Autosomal recessive ocular albinism associated with a functionally significant tyrosinase gene polymorphism.

Autosomal recessive ocular albinism (AROA) is a disorder characterized by reduced pigmentation of the retina and iris, hypoplastic fovea, variably reduced visual acuity and nystagmus. Pigmentation of the skin and hair is normal, but is usually slightly lighter than in unaffected sibs. We analysed 12 unrelated patients with AROA, and found that two had abnormalities of the tyrosinase (TYR) gene. These two patients were each a compound heterozygote for a different pathologic mutant allele and an allele containing a 'normal' polymorphism, Arg402Gln, which results in a tyrosinase polypeptide with reduced thermal stability. In these patients, AROA thus appears to represent a clinically mild form of OCA1, with a fixed visual deficit resulting from low tyrosinase activity during fetal development but with normal pigmentation of the skin and hair postnatally.

Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.

Hermansky-Pudlak syndrome (HPS) is an often-fatal autosomal recessive disease in which albinism, bleeding, and lysosomal storage result from defects of diverse cytoplasmic organelles: melanosomes, platelet dense bodies, and lysosomes. HPS is the most common single-gene disorder in Puerto Rico, with an incidence of 1 in 1,800. We have identified the HPS gene by positional cloning, and found homozygous frameshifts in this gene in Puerto Rican, Swiss, Irish and Japanese HPS patients. The HPS polypeptide is a novel transmembrane protein that is likely to be a component of multiple cytoplasmic organelles and that is apparently crucial for their normal development and function. The different clinical phenotypes associated with the different HPS frameshifts we observed suggests that differentially truncated HPS polypeptides may have somewhat different consequences for subcellular function.

Gender difference in tooth autotransplantation with complete root formation: a retrospective survey.

Gender-related risk factors in the survival of transplanted teeth with complete root formation have not yet been identified. The purpose of this study was to investigate gender differences in tooth autotransplantation at dental clinics. We asked participating dentists to provide information on transplantations they had undertaken from 1 January 1990 to 1931 December 2010. The data were screened to exclude patients who underwent more than one transplantation, smokers or those whose smoking habits were unknown, patients under 30 or who were 70 years old and over, cases where the transplanted teeth had incomplete root formation or multiple roots and those with fewer than 20 present teeth post-operation. We analysed 73 teeth of 73 males (mean age, 47.2 years) and 106 teeth of 106 females (mean age, 45.3 years) in this study. The cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method. The cumulative survival rate for males was 88.3% at the 5-year mark, 64.8% at 10 years and 48.6% at 15 years; for females, it was 97.2% at the 5-year mark, 85.9% at 10 years and 85.9% at 15 years. A log-rank test indicated the difference between males and females to be significant (P = 0.011). There was also a significant difference in the main causes for the loss of transplanted teeth: males lost more transplanted teeth due to attachment loss than females (P < 0.05). These results indicate that males require more attention during the autotransplantation process, particularly at the stage of pre-operation evaluation and that of follow-up maintenance.

Influence of age on tooth autotransplantation with complete root formation.

The aim of this study was to investigate risk factors with age in the long-term prognosis of autotransplantation of teeth with complete root formation at dental clinics. Participating dentists were asked to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. The data were screened to exclude patients who were under 25 or 70 years of age and over, those who were smokers or whose smoking habits were unknown, those whose transplanted teeth had incomplete root formation or multiple roots and those with fewer than 25 present teeth post-operation. The participants in this study were 71 men (74 teeth) and 100 women (107 teeth) ranging from 25 to 69 years of age. Third molars were used as donor teeth in 89·0% of the cases. The participants were divided into three age groups of 25-39, 40-54 and 55-69. Survival analysis was conducted using the Kaplan-Meier method, and a log-rank test revealed that there were no significant differences in age groups for men or women. Cox regression analysis indicated that the survival of transplanted teeth was not influenced by age. However, although not statistically significant, the clinical success rate was lower in the 55-69-year-old group than that in the younger groups. These results indicate that if suitable donor teeth are available and the conditions are right, autotransplantation is a viable treatment for missing teeth regardless of the age of the patient.

A cross-sectional survey investigating the care of the primary dentition by general dental practitioners working in Japan and England.

OBJECTIVE: To compare treatment decisions about primary dentistry made by Japanese and English general dental practitioners (GDPs). METHOD: Four clinical scenarios were used to ascertain the clinical opinions of GDPs about what treatment to offer a 6-year-old boy with a carious molar. The first and second scenarios were a single distal and a distalocclusal cavity in a vital tooth without pain. The third was a large distal-occlusal cavity in a non-vital tooth without pain. The fourth was large distal-occlusal cavity in a non-vital tooth with pain. The participants were 234 GDPs in Japan and 322 GDPs in England. RESULTS: In the first scenario, 62.2% of Japanese GDPs preferred traditional restorative care compared with 34.7% of English GDPs. In the second scenario, Japanese participants were less likely to offer atraumatic treatment (16.5% vs. 34.9%). In the third scenario, Japanese dentists displayed a greater tendency to open the pulp chamber (55.2% vs. 7.6%). In the final scenario, 71% of Japanese GDPs would open the pulp chamber, whereas 50.3% of English GDPs favoured extraction. CONCLUSION: Japanese and English GDPs differed substantially in their views about the best treatment for a young child with a carious molar.

Novel method for endovascular fenestration using radiofrequency transseptal needle for aortic dissection with malperfusion syndrome.

Malperfusion syndrome is considered one of the most significant adverse events in aortic dissection disease and often requires invasive strategies to improve ischemia. We report the case of a patient who was presented with worsening claudication and leg rest pain due to malperfusion syndrome of type B aortic dissection. We successfully performed endovascular fenestration therapy to relieve the symptom by using a NRG radiofrequency transseptal needle (Baylis Medical, Montreal, Canada). We suggest that this novel method would be available for the patients with malperfusion syndrome of aortic dissection.

Organization and nucleotide sequence of the human Hermansky-Pudlak syndrome (HPS) gene.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, bleeding tendency, and lysosomal ceroid storage disease, associated with defects of multiple cytoplasmic organelles-melanosomes, platelet-dense granules, and lysosomes. HPS is frequently fatal and is the most common single-gene disorder in Puerto Rico. We previously characterized the human HPS cDNA and identified pathologic mutations in the gene in patients with HPS. The HPS protein is a novel apparent transmembrane polypeptide that seems to be crucial for normal organellar development. Here we describe the structural organization, nucleotide sequence, and polymorphisms of the human HPS gene. The gene consists of 20 exons spanning about 30.5 kb in chromosome segment 10q23.1-q23.3. One of the intervening sequences is a member of the novel, very rare class of so-called "AT-AC" introns, defined by highly atypical 5' and 3' splice site and branch site consensus sequences that provide novel targets for possible pathologic gene mutations. This information provides the basis for molecular analyses of patients with HPS and will greatly facilitate diagnosis and carrier detection of this severe disorder.

Cold-adaptation of human rotavirus.

A human rotavirus strain was cold-adapted for possible future use as a live vaccine. The original strain was isolated in 1980 in primary cynomolgus monkey kidney cells and has a serotype I and subgroup II antigenicity. The virus was serially passaged in African green monkey kidney cells; it was cultivated at 37 degrees C at the first stage of passages, and the cultivation temperature was then shifted down stepwise by 3 degrees C per each 10 passages. Finally the virus was passaged 10 times at 25 degrees C (total passage number of 55). The virus formed small-size plaques with irregular shaped borders at 31 degrees C. Growth at 25 degrees C of the cold-adapted virus was higher than that of the original virus. There was no difference between the migration patterns of 11 dsRNA segments in polyacrylamide gel electrophoresis of the original and the cold-adapted viruses.

Duplication of 15q11.2-q14, including the P gene, in a woman with generalized skin hyperpigmentation.

We describe a woman with 15q11.2-q14 duplication who had clinical manifestations of proximal 15q trisomy and hyperpigmentation. Within this region, the P gene, located at chromosome segment 15q11.2-q12, is associated with oculocutaneous albinism type II (OCA2) and with hypopigmentation in the Prader-Willi and Angelman chromosome 15q deletion syndromes. We therefore hypothesized that in this woman skin hyperpigmentation might result from a duplication of the P gene. We carried out chromosomal and interphase fluorescence in situ hybridization (I-FISH) analyses, and determined that the P gene is duplicated in this woman. Our findings demonstrate that trisomy of the P gene can be associated with skin hyperpigmentation.

The effect of attenuated vaccinia virus AS strain on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric cancer in rats.

The effect of vaccinia virus on MNNG-induced gastric cancer in rats was studied. Subcutaneous inoculation of the highly attenuated vaccinia virus AS strain at intervals of 3 days from the beginning of the experiment showed prominent antitumor activity not only against adenocarcinoma induced by MNNG in the glandular stomach but also against squamous cell carcinoma in the forestomach. Both UV-inactivated vaccinia virus and the DI strain of mammalian pathogenic vaccinia virus, from which the AS strain originated, showed no antitumor effect.

Occurrence of ganglioside GD3 in neoplastic astrocytes. An immunocytochemical study in humans.

GD3 immunocytochemical analysis was performed in 25 human specimens obtained by autopsy and biopsy from patients with astrocytomas, anaplastic astrocytomas, cerebellar astrocytomas and glioblastoma multiforme (GM), using the ABC method. Extraction of the ganglioside fraction from GM was used for thin-layer chromatography (TLC) analysis to confirm the specificity of anti-GD3 monoclonal antibody (DSG-1). Normal astrocytes were not immunoreactive for GD3. Neoplastic astrocytes of low- to high-grade tumours were GD3 immunoreactive. In GM, the multinucleated giant cells were also immunoreactive. All immunoreactivity present was within the cytoplasm. In TLC analysis, enzyme immunostaining of gangliosides from GM with DSG-1 showed only one positive band, which had the same TLC migration rate as GD3, indicating that GD3 of the ganglioside fraction from GM is the antigen detected by DSG-1. The presence of GD3 within the cytoplasm of neoplastic astrocytes showing invasive and proliferative properties, is of considerable interest. The implications and possible significance of the presence of GD3 in the cytoplasm in glioma cells are discussed.

Isolation of viruses from female Culex tritaeniorhynchus in Aedes albopictus cell cultures.

Isolation of viruses from female Culex tritaeniorhynchus was performed by inoculation of specimens into Aedes albopictus clone C6/36 cells as well as into suckling mouse brains (SMB). Altogether, 32,812 mosquitoes in 349 pools were processed from the specimens collected in Osaka Prefecture during the summer of 1978. Thirty-nine strains of Japanese encephalitis virus (JEV) were isolated in C6/36 cells in contrast to 27 strains in SMB. Twenty-four pools yielded JEV both in cell cultures and in SMB, 10 yielded JEV only in cell cultures, and three only in SMB. Two strains of Getah (GET) virus were isolated in cell cultures but not in SMB. Two of the 23 plaque isolates of a GET strain showed significantly lower titers of plaque formation on BHK21 cells or SMB-LD50, compared with the titer of plaque formation on C6/36 cells at 28 degree C. In addition, many unidentified filterable agents were detected by plaque formation on C6/36 cells.

Discharges of bulbar respiratory neurons during rhythmic straining evoked by activation of pelvic afferent fibers in dogs.

Each cycle of rhythmic straining evoked through the reflex center in the Kölliker-Fuse nucleus by stimulation of pelvic afferents in decerebrate dogs usually began in early expiration. During the rhythmic straining cycle, postinspiratory discharges of the phrenic nerve increased simultaneously with a burst of discharges of the nerves innervating the rectus abdominis and adductors of the glottis. While about half of the bulbar expiratory units discharged concurrently with the rhythmic straining, almost none of the inspiratory units examined did so. Nearly all expiratory bulbospinal units discharged concurrently, but none of the inspiratory bulbospinal units did so. These results show that expiratory neurons in the caudal bulb relay commands for rhythmic straining from the pontine reflex center to motor neurons of expiratory muscles, but that bulbar inspiratory neurons do not relay the commands to inspiratory motor neurons. Discharges concurrent with rhythmic straining were also evoked in all 4 postinspiratory units of the ventral group, 3 very early onset expiratory units and all 9 inspiratory-expiratory units of the dorsal group. Possible roles played by these respiratory neurons in the organization of rhythmic straining were discussed.