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Biomedical subjects

R Hamada

Publications and source records attributed to R Hamada.

At least 19 recordsLinked to original sources

Isolated medial medullary infarction due to vertebral artery dissection.

A 54-year-old man developed left hemiparesis and tactile and deep sensory disturbance following onset of rightside cervical pain. These symptoms resulted from an isolated infarct in the right medial area of the upper medulla oblongata and intracranial vertebral artery (VA) dissection. Atherosclerotic disease of the VA is the most common cause of medial medullary infarction. In past reports of isolated medial medullary infarction, only a few cases involved VA dissection.

Angiography↗

Discovery of novel aldose reductase inhibitors using a protein structure-based approach: 3D-database search followed by design and synthesis.

Aldose reductase (AR) has been implicated in the etiology of diabetic complications. Due to the limited number of currently available drugs for the treatment of diabetic complications, we have carried out structure-based drug design and synthesis in an attempt to find new types of AR inhibitors. With the ADAM&EVE program, a three-dimensional database (ACD3D) was searched using the ligand binding site of the AR crystal structure. Out of 179 compounds selected through this search followed by visual inspection, 36 compounds were purchased and subjected to a biological assay. Ten compounds showed more than 40% inhibition of AR at a 15 microg/mL concentration. In a subsequent lead optimization, a series of analogues of the most active compound were synthesized based on the docking mode derived by ADAM&EVE. Many of these congeners exhibited higher activities compared to the mother compound. Indeed, the most potent, synthesized compound showed an approximately 20-fold increase in inhibitory activity (IC(50) = 0.21 vs 4.3 microM). Furthermore, a hydrophobic subsite was newly inferred, which would be useful for the design of inhibitors with improved affinity for AR.

Aldehyde Reductase↗

Detection of HBV RNA in peripheral blood mononuclear cells in patients with and without HBsAg by reverse transcription polymerase chain reaction.

We examined RNA of hepatitis B virus (HBV) in peripheral blood mononuclear cells (PBMCs) by the reverse transcription polymerase chain reaction (RT PCR) in 61 patients associated with HBV infection, in order to analyze the relationship between the transcriptional activity of HBV in PBMCs and the clinical characteristics. The presence of HBV RNA in PBMCs was detected in 19/51(37.1%) patients with HBsAg positive and in 1/10 (10.0%) patient with HBsAg negative patients. Six healthy controls were all negative. The frequency of HBV RNA positivity was detected in patients with high ALT level (P<0.05), serum HBeAg positivity (P<0.01) and serum HBV DNA level>/=0.7 Meq/ml (P<0.05). Moreover, HBV RNA in PBMCs was detected in one patient followed up for 2 years after HBsAg disappearance in serum, who had not HBV DNA but anti-HBc IgG, in serum. These results suggested that the transcription of HBV in PBMCs, was frequently detected in the patients with higher replication of the virus, but HBV RNA in PBMCs might be detected in a few patients who had no evidence of HBV replication serologically.

Journal Article↗

Deep white matter lesions on MRI, and not silent brain infarcts are related to headache and dizziness of non-specific cause in non-stroke Japanese subjects.

OBJECTIVE: Silent or asymptomatic cerebrovascular disease is believed to be an important risk factor for symptomatic stroke and vascular dementia. Although non-specific complaints such as mild to moderate headache and/or dizziness may also be caused by silent stroke, which remains a topic of controversy. METHODS: To investigate the relationship between silent brain infarcts and non-specific complaints, we assessed findings on magnetic resonance images using a common protocol in the following three groups of subjects; Group 1:78 subjects with non-specific complaints, Group 2:47 subjects with vascular risk factors, and Group 3:75 normal subjects without any subjective complaints or vascular risk factors. In addition to silent stroke, deep white matter lesions on MRI were also evaluated. All subjects were recruited from 12 institutes of the study group located at various parts of Japan. RESULTS: Silent brain infarcts were demonstrated in 44%, 43%, and 20% of subjects in Groups 1, 2, and 3, respectively. In Group 1, the average number of infarcts per individual who had silent brain infarction was 1.8, which was significantly fewer than 3.8 in Group 2 or 3.5 in Group 3 (p<0.0167). White matter lesions were found in 68%, 49%, and 11% in Groups 1, 2, and 3, respectively, indicating that non-specific complaints are more closely related to deep white matter lesions than to silent infarct lesions. Such white matter lesions were found more frequently in subjects with depressive state than in non-depressed subjects (67% vs. 39%, p=0.0155). CONCLUSION: The present results suggest that deep white matter lesions, rather than silent brain infarcts, appear to be important in producing headache and/or dizziness of non-specific cause and also to be related to the depressive state.

Aged↗

Prevalence and clinical characteristics of TT virus (TTV) in patients with sporadic acute hepatitis of unknown etiology.

BACKGROUND/AIMS: Recently, a novel DNA virus was isolated from the serum of a patient with post-transfusion non-A-G hepatitis and named TT virus. The aim of this study was to determine the prevalence and clinical characteristics of TT virus infection in patients with sporadic acute hepatitis of unknown etiology. METHODS: TT virus was investigated in the serum of 66 patients with sporadic acute hepatitis non-A-G and 50 healthy controls by semi-nested PCR with previously published primers. RESULTS: TT virus was detected in 17 (26%) of the 66 patients with sporadic acute hepatitis non-A-G and in a slightly higher rate (34%,17/50) in the control group. No significant differences in alanine aminotransferase or bilirubin concentrations were observed between the groups of patients with or without TT virus infection. Eighty per cent (12/15) of patients for whom follow up was possible had persistent viremia from 4 to 36 months, and 67% (8/12) of these patients had already normalized their levels of alanine aminotransferase. A phylogenetic tree constructed by the Neighbor Joining Method revealed that all isolates in this study were grouped within genotype 1a and 1b, without showing any association between genetic type and development of hepatic disease. CONCLUSIONS: Our results suggest that TT virus DNA is present not only in patients with sporadic acute hepatitis non-A-G but also in a large proportion of the general population. This virus was not likely to be the causative agent of hepatitis among the patients in this study.

Acute Disease↗

Long-term follow up of abdominal aortic aneurysm complicating Kawasaki disease: comparison of the effectiveness of different imaging methods.

A 2 month old boy with Kawasaki disease developed the rare complication of abdominal aortic aneurysm (AAA). He was followed up over 7 years by ultrasonography (2D-ECHO) with and without Doppler flow evaluation, angiography and computed tomography. Calcification was noted 33 months after the onset of the disease but the aneurysm did not decrease in size. 2D-ECHO was adequate for evaluating the size of an aneurysm, but did not show thrombus formation or calcification. Doppler flow studies did not show abnormally high blood flow velocities either at the inflow or outlet of aneurysms, which are indicative of stenosis. On the other hand an abdominal aortogram provided information regarding the luminal shape and abnormalities in flow pattern suggestive of thrombus formation. Fluoroscopy cannot demonstrate calcification in the early stages. Computed tomography (CT) was the imaging method of choice for the evaluation of obstructive or calcific changes; an organizing thrombus was clearly demonstrated and early detection of calcification was possible.

Aortic Aneurysm, Abdominal↗

Computed tomography in fetal methylmercury poisoning.

Cerebral computed tomography was studied in eight patients with fetal methylmercury poisoning. All patients had evidence of prenatal exposure to methylmercury and showed psychomotor retardation. All of them had abnormal computed tomography findings. The most common finding was sulcal and ventricular enlargement, with or without cisternal enlargement. These findings indicated generalized cortical and subcortical maldevelopment. The distribution of sulcal and fissural enlargement did not show specific dominance in central sulcus, calcarine fissure or cerebellum. This distribution contrasts with the location of focal atrophy present in adult methylmercury poisoning. The computed tomography findings were relatively mild compared with the clinical features and were not distinct from those in cerebral palsy.

Activities of Daily Living↗

Patients with homocystinuria: high metal concentrations in hair, blood and urine.

Patients with homocystinuria excrete a large amount of metal in their urine. Homocysteine similar to penicillamine, administration to methylmercury treated rats resulted in a large amount of urinary methylmercury excretion. These results suggested that the total metal amounts in the whole body of patients with homocystinuria might be decreased. However, actually metal concentrations in hair and plasma of these patients were higher than those of normal controls. High plasma and hair metal levels are not accounted for in patients with homocystinuria. The physiological metal excretory mechanism in which small amounts of metals bind to the small, plasma molecular substances filter through the kidney and emerge in the urine is necessary for reconfirmation. Strongly perturbed metal metabolism exists in the patients with homocystinuria.

Adult↗

Truncal hypesthesia in patients with Minamata disease.

Patients with Minamata disease (methylmercury intoxication) usually suffer from the glove and stocking type hypesthesia in the extremities. Recently it is believed that the sensory disturbance of the disease may be a manifestation of the cerebral involvement. The aim of this study was to determine the pain threshold of their extremities and body by algesimeter. The results showed that a majority of the patients had elevated pain thresholds in the body and the extremities, and suggest that the pain impairment is not responsible for the peripheral nerve involvement.

Aged↗

Neonatal tuberous sclerosis with heart and brain tumors.

A 6-day-old neonate with tuberous sclerosis having brain and cardiac tumors is reported. The patient presented with a seizure 20 minutes after birth. Cranial ultrasonography and computed tomography on admission showed a large and round high-density tumor lesion in the left frontal lobe. Echocardiography also showed a large tumor lesion beside the left ventricle wall, and a diagnosis of tuberous sclerosis was promptly made. Two months later, a periventricular calcified lesion was found on the demonstrated portion, and the tumor lesion initially observed in the brain had disappeared. These findings suggest that the initial tumor lesion found in the brain developed into a typical calcified lesion.

Brain Neoplasms↗

Post-traumatic stress disorder among Special Forces Vietnam veterans.

Fifty-seven Special Forces Vietnam Veterans were studied to determine if special selection and rigorous training affected the frequency and pattern of predictors of post-traumatic stress disorder (PTSD). No absolute immunity to PTSD was conferred. Frequency (25%) and predictors of PTSD were similar to those reported for other groups of Vietnam Veterans. Symptoms of PTSD were associated with poorer pre-service relationships, being wounded, being wounded after return from R&R, having friends missing in action, feeling guilt over the death of a friend, lack of emotional preparation to leave the unit or service, and failure to discuss feelings upon return from Vietnam.

Humans↗

Determination of urine thiocyanate in patients with amyotrophic lateral sclerosis.

It has been reported that amyotrophic lateral sclerosis-Parkinsonism-dementia in Guam might be related to the eating of Cycas seeds, which contain cyanide. Based on this assumption, we determined the urinary thiocyanate excretion level in patients with ALS and compared this with that of other neurological diseases. The assay method was designed to use column chromatography with Amberlite IRA 402. The thiocyanate level was determined using pyridine-barbiturate method. The 24-h thiocyanate level was higher in the ALS patients of the middle stages than in the normal control group (Wilcoxon's test, P less than 0.02). There were no significant differences between the ALS patient groups of the early and terminal stages, Kugelberg-Welander disease group, Duchenne type muscular dystrophy group and control group. From these results, we concluded that ALS patients were contaminated with cyanide or thiocyanate and that, along with rapid muscular atrophy, the thiocyanate excretion levels were high.

Adult↗