positive controls in protection studies. Systemic immunization of chinchillas with inactivated whole-cell preparations significantly protected animals not only against homologous NTHI colonization but also partially against heterologous NTHI infection. In all protected animals, significant serum anti-P6 and anti-HMW antibody responses were observed. The outer membrane P6 and high-molecular-weight (HMW) proteins appear to be promising candidate vaccine antigens to prevent nasopharyngeal colonization and middle ear infection caused by NTHI.     

Expression of interleukin-6 in polymorphic reticulosis--immunohistochemical study of 5 cases

Peripheral T cell lymphoma encompasses lymphomas with a variety of histologic appearances and clinical patterns. Recently, it has been suggested that almost all of the histologic features described under the name of polymorphic reticulosis(PR), lethal midline granuloma, and midline malignant reticulosis can be included in those generally described for malignant lymphomas of peripheral T cell origin(PTCL). There have been few studies of pathogenesis or tissue damage mechanism in PR patients. The need for a precise mechanism for tissue damage has important therapeutic implications. Using immunohistochemical methods with polyclonal anti IL-6 antibody, the authors describe 5 cases of PR with clinically and pathologically typical PR demonstrating a high expression of IL-6. According to classification, 2 cases of grade 1 PR showed the highest expressions, and 2 cases of grade 2 PR with atypical lymphoid cells showed moderate activity, but one case progressed into frank lymphoma(grade 3) and lost IL-6 expression. This strongly implies that some cases of PR have a different mechanism of tissue damage from frank PTCL, despite the one disease spectrum. Further studies on more cases may help clarify the pathogenesis.     

Thoracoscopic T2-sympathetic block by clipping--a better and reversible operation for treatment of hyperhidrosis palmaris: experience with 326 cases

Although thoracoscopic sympathectomy or sympathicotomy is the best treatment for hyperhidrosis palmaris, a new approach of clipping only without transection of T2-sympathetic trunk is just as effective. Aside from the guaranteed cure of hyperhidrosis, this new method has fewer complications and has the advantage of recovery of the sympathetic tone in the hands if the procedure is reversed by the removal of the clips. Between March 18 and September 30 of 1996, 326 patients (190 female and 136 male with a mean age of 20.5 years) underwent thoracoscopic T2-sympathetic block by clipping to treat hyperhidrosis. Good results and few complications were noted during follow up six months to one year postoperatively. Five of the 326 patients, all female, had the operation reversed because of intolerable compensatory sweating. Three recovered from the compensatory sweating within two months and had less palmar sweating than before their sympathetic block; the fourth achieved relief of compensatory sweating after nine months, and the fifth reported no improvement.