Discovery of the parkin gene; the gene for young onset autosomal recessive parkinsonism (AR)]

We discovered the gene for young onset autosomal recessive parkinsonism in 1998. We were gifted two lucky episodes. This is a short history on how we were able to discover the gene in a short period. We were primarily interested in the pathogenesis of sporadic Parkinson's disease (PD). We decided to do a genetic association study using a polymorphism of manganese superoxide dismutase (Mn SOD), as it is located at the pivotal position of oxidative stress and mitochondria. While we were screening many patients, we encountered what appeared to be young onset autosomal recessive family, which appeared to be linked to the sod2 locus, which had been mapped to the long arm of chromosome 6. We did linkage analysis on 13 similar families and obtained lod score above 9. Another fortune was that while doing linkage analysis, we encountered a patient who showed complete absence of one of the microsatellite markers that we were using in the linkage analysis. We thought that the marker was likely to be located within the disease gene. We started molecular cloning using this marker as the initial probe. Eventually we were able to clone a novel gene, which we named as parkin.     

Gyrate atrophy of the choroid and retina: 15 Japanese patients.

We examined 15 Japanese patients who had gyrate atrophy of the choroid and retina with hyperornithinaemia. Their visual acuities fell to 0.2 or worse in the second or third decade of life. Myopia developed late in the first decade, and the refractions decreased to -10 or -15 dioptres at age 20. Tunnel vision developed at approximately age 20. Our results suggested that the visual functions of Japanese patients were worse in the third decade or later than similarly affected Finnish patients.     

Non-dopaminergic projections from the substantia nigra pars lateralis to the inferior colliculus in the rat.

The substantia nigra pars lateralis (SNI) of the rat was found, by the anterograde and retrograde tracing methods, to send projection fibers to the peripheral shell region surrounding the central nucleus of the inferior colliculus (IC), bilaterally with a clear-cut ipsilateral dominance. SNI neurons sending their axons to the IC were distributed throughout the entire rostrocaudal extent of the SNI. None of these SNI neurons showed tyrosine hydroxylase-like immunoreactivity.     

One hundred and one cases of bronchoplasty for primary lung cancer

The results of 101 consecutive bronchoplasties performed between 1979 and 1993, including 8 cases of pneumonectomy, 88 cases of lobectomy, 3 cases of segmentectomy, and 2 cases of bronchial resection, are herein reported. Squamous cell carcinoma was the most common disease (59%) followed by adenocarcinoma (30%) and other diseases (11%). Anastomosis was satisfactory in 96 cases. Among the five stenosed cases, local recurrence was found in two cases, and there were three benign strictures. Two of the three benign strictures were treated with bouginage. The pulmonary artery was concomitantly reconstructed in seven cases with satisfactory results. Preoperative chemoradiotherapy was performed in 15 advanced cases and was followed by acceptable surgical results. The 5-year survival rate, according to the post-operative staging of the 86 patients without induction therapy, was 86% in stage I (19 patients), 49% in stage II (21 patients), and 27% in stage IIIA (40 patients). The overall survival rate was 46% at 5 years. There were two indications for this procedure i.e., a positive resection margin in 59 cases and positive hilar nodes in 42 cases. Better survival was noted in patients with squamous cell carcinoma, stage I, and surgery was thus selected for a positive resection margin, and not for a positive node.     

Impact of portal venous pressure on regeneration and graft damage after living-donor liver transplantation.

Several reports claim that portal hypertension after living-donor liver transplantation (LDLT) adversely affects graft function, but few have assessed the impact of portal venous pressure (PVP) on graft regeneration. We divided 32 adult LDLT recipients based on mean PVP during the 1st 3 days after LDLT into a group with a PVP > or = 20 mm of Hg (H Group; n = 17), and a group with a PVP < 20 mm of Hg (L Group; n = 15). Outcome in the H Group was poorer than in the L Group (58.8 vs. 92.9% at 1 year). Peak peripheral hepatocyte growth factor (HGF) during the 1st 2 weeks was higher in the H Group (L: 1,730 pg/mL, H: 3,696 pg/mL; P < .01), whereas peak portal vascular endothelial growth factor (VEGF) level during the 1st week was higher in the L Group (L: 433 pg/mL, H: 92 pg/mL; P < .05). Graft volume (GV) / standard liver volume (SLV) was higher in the H Group (L / H, at 2, 3, and 4 weeks, and at 3 months: 1.02 / 1.24, .916 / 1.16, .98 / 1.27, and .94 / 1.29, respectively; P < .05). Peak serum aspartate aminotransferase, bilirubin levels, and international normalized ratio after LDLT were significantly higher in the H Group, as was mean ascitic fluid volume. In conclusion, early postoperative PVP elevation to 20 mm of Hg or more was associated with rapid graft hypertrophy, higher peripheral blood HGF levels, and lower portal VEGF levels; and with a poor outcome, graft dysfunction with hyperbilirubinemia, coagulopathy, and severe ascites. Adequate liver regeneration requires an adequate increase in portal venous pressure and flow reflected by clearance of HGF and elevated VEGF levels.     

Protective efficacy of plasma-derived hepatitis beta vaccine in preventing perinatal transmission of HBV infection in infants of HBsAg/HBeAg positive mothers

Two hundred and four newborn infants of HBsAg/HBeAg carrier mothers were randomly assigned into three groups. Group A (69 infants) received full-dose HB vaccine, group B (70 infants) received half-dose HB vaccine at birth, 1 month, 3 months and group C (65 infants) were untreated control group. After twelve months follow-up the cumulative incidence of HBs antigenemia was 17.2%, 30% in group A, B respectively as compared with 78.4% in group C (p less than 0.001). The protective efficacy rates (PER) of group A and B were 78.1% and 61.7% respectively (p less than 0.05). The vaccine was also effective in preventing persistent HBsAg carriers (HBsAg positive for at least 6 months). The PER of group A and B were at least 74.9% and 49.2% respectively (p less than 0.001) at 1 year follow-up. From the practical point of view and economic reasons administration of full-dose HB vaccine give better protection to high risk infants.     

VALUE OF COMPUTED TOMOGRAPHY FOR EVALUATING THE INJECTION SITE IN ENDOSONOGRAPHY‐GUIDED CELIAC PLEXUS NEUROLYSIS

Endosonography‐guided celiac plexus neurolysis (EUS‐CPN) safely and effectively relieves pain associated with intra‐abdominal malignancies when the neurolytic is accurately injected. We applied contrast medium to evaluate the ethanol injection sites in patients who received EUS‐CPN due to abdominal pain caused by malignancies. We injected, under the guidance of endoscopic ultrasonography (EUS), ethanol containing 10% contrast medium into the celiac plexus of patients with intra‐abdominal pain due to malignancies. Immediately after the endoscopic therapy, patients underwent computed tomography (CT) to confirm the injection site. Images of distribution of injected solutions were classified into three groups. Injected solution dispersed in unilateral and bilateral anterocrural space was defined as ‘unilateral injection’ or ‘bilateral injection’, respectively. Injected solution located out of the anterocrural space was defined as ‘inappropriate injection’. Pre‐ and postprocedure pain was assessed using a standard analog scale. Before and 2, 4, 8, 12, and 16 weeks after the procedure, pain scores were evaluated. From April 2003 to May 2005, 13 patients were enrolled in this study. Improvement of pain score in the ‘bilateral injection’ and ‘unilateral injection’ groups was significantly superior to the change in the ‘inappropriate injection’ group. Although EUS‐CPN was effective in eight of 13 patients (61.5%), additional EUS‐CPN to the ‘inappropriate injection group’ increased the response rate to 84.6%. Injection of ethanol to the anterocrural space by EUS‐CPN produced adequate pain relief. Immediate examination by CT for confirmation of injection sites after EUS‐CPN would increase the likelihood of induction of pain relief.