Molecular and clinical characterization of glucokinase maturity-onset diabetes of the young (GCK-MODY) in Japanese patients.

AIMS: To investigate the molecular and clinical characteristics of the largest series of Japanese patients with glucokinase maturity-onset diabetes of the young (GCK-MODY), and to find any features specific to Asian people. METHODS: We enrolled 78 Japanese patients with GCK-MODY from 41 families (55 probands diagnosed at the age of 0-14 years and their 23 adult family members). Mutations were identified by direct sequencing or multiplex ligation-dependent probe amplification of all exons of the GCK gene. Detailed clinical and laboratory data were collected on the probands using questionnaires, which were sent to the treating physicians.　Data on current clinical status and HbA1c levels were also collected from adult patients. RESULTS: A total of 35 different mutations were identified, of which seven were novel. Fasting blood glucose and HbA1c levels of the probands were ≤9.3 mmol/l and ≤56 mmol/mol (7.3%), respectively, and there was considerable variation in their BMI percentiles (0.4-96.2). In total, 25% of the probands had elevated homeostatic assessment of insulin resistance values, and 58.3% of these had evidence of concomitant Type 2 diabetes in their family. The HbA1c levels for adults were slightly higher, up to 61 mmol/mol (7.8%). The incidence of microvascular complications was low. Out of these 78 people with GCK-MODY and 40 additional family members with hyperglycaemia whose genetic status was unknown, only one had diabetic nephropathy. CONCLUSIONS: The molecular and clinical features of GCK-MODY in Japanese people are similar to those of other ethnic populations; however, making a diagnosis of GCK-MODY was more challenging in patients with signs of insulin resistance.

Mitochondrial inclusion bodies (intracytoplasmic acidophilic droplets) in neurons of chicken spinal cords increase with age.

We studied the pathologic features of neurons that contain intracytoplasmic acidophilic droplets (IADs) in chicken spinal cords. The IADs were lustrous spheroid bodies scattered in the cytoplasm of neurons, variable in size, and protein-rich bodies stained eosinophilic with hematoxylin-eosin, acidophilic with Azan, blue indigo with phosphotungstic acid hematoxylin, and yellow-green with Elastica van Gieson stain histopathologically. Ultrastructurally, almost all IADs were observed as homogeneous highly electron-dense spheroid bodies enclosed by double-limited membranes. Small IADs were observed in mitochondria. Anatomically, IAD-CNs were observed only in the ventral horn of the spinal cord between the fourth sacral and third lumbal vertebrae, and they were particularly frequent in the third sacral vertebrae. Their appearance and accumulative amount were likely to increase with age, while the clinical and pathologic significances of IAD-CNs remain unclear.

Touch-Cure Polymerization at the Composite Cement-Dentin Interface.

Ceramic restorations are often adhesively luted onto the tooth prep. The so-called touch-cure concept was developed to yield optimum polymerization of composite cement at the restoration-cement-tooth interface for immediate bond stabilization. Although this touch cure is theorized to initiate polymerization at the interface when the accelerator in the primer makes contact with the cement, this process has not yet been proven. This study aimed to elucidate the mechanism of touch cure by measuring the degree of conversion (DC) of composite cement applied with or without an accelerator-containing tooth primer (TP) versus an accelerator-free primer using real-time Fourier-transform infrared spectroscopy (RT-FTIR) and attenuated total reflection (ATR)-FTIR. Interfacial bond strength was measured in shear mode, the accelerator composition confirmed by X-ray fluorescence analysis (XRF), and the interfacial interaction of TP and composite cement with dentin investigated by X-ray diffraction (XRD), focused-ion-beam scanning electron microscopy (FIB-SEM) with 3-dimensional interface reconstruction, and transmission electron microscopy (TEM). RT/ATR-FTIR revealed the significantly highest DC when the composite cement was applied with the accelerator-containing primer. XRF disclosed a vanadium compound as a novel chemical accelerator within TP, instead of a classic chemical curing initiator system, to set off touch cure as soon the cement contacts the previously applied primer. Although the TP contains the acidic functional monomer 10-MDP for adhesion to tooth tissue, touch cure using the accelerator-containing TP combined the fastest/highest DC with the highest bond strength. FIB-SEM and TEM confirmed the tight interfacial interaction at dentin with submicron hybridization along with stable 10-MDP also Ca-salt nanolayering.

Formaldehyde measurements in residential indoor air using a developed sensor element in the Kanto area of Japan.

UNLABELLED: We undertook this to determine the formaldehyde concentration in Japanese houses and the relationship between formaldehyde levels and the age and temperature of a house using a sensor element that we developed for time-integrated measurements of formaldehyde concentration in actual environments. We evaluated the correlation between the formaldehyde concentration estimated by the dinitrophenylhydrazine (DNPH)-derivatization method and that obtained with our sensor element. We found a linear relationship between the two results indicating that reliable measurements can be performed using the developed sensor element in actual environments. The indoor concentration of formaldehyde was determined in a study of 34 homes in the Kanto area of Japan, between September 28 and October 27, 2007. We obtained the highest formaldehyde concentrations of 92 ± 15 µg/m(3) for apartments 0-2 years after their renovation, and a simple linear relationship was found between formaldehyde concentration and the age of the apartment. We also found that the formaldehyde concentration in a room containing furniture increased by 10% when the temperature increased by 1°C. PRACTICAL IMPLICATIONS: This study contributed to the measurements of indoor formaldehyde levels. We have used a newly developed sensor for time-integrated measurements of formaldehyde concentrations. This sensor does not need a power supply during exposure to air, and does not need special skills to use. This research showed that homeowners successfully deployed the sensor at the desired place and desired period in their house by themselves. Formaldehyde is emitted by various off-gassing sources, such as furniture. Therefore, for example, homeowners may want to measure the change of formaldehyde levels in their house before and after installing new furniture. This sensor may also be deployed by occupants to reduce the cost of a large-scale exposure assessment study.

Certified reference material for radionuclides in fish flesh sample IAEA-414 (mixed fish from the Irish Sea and North Sea).

A certified reference material (CRM) for radionuclides in fish sample IAEA-414 (mixed fish from the Irish Sea and North Seas) is described and the results of the certification process are presented. Nine radionuclides (40K, 137Cs, 232Th, 234U, 235U, 238U, 238Pu, 239+240Pu and 241Am) were certified for this material. Information on massic activities with 95% confidence intervals is given for six other radionuclides (90Sr, 210Pb(210Po), 226Ra, 239Pu, 240Pu 241Pu). Less frequently reported radionuclides (99Tc, 129I, 228Th, 230Th and 237Np) and information on some activity and mass ratios are also included. The CRM can be used for quality assurance/quality control of the analysis of radionuclides in fish sample, for the development and validation of analytical methods and for training purposes. The material is available from IAEA, Vienna, in 100 g units.

Association of neonatal hyperbilirubinemia with bilirubin UDP-glucuronosyltransferase polymorphism.

OBJECTIVE: The incidence of nonphysiologic neonatal hyperbilirubinemia is twice as high in East Asians as in whites. We studied whether the condition was associated with mutations in the gene for bilirubin uridine 5'-diphosphate-glucuronosyltransferase (UGT1A1), a key enzyme of bilirubin catabolism. DESIGN: We analyzed the UGT1A1 gene in 25 Japanese neonates who had nonphysiologic hyperbilirubinemia (serum bilirubin >257 micromol/L) with no obvious cause. They had all received phototherapy. The background control population consisted of 50 Japanese neonates whose transcutaneous jaundice index was monitored during the first week of life. We detected mutations by direct sequencing of polymerase chain reaction-amplified fragments of the gene. RESULTS: We found a polymorphism for UGT1A1 in exon 1; a G-->A transition at nucleotide 211 caused arginine to replace glycine at position 71 of corresponding protein product (G71R). The frequency of the mutated allele in the hyperbilirubinemic group (0.34) was significantly higher (chi2 = 5.56) than in the control group (0.16). In the control group the peak transcutaneous jaundice index of the carriers of G71R was significantly higher than it was in the normal infants. CONCLUSIONS: The missense mutation causing G71R is the first reported polymorphism for UGT1A1, and the mutation is a risk factor for nonphysiologic neonatal hyperbilirubinemia. The high incidence of hyperbilirubinemia in the Japanese may be attributable to the high frequency of this missense mutation.

Progressive multifocal leucoencephalopathy with magnetic resonance imaging verification and therapeutic trials with interferon.

Progressive multifocal leucoencephalopathy was diagnosed by magnetic resonance imaging (MRI) and brain biopsy in a 44-year-old woman, for whom therapeutic trials with various antiviral agents were made. Despite early diagnosis and treatment, her neurological deterioration and extension of MRI-detectable lesions were not halted for a period of about 8 months. After the introduction of intrathecal beta-interferon therapy, her neurological status and MRI findings became stable and showed minimal improvement. Early diagnosis of this fatal disorder is important and intrathecal interferon therapy should be considered.

Possible role of plasminogen activator inhibitor 2 in the prevention of the metastasis of gastric cancer tissues.

The concentrations of urinary type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), and PAI-2 were measured in gastric cancer tissues and adjacent healthy mucosal tissues. Levels of u-PA, PAI-1 and PAI-2 were higher in cancer than in control tissues. PAI-1 levels were higher together with the progression of cancer however there were no differences in u-PA or PAI-2 levels. Tumors with higher PAI-1 and lower PAI-2 levels tend to metastasize to remote lymph nodes. When the numbers of involved lymph nodes were analyzed, tumors with the large number of metastatic lymph nodes showed higher PAI-1 and lower PAI-2 level. No difference was shown in u-PA levels among these groups. These tendencies were more significant in patients with progressed gastric cancer. These results suggest that tumor with higher PAI-2 levels tend to localize or have less tendency to metastasize to lymph nodes. On the other hand PAI-1 was generally higher in tumor with invasion into nearby tissue or with nodal metastasis.

Clinico-radiological findings of neuro-Behçet's syndrome.

We examined 21 cases of Neuro-Behçet's syndrome in detail, and present here their clinicoradiological characteristics. Clinically, signs of pyramidal tract and meningeal irritation were frequently observed. In contrast to previous reports, our study demonstrated a near equal frequency in the occurrence of focal cerebral lesions and that of focal brain stem lesions. Notably, our results showed that the atrophy of both the cerebrum and the brain stem was often observed, indicating the presence of continuous disease activity in the central nervous system (CNS). In accordance with the high frequency of meningeal irritation signs, all of our cases exhibited pleocytosis in the cerebrospinal fluid (CSF). These results indicated the possibility that chemical mediators secreted from infiltrating cells in the CSF may somehow inflict damage to the CNS in Neuro-Behçet's syndrome.

Multiple sclerosis in Hokkaido, the northernmost island of Japan: prospective analyses of clinical features.

We analyzed the clinical features of multiple sclerosis (MS) prospectively seen between July 1986 and October 1989 on Hokkaido island, the northernmost part of Japan. Clinical features were generally considered to be intermediate between the previous Japanese reports and those of Western countries. Devic's disease was rare and simultaneous bilateral visual loss at on set was not too common this series, differing from that previously reported of Japanese MS. The high incidence of acute transverse myelopathy and lesser involvement of the cerebellum, however, support the previous view. Further clinical and epidemiological studies will be necessary on this island.

Serum levels of circulating intercellular adhesion molecule 1 in hepatocellular carcinoma.

BACKGROUND/AIMS: This is a comparative study of the relationship between. MATERIAL AND METHODS: Serum levels of circulating intercellular adhesion molecule-1 (cICAM-1) were measured by ELISA assay in four patients with chronic hepatitis (CH), 16 with liver cirrhosis (LC), 38 with hepatocellular carcinoma (HCC), and in nine healthy controls. RESULTS: No significant difference in cICAM-1 levels was observed between LC and HCC. The cICAM-1 level in HCC did not correlate with tumor markers but correlated well with tumor size. cICAM-1 level in HCC Stage III + IV was significantly higher than that of Stage I, and was higher in HCC with liver metastasis as opposed to HCC without metastasis. Furthermore, the cICAM-1 level of HCC decreased significantly after hepatectomy. CONCLUSION: These findings showed a close relationship between cICAM-1 and the progress of intrahepatic metastasis of HCC, indicating a possibility for using cICAM-1 as a prognostic marker.

Influence of vitamin A on the quality of beef from the Tajima strain of Japanese Black cattle.

Influence of vitamin A on the beef quality of the Tajima strain of Japanese Black cattle was studied. Marbling scores were correlated with serum vitamin A concentrations just before slaughter (r = -0.38). The mean marbling score of the low vitamin A group that were not supplemented with vitamin A after 15 months of age was significantly higher than that of the group supplemented with high vitamin A. However, there was no significant difference in the marbling scores between the group that were not given vitamin A after 23 months of age and the high vitamin A supplemented group. These results suggest that vitamin A supplementation affects carcass marbling only if given before 23 months of age, in these cattle.

[A family of paramyotonia congenita].

We reported a family with paramyotonia congenita which affected six members through three generations. The homogenous clinical features presenting paramyotonia followed by flaccid tetraparesis were found in all patients. In gene analysis using patient's blood, previously identified sodium channel gene point mutations were not present, suggesting the possibility of another sodium channel gene mutation in this family.

[A case of granulomatous angiitis of the central nervous system presented with subacute mental deterioration resembling diffuse white matter disease].

We reported a 60-year-old man with granulomatous angiitis of the central nervous system (GACNS) manifesting as subacute mental deterioration. His first symptoms were nausea and vomiting which brought him to a hospital, where no abnormality was found except for gastritis. One month later, he began to feel dizziness and brain tumor was suspected by a neurosurgeon with the MRI findings such as abnormal T2 signal and swelling in his brainstem. While he was followed up, he gradually presented mental change, disorientation and dysmnesia with the abnormal T2 signal spreading over the cerebral white matter bilaterally. Corticosteroid therapy was started based on the suspicion of a lymphoproliferative disease, and his symptoms and the abnormal MRI findings improved. Then he was referred to our department for further evaluation. Because we could not find any evidence of systemic diseases and he had been almost fully recovered, we discontinued the therapy. Soon after that, his mental deterioration as well as the abnormal T2 signal lesions on MRI relapsed. By open brain biopsy, the diagnosis of GACNS was established, and steroid pulse therapy was started. His symptoms and the abnormal T2 signal lesions improved gradually and the steroid was tapered to the maintenance dose without remission. Since the laboratory and imaging findings are not specific for the diagnosis of the angiitis confined to the central nervous system, brain biopsy is recommended for these disorders.

[An autopsy case of Shy-Drager syndrome preceded by a urinary disturbance for over 20 years].

An autopsy case of Shy-Drager syndrome preceded by urinary disturbance for over 20 years was reported. A 43-year-old woman was admitted to our hospital because of urinary disturbance and orthostatic hypotension. At the age of 19 she developed urinary disturbance with polyuria and retention. These symptoms were getting worse with years, and at the age of 33 she was diagnosed to have neurogenic bladder of uninhibited type. During her hospital course her symptom became worse, and by the age of 42 she showed marked dysarthria, disturbance of smooth pursuit eye movement, Horner's syndrome, marked rigidity and tremor of four extremities, generalized hyperreflexia, marked limb and truncal ataxia, neurogenic bladder and orthostatic hypotension. Serial brain CT scan revealed progressive brain stem and cerebellar atrophy with clinical course. Severe autonomic nervous system dysfunctions were also documented. She died of respiratory failure at the age of 43. On autopsy, brain stem and cerebellum showed marked atrophy macroscopically. Microscopically marked depletion of neuron was seen in the substantia nigra, pontine nuclei, inferior olive, Purkinje cells, the intermediolateral column of spinal cord and Onuf's nucleus of S2. Although numerous cases of Shy-Drager syndrome have been reported in the past, there is no case which developed this syndrome after urinary disturbance of over 20 year's duration. We should be alert to observe the cases with longstanding urinary disturbances in order to not overlook degenerative disorders as exemplified in this case.

[A case of refractory pulmonary fistula, managed with bronchoscopic therapy using occluding spiral embolus].

We report a successful case of bronchoscopic therapy using occluding spiral embolus and fibrin glue for refractory pulmonary fistula. A 22-year-old female underwent left lower lobectomy for giant bulla of the lung. Air leakage began 6 days after lobectomy. Closing alveolar fistula was performed 12 days after first operation. Relapsing air leakage began 4 days after second operation. Bronchography revealed a fistula from left B1+2c. The insertion of embolus through bronchofiberscope, following administration of fibrin glue, was performed to close the fistula. This method is effective for refractory pulmonary fistula.

[Postoperative abdominal lymph node recurrence of intrathoracic esophageal cancer with a long-term complete response to radiation and split CF therapy (CDDP and 5-FU)--a case report].

We experienced complete remission in a patient with postoperative abdominal lymph node recurrence of intrathoracic esophageal cancer after treatment with radiation (60Co: 30 Gy) and split CF therapy (CDDP: 20 mg/day + 5-FU: 1 g/day for 5 days). Since then, this patient has remained in complete remission for 43 months with intermittent split CF therapy one or two times a year.

[The expression of neural cell adhesion molecule (NCAM), neural invasion and recurrence patterns in rectal cancer--a study using anti-NACM (neural cell adhesion molecule) antibody].

Neural invasion may be one of the main causes of local recurrence, but its mechanism has not been sufficiently clarified. We previously reported that the expression of NCAM on cancer cells was correlated with neural invasion in pancreatic cancer. In this study, we examined the neural affinity of rectal cancer cells and the relationship between neural invasion and recurrence patterns of rectal cancers. A total of 64 rectal adenocarcinoma were examined. Specimens from 17 patients (27%) revealed perineural invasion. The incidence of neural invasion increased with the frequency of venous invasion and the degree of lymph node metastasis, but not significantly. The incidence of the expression of NCAM in rectal cancer cell was 45.3 percent. Neural invasion of rectal carcinoma was significantly related to the expression of NCAM (p < 0.05). NCAM immunocytolocalization was classified into the focal type, and the diffuse type. Concerning the recurrence type, 8 of 9 cases that developed local recurrence showed either presence of neural invasion or expression of NCAM. Liver metastasis was associated with absence of neural invasion or NCAM expression. The expression of NCAM may contribute to local recurrence, whereas the absence of NCAM may predict liver metastasis.

[Interferon production and natural killer activity of peripheral blood lymphocytes obtained from patients with multiple sclerosis].

Interferon (IFN) -system of patients with multiple sclerosis (MS) during the stable stage of the disease activity was investigated. Thirty six patients were divided into 3 groups of mild, moderate and severe patients according to the scores of disability status scale (DSS). IFN-alpha producibility and natural killer (NK) activity of peripheral blood lymphocytes (PBL) or large granular lymphocytes (LGL) fractionated from PBL were determined by culturing with HeLa cells persistently infected with measles virus (HeLa/MV) and K562 cells. IFN-gamma was induced in PBL obtained from the patients using killed cells of Propionibacterium acnes (P. acnes), Listeria monocytogenes (LM) and Streptococcus salivarius (Str. sal.) and a lectin of concanavalin A (Con A). Both IFN-alpha producibility and NK activity of PBL obtained from the patients were depressed in parallel with the severity of DSS of the patients. The depressed NK activity of the patients could be recovered by neither IFN-alpha nor interleukin-2 added exogenously. In addition, the induction of IFN-gamma was also depressed in the patients in response to P. acnes and LM, but not Str. sal. or Con A. These results suggest that the defect of IFN-system observed in PBL of the patients may result from the depressed function of both LGL and T lymphocyte subpopulations which are responsive to P. acnes and LM. It is postulated that these immunocompetent cells might migrate to subclinical demyelinating lesions of central nervous system where cytokines including IFN-gamma were produced locally, and that their migration might result in the quantitative decrease of lymphocytes participating in IFN-system in PBL of patients with MS.