Neuroprotective modulation of the unfolded protein response in Marinesco-Sj?gren syndrome: PERK signaling inhibition and beyond

<正>Individuals with Marinesco-Sj?gren syndrome(MSS;OMIM 248800),a genetic disease of infancy,suffer various disabilities,including loss of motor coordination due to cerebellar degeneration,and skeletal muscle weakness.After a progressive phase,symptoms stabilize and patients live to old age.Therefore,any pharmacological treatment that delays or attenuates cerebellar degeneration and/or muscle pathology can significantly improve their quality of life.We recently found that inhibiting the protein kinase RNA-like endoplasmic reticulum kinase     

Yersinia enterocolitica causing suppurative arthritis of the shoulder.

Yersinia enterocolitica is a rare cause of extra-intestinal disease. A case in a 60 year old butcher with hepatic cirrhosis who developed suppurative arthritis of the shoulder caused by Y enterocolitica is presented. There was no evidence of gastrointestinal infection or septicaemia. The severity of the illness was associated with various factors, including the underlying disease, the type of occupation, and the difficulties encountered in defining the optimal therapeutic regimen.     

Is colonic electrical activity a similar phenomena to small-bowel electrical activity?

PURPOSE: This study was designed to investigate colonic spike bursts regarding 1) their migration behavior, 2) their pressure correlates, and 3) comparing colonic short spike bursts with spike bursts from migrating myoelectric complex from the small bowel. METHODS: Rectosigmoid electromyography and manometry were recorded simultaneously in seven normal volunteers and electromyography alone in five others during two hours of fasting and for two hours after one 2,100-kJ meal. One patient with an ileostomy was also studied by the same method to record the migrating myoelectric complex from the terminal ileum during fasting. RESULTS: Three kinds of spike bursts were observed in the pelvic colon: rhythmic short spike bursts, migrating long spike bursts, and nonmigrating long spike bursts. The meal significantly increased the number of migrating and nonmigrating long spike bursts (from 25 to 38.7 percent of the recording time; P <0.01). These bursts of potentials showed a peak 15 minutes after the meal, which may be caused by the gastrocolic reflex. Migrating long spike bursts started anywhere along the rectosigmoid and migrated from there aborad 82 percent of the time and orad or in both directions in 10 or 7 percent of the time, respectively. They originated pressure waves 99 percent of the time. Short spike bursts were more frequent before the meal (15.1 percent before and 9.6 percent after the meal), but the difference was not significant; they neither propagated nor initiated pressure waves detected by the miniballoon. CONCLUSIONS: Migrating long spike bursts were the only potentials that migrated, sometimes for short distances. Short spike bursts are a different phenomenon from the small-bowel migrating myoelectric complex because they do not migrate; they can occur during the postprandial period and never originated intraluminal pressure waves.Supported by a grant from the Instituto Nacional de Investigação Científica, Proc. DBI-22086.Presented at the meeting of the Portuguese Congress of Gastrenterology, Vila Moura, Portugal, June 2 to 5, 1993.     

Unconjugated hyperbilirubinaemia in HBV carriers. Discriminant value of nicotinic acid (NA) test

Recently an unconjugated hyperbilirubinaemia, without any other abnormalities in liver function test, in 14.3% of HBV Japanese carriers has been noticed. Therefore, it would be possible to argue that the persistent infection of HBV in hepatocytes might play a role in an hypothetical metabolic derangement of bilirubin clearance. Twenty-five subjects in a group of 468 HBsAg+ patients (equal to 5.33%) presented an hyperbilirubinaemia. This percentage was not different from the 5.83% found in 3083 HBsAg- controls coming from the same institution. Therefore we could exclude that in our population the presence of HBV surface antigen itself would determine a statistically higher level of total bilirubin (TB) than in controls. The nicotinic acid (NA) loading test may reveal some bilirubin metabolic defects (i.e. Gilbert syndrome), even in subjects with normal basal values of TB. According to this background, we performed in 11 HBsAg+ males with basal TB higher than 17.1 mumol/l (1 mg%) (group A/1), 13 HBsAg+ males with basal TB lower or equal to 17.1 mumol/l (group A/2) and 14 HBsAg- normal controls matched for sex and age (group B) the NA test according to R?llinghoff et al. All the parameters calculated by the NA test resulted significantly different in the A/1 group compared with the B group, but not different from those found by several authors in the Gilbert's syndrome. On the contrary, no significant differences have been noticed between the latter group and the A/2 group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory impairment and metal exposure in a group of 68 industrial welders

A group of 68 currently employed welders were examined who were exposed to welding fumes either for the whole or for at least half the working day and who used at least two welding processes, which were mainly manual metal arc welding and metal active gas welding, but also metal and tungsten inert gas welding, or oxyacetylene welding. The welders were classified into 3 groups according to the class of materials used, i.e.: 1) only mild and stainless steel; 2) mild and stainless steel and other metals; 3) only other metals. Chronic bronchitis symptoms were observed in 22% of the subjects; signs of suspected radiological fibrosis were present in 18%, initial signs of radiological fibrosis in 4%. Small airway disease was prevalent in the smokers (28 smokers versus 2 nonsmokers); one worker had an obstructive syndrome and another a restrictive syndrome (both were smokers). There was a good correlation between years of exposure and: 1) MEF25 in non-smokers; 2) urinary cobalt in the whole group. There was also a correlation between smoking and FEV1, MEF50, MEF25, PaO2 and urinary cadmium. Serum copper was higher in workers exposed full time than in those exposed part time. Urinary chromium and cobalt and serum copper were high in steel welders, lower in welders using steel and other metals and low in welders using other metals. Urinary chromium was similar in smokers and non-smokers. Serum zinc was found to be of little use for biological monitoring of welders. Urinary chromium was studied for one week in 10 full-time exposed steel welders. The difference between the chromium values at the end of the workshift and those at the beginning was small (low current exposure); the chromium values at the end of the workshift were not uniform in the whole group (different past exposure levels).     

Neuquen,Argentina: Provincial Health Policies and Their Results*

ABSTRACT: A case study of the creation and implementation of a four-tier, integrated system of health care services in a sparsely populated, rural province in Argentina is described and discussed. Begun in 1970 in a diverse geographical area with a tradition of poor health status and inadequate health care resources, the provincial government set out to develop the human, physical and technological resources needed to provide a system of preventive and curative services appropriate to the health care needs of its residents. Innovative programs included training in management techniques, and epidemiological perspective of high risk, an emphasis on personnel development through a rural general medicine residency and an expanded nursing program as well as programs to attack infectious diseases, poor sanitation and dental problems were all developed in response to the distinctive features of the physical and social environment of the province. Improvements in traditional health indicators are reviewed and attributed to the program and administrative structures that were developed.     

Phenotypic and functional characteristics of tumor-associated lymphocytes in patients with malignant ascites receiving intraperitoneal infusions of recombinant interleukin-2 (rIL-2)

In the course of a phase I trial, in which recombinant IL-2 (rIL-2) was infused intraperitoneally (i.p.) in patients with peritoneal carcinomatosis, we evaluated the effect on "tumor-associated lymphocytes" (TAL) isolated from the ascitic fluid. No major changes in the percentages of cells expressing the CD3, CD4, CD8, Leu-7, OKM1 and WT-31 antigens were detected either in TAL or in peripheral blood lymphocytes (PBL) after 7 days of rIL-2 infusion. In contrast the percentages of TAL (but not PBL) expressing surface IL-2 receptor (Tac), or LAK-1 antigen were sharply increased. Analysis of cytolytic functions showed a potentiation of the lytic activity against natural-killer (NK) sensitive K562 target cells and the de novo appearance of lytic activity against fresh melanoma cells. In one patient IFN-gamma was detected in the ascitic fluid following rIL-2 infusion. T-cell clones derived from the patient were analyzed for the IFN-gamma production. While only approximately 40% of PB-derived control clones produced medium to low amounts of IFN-gamma, all of the TAL-derived clones produced medium to high amounts of the lymphokine.