Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Prevalence of non-alcoholic steatohepatitis (NASH) among biopsied cases of a urban hospital in Japan: significance of measurement of serum ferritin in the detection of NASH]

From April 1989 to December 2004, we performed liver biopsy on 475 patients and obtained biopsy proven 35 cases of non-alcoholic fatty liver. Among them, 18 cases were diagnosed as non-alcoholic steatohepatitis (NASH). During the last three years, we have tried to detect NASH using ultrasonography and elevated value of serum ferritin (> 300 ng/ml). All of the eligible 7 cases biopsied during the course were diagnosed as NASH. In these 7 cases, ALT levels improved after the body weight loss accompanied by the parallel decrease of serum ferritin levels. Measurement of serum ferritin is useful in the detection of NASH but the normal value of ferritin cannot rule out the possibility of NASH.     

Progressive supranuclear palsy with asymmetric lesions in the thalamus and cerebellum,with special reference to the unilateral predominance of many torpedoes

This report concerns a notable case of progressive supranuclear palsy exhibiting asymmetric dentate nucleus and thalamic degeneration with numerous torpedoes. The neuronal loss in the ventral lateral nucleus of the thalamus was predominant on the right side, while in the cerebellum, a quantitative study revealed the contralateral predominance of the neuronal loss in the dentate nuclei and torpedo formation, with preserved Purkinje cells. The abnormal tau-protein-related profiles in the two nuclei did not show any laterality in their distribution, indicating that the dentatothalamic tract may have been affected in a non-specific way in this case. In addition, the fact that the prominent sites of torpedo formation and loss of dentate nucleus neurons are identical supports the hypothesis that the torpedoes may be formed in association with neuronal loss in the dentate nucleus because of a plausible metabolic change in Purkinje cells through synaptic detachment of their axon terminals. Received: 4 January 1996 / Revised: 27 March 1996 / Accepted: 5 April 1996     

Cell surface phenotype of in vitro proliferating lymphocytes in HTLV-I-associated myelopathy (HAM/TSP)

The in vitro proliferation of peripheral blood lymphocytes (PBLs) without any mitogenic stimulation is one of the hallmarks of human T lymphotropic virus type I (HTLV-I) infection. Recent evidence suggests a difference in the degree of the phenomenon between HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-I carriers (AC). In this article, we demonstrated several alterations in the features of the in vitro transformed lymphocytes between patients with HAM/TSP (n = 16) and AC (n = 8). The percentages of total CD8+ and CD8+CD28+ cells were significantly increased in the in vitro proliferating T lymphocytes derived from the patients with HAM/TSP when compared to those from AC. HAM/TSP was segregated from AC by the high degree of the proliferation of CD8+CD28+ cells. The expression of HTLV-I-specific antigens on the cultured PBLs was detected only in the subjects which showed low CD8+CD28+/CD4+ ratio of the in vitro proliferating lymphocytes. These findings suggest that this phenomenon distinguishes HAM/TSP from AC, not only in quantity but also in quality.     

Possible Role of Streptococcus Pyogenes in Mucocutaneous Lymph Node Syndrome. XII. Variable Responses of Platelets in MCLS Seem to Be Explainable by Streptococcal Pyrogenic Exotoxin

As a model system for mucocutaneous lymph node syndrome (MCLS), we have advocated and used mice which had been rendered tolerant to Streptococcus pyogenes-associated antigens by neonatal infection with group A fteta-hemolytic streptococci, because these mice have shown a variety of peculiar bioimmunological characteristics bearing a striking resemblance to those of MCLS patients. The results of our current investigations reaffirmed the reliability of the animal model by indicating that mice subjected to neonatal infection with 5. pyogenes , or inoculation with streptococcal pyrogenic exotoxin (SPE) in Freund's adjuvant, were perfect counterparts of patients with MCLS on account of their platelet activation and hyperaggregability in response to provocative treatment, which are familiar findings in this disease.     

Primary aortoduodenal fistula caused by duodenal tuberculosis without an abdominal aortic aneurysm: Report of a case

A 66-year-old man died of massive gastrointestinal hemorrhage caused by a fistula between the third portion of the duodenum and the abdominal aorta. An autopsy revealed that duodenal tuberculosis had resulted in the development of a fistula into the aorta with no pathological changes, and no active pulmonary tuberculosis was found. Duodenal tuberculosis and primary aortoduodenal fistula (ADF) without an aneurysm are both extremely rare. Thus, we report herein a unique case of primary aortoduodenal fistula without an abdominal aortic aneurysm, but associated with duodenal tuberculosis, and review the current literature.     

Inhibition of HIV-1 replication and syncytium formation by synthetic CD4 peptides

Summary Only one peptide of CD₄ (amino acid residues 70–132) among 16 synthetic peptide fragments selectively inhibited HIV-1 replication and HIV-1-induced syncytium formation. Several smaller peptides within this region did not show any activity, except for the peptide (86–132) which showed somewhat lower activity.     

A 62-year-old woman with early-onset Parkinson's disease associated with the PINKi gene deletion]

We report the first case of early-onset Parkinson's disease (EOP) with the PTEN-induced kinase 1 (PINK1) gene deletion in 62 years old Japanese female. The symptoms were started with unstable gait at the age 38. Parkinsonian symptoms became apparent in 45 years old. L-Dopa was markedly effective on her parkinsonian symptoms. However, equinovarus foot induced by L-Dopa intake appeared three months prior to the admission. On admission, she presented with mild cognitive impairment, severe depression, marked retropulsion, resting tremor in the left upper limb and mild hyperreflexia in the four limbs. Rigidity was not present. Mutational analysis revealed homozygous deletion from exon 6 to 8 in the PINK1 gene. An ethnic diversity in PINK1 mutation is suggested.