Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs) mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff) mice succumb to a profound neurodegenerative disease by 4-6 months of age. Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. We suggest that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.      

Modulation of large conductance calcium-activated K+ channel by membrane-delimited protein kinase and phosphatase activities

Large conductance Ca²⁺-activated K⁺ channel was identified and studied in excised inside-out membrane patches of freshly dispersed smooth muscle cells from rabbit gastric antrum. The current-voltage relationship of the single channel was linear from -80 to +80 mV of pipette voltage in which single channel conductance was 249±17.8 pS (n=19) in symmetrical concentration of K⁺ (145mM) across the patch. Activity of the channel (NPo) depended not only on cytoplasmic calcium concentration but also on membrane potential. MgATP increased NPo in a dose-dependent manner and Mg²⁺ was prerequisite for the effect. Okadaic acid (l00nM), inhibitor of protein phosphatases, increased NPo further in the presence of MgATP. Therefore, it would be concluded that activity of the calcium-activated K⁺ channel in gastric smooth muscle cells was controlled by phosphorylation state of the channel protein and the state is further modulated by membrane-delimited protein kinase and protein phosphatase activities.     

The nationwide epidemiological study of mental disorders in korea

The lifetime prevalences of DSM-III mental disorders using Korean version of DIS-III are presented. They were studied in 5,100 adults (aged 18 to 65) in household selected by two stage cluster sampling. Comparisons were made between regions, sex and age groups. International comparison with Epidemiologic Catchment Area program was also made.     

Anatomic bases for liver transplantation

Summary This study gathers the anatomic implications for a good liver transplantation. During hepatic removal a left hepatic a.exists in 20% of cases; a right hepatic artery originating from the superior mesenteric a. (SMA) can be the only arterial supply in 9% of cases; the whole lesser omentum has to be removed and the SMA from 6 cm to its origin. The SMA must be freed from the celiac ganglia and its ostium removed with the celiac trunk in an aortic patch cut on the anterior side in order to avoid the renal ostia. During total hepatectomy, dissection of the portal triad is often difficult because of portal hypertension dilating accessory portal veins (parabiliary arcade) and pedicular lymphatics. Nerve plexuses are thick in front of the hepatic artery or behind the portal triad. Transection of triangular ligaments leads to the retrohepatic inferior vena cava (IVC) that must be freed from its posterior tributaries (right suprarenal vein and inferior phrenic veins flowing either into the IVC or into the hepatic veins). One big problem during hepatic replacement is the biliary anastomosis which must be well irrigated. In the recipient, dissection up to the hilum preserves hepatic and pancreatico-duodenal pedicles. The biliary tract of the graft must be cut low, behind the pancreas, and several centimeters of the gastroduodenal artery must be preserved to save hepatic and gastroduodenal pedicles.

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Bases anatomiques de la transplantation hépatique

Résumé Ce travail rassemble les notions anatomiques nécessaires au bon déroulement d'une transplantation hépatique. Le prélèvement du greffon doit enlever tout le petit omentum contenant une éventuelle a. hépatique gauche née de l'a. gastrique gauche (20%) et emporter l'a. mésentérique supérieure jusqu'à 6 cm de son origine pour ne pas oublier une a. hépatique droite née de cette dernière: son ostium est pris avec le tronc clique dans un patch aortique découpé sur la face antérieure. Lors de l'hépatectomie totale, la dissection du pédicule hépatique est rendue délicate par l'hypertension portale qui dilate les veines portes diets accessoires (arcade parabiliaire) et les lymphatiques pédiculaires. Les plexus nerveux sont riches devant l'artère hépatique et derrière le pédicule. La section des ligaments triangulaires droit et gauche amène à la veine cave inférieure (VCI) rétro-hépatique qu'il faut libérer de ses afférences postérieures (en particulier la veine surrénale principale droite toujours haut située et les veines phréniques inférieures qui s'abouchent soit dans la VCI soit dans les veines hépatiques du carrefour). Lors du remplacement, l'anastomose biliaire doit être vascularisée. Chez le receveur la dissection jusqu'au hile permet de conserver les pédicules. La voie biliaire du greffon doit être coupée bas derrière le pancréas et les premiers centimètres de l'artère gastro-duodénale conservés pour préserver les pédicules hépatique et pancréaticoduodénal.

     

The role of Ureaplasma parvum serovar-3 or serovar-14 infection in female patients with chronic micturition urethral pain and recurrent microscopic hematuria

BackgroundUreaplasma parvum (UP) is commonly isolated in the genitor-urinary tract and may cause various clinical features, including microscopic hematuria (MH). Some UP serovars are more commonly related with specific urogenital disease, but the evidences have been conflicting. This study primarily aimed to research the possible associations between specific UP serotypes and genito-urinary pathogenicity in female patients showing MH with/without chronic micturition urethral pain (CMP).MethodsThis study retrospectively reviewed 276 female patients having MH with/without CMP, who visited health screening center or female infertility clinic. All patients underwent multiplex polymerase chain reaction (PCR) tests with vaginal and urine samples to evaluate the infection rate and serotypes of UP. The antimicrobial susceptibility of UP and the predictors of CMP among UP infected patients were also analyzed. All patients were followed up at least for 6-months.ResultsForty-nine patients (17.8%) showed urinary UP infection. Urinary UP serotyping showed the prevalence of seorvar-1, -3, -6 and -14 were 24.5%, 30.6%, 18.4% and 26.5%, respectively. 79.6% of the urinary UP positive patients accompanied vaginal UP infection. 22 patients of the cohort (8.0%) had CMP whereas serovars-3 and -14 accompanied CMP in 54.5% and 41.0% cases, respectively. No serovars-6 infection case had CMP. 26.4% of the cohort were infertile whereas 10.9% of these infertile patients were positive for urinary tract infection with UP serotype-3 or -14. Doxycycline, josamycin and pristinamycin were the most active antibiotics with the lowest rate of resistance (0.0%) for treating UP. At 1-month post-initial treatment with doxycycline, all UP serotypes were eradicated and no patient complained of urethral discomfort. However, simultaneous urinary and vaginal reinfection of serovar-3 (5 cases) and serovar-5 (1 case) were confirmed at 3-months post-initial doxycycline therapy. The logistic regression analyses revealed that serovars-3 [hazard ratio (HR) 1.354, P value 0.018] and -14 (HR 1.103, P value 0.046) were significantly associated with CMP in female patients having MH.ConclusionsUP serovars-3 and -14 infections could be associated with CMP in female patients having MH. Doxycycline, josamycin and pristinamycin were effective for treating UP. Serovar-3 showed higher reinfection rate than other serotypes after antibiotics treatment.     

Urolithiasis in renal and combined pancreas/renal transplant recipients

PURPOSE: Urological complications in renal transplant recipients will become more common with increasing numbers of transplantations as well as increased graft survival secondary to improvements in immunosuppression. Urinary stone disease may be one of those complications. We determine the current incidence of urinary stone disease in renal transplant patients based on contemporary immunosuppressive regimens. MATERIALS AND METHODS: We reviewed the records of 1,730 renal and 83 pancreas/renal transplantations performed during the cyclosporine era and identified 8 recipients (0.4%) with urinary stone disease, including 3 with renal pelvic stones, 1 with multiple ureteral stones and 4 with bladder calculi. RESULTS: Treatment ranged from conservative observation to open pyelolithotomy, and included percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy. The ureteral stones were removed with antegrade and retrograde ureteroscopy. The 4 bladder stones were treated with cystolithalopaxy. No case had significant permanent graft damage. Mean followup was 68.6 months. Mean serum creatinine was 1.5 mg./dl. (normal 0.5 to 1.3) at baseline and 2.38 after followup. CONCLUSIONS: While the incidence of upper tract urinary stone disease in renal (0.23%) and pancreas/renal (1.2%) transplant recipients is not statistically significant (p <0.45), the latter have significantly higher rates of bladder stones (4.8 versus 0%, p <0.001). The diagnosis of urinary stone disease in transplant recipients can be challenging because of the lack of symptoms but the treatment approach is the same as in the normal population.     

Pathogenesis and prevention of stomach cancer.

In many Western developed countries, the incidence of stomach cancer has declined dramatically. This decrease was an extraordinary, "unplanned triumph", especially when compared to other cancers. Stomach cancer is still the most prevalent malignant tumor in Korea. Most Koreans carry Helicobacter pylori in their stomach. Thus, a new hypothesis, based on the relationship between the host and Helicobacter pylori, is presented as the carcinogenesis of human stomach cancer. The reasons for why the N-nitrosamide hypothesis should be dismissed as the etiology of stomach cancer, and why the contemporarily available principles and practice of intervention strategies to rapidly decrease the surprisingly high prevalence rate of Helicobacter pylori infection are impractical at this moment, are explained. In order to introduce an alternative provisional strategy of the "planned triumph" for the population vulnerable to stomach cancer, vitamin C is defined as an anti-inflammatory agent on the basis of the pathogenesis of Helicobacter pylori infection.     

Genetic distances for the study of infectious disease epidemiology

Molecular epidemiologic studies of infectious pathogens 1) generate genetic patterns from a collection of microorganisms, 2) compare the degree of similarity among these patterns, and 3) infer from these similarities infectious disease transmission patterns. The authors propose a quantitative approach using genetic distances to study the degree of similarity between patterns. Benefits of such genetic distance calculations are illustrated by an analysis of standard DNA fingerprints of Mycobacterium tuberculosis in San Francisco collected during the period 1991-1997. Graphical representation of genetic distances can assist in determining if the disappearance of a specific pattern in a community is due to interruption of transmission or ongoing evolution of the microorganism's fingerprint. Genetic distances can also compensate for varying information content derived by DNA fingerprints of contrasting pattern complexity. To study demographic and clinical correlates of transmission, the authors calculated the smallest genetic distance from each patient sample to all other samples. With correlation of genetic distances and nearest genetic distances with previously understood notions of the epidemiology of M. tuberculosis in San Francisco, factors influencing transmission are investigated.