Masaru Kuriyama

Susceptibility of Helicobacter pylori isolates to metronidazole, clarithromycin and amoxycillin in vitro and in clinical treatment in Japan

Primary and acquired resistance to antibiotics is an important factor in determining the reason for treatment failure in Helicobacter pylori infection. We examined the relationship between the susceptibility of H. pylori isolates and the efficacy of chemotherapy.

Familial spastic paraplegia with mental impairment and thin corpus callosum

We described four patients in two families of unique familial spastic paraplegia (FSP) which was thought to be possibly autosomal recessive inheritance. All four patients had quite similar manifestations. Gait disturbance started at their second decade, then spastic paraparesis and mental deterioration progressed slowly. Cerebellar ataxia and sensory loss in the distal parts of four extremities were also slightly presented. In all patients, cranial MRI revealed marked thin corpus callosum with mild changes in the region of periventricular white matter and in the gray matter. Biopsied sural nerves of all patients showed chronic axonal degeneration with mild decrease of both large and small myelinated fibers. Electron microscopic study demonstrated crystalline-like inclusion bodies in the cytoplasm of Schwann cells in all patients. Despite extensive investigation for metabolic disorder, we could not find any abnormality. However an etiology have not established at the time presented, the combination of these clinical features suggested that the disorder could represent a specific clinical entity.

An autopsy case of mitochondrial encephalomyopathy: biochemical and electron microscopic studies of the brain

A 29-year-old single woman had recurrent stroke-like episodes. She developed loss of consciousness, myoclonic seizures, and lactic acidosis. She died at the age of 30. A muscle biopsy study revealed mitochondrial myopathy, and the postmortem biochemical analysis demonstrated decreased cytochrome c oxidase activity in the skeletal muscles by 20% of normal control. The brain had multiple ischemic lesions in the cerebral cortex without major vascular occlusions. We present this case as an autopsy case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with a partial deficiency of cytochrome c oxidase. The analytical electron microscopic study of the calcified small vessels in the globus pallidus revealed increased calcium, phosphorus and iron. No accumulation of chromium, nickel or zinc was noted in this case, which was different from the previously reported cases of basal ganglia calcification.

Low Levels of Serum Apolipoprotein AI and AII in Senile Dementia

Abstract: We studied the serum lipoprotein and apolipoprotein profiles in 44 patients with sporadic late‐onset Alzheimers dementia and 43 patients with vascular dementia. The levels of high‐density lipoprotein (HDL) cholesterol were lower in both patient groups than in a control group. Apolipoprotein A I and A II levels have decreased in both the patient groups, especially in the vascular dementia group. The HDL‐cholesterol levels correlated positively with the level of apolipoprotein A I, but not with the level of apolipoprotein A II. The ratios of apolipoprotein A I/A II have increased in both the patient groups. The apolipoprotein A II levels have disproportionally decreased in the patient groups. The serum apolipoprotein A II may involve the pathological process in the patients with senile dementia.

Experimental simvastatin-induced myopathy in rabbits

We induced experimental myopathy in rabbits by giving simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. After oral administration of simvastatin (50 mg/kg/day) for 2 weeks, serum CK was elevated in 5 of 7 rabbits; degenerating or necrotic fibers were seen in 3 rabbits. Using electromyography, myotonic discharges were found in the 2 rabbits examined. The combination of myotonic discharges, necrosis and raised serum CK levels suggests that the myopathy was induced by lesions of the muscle surface membrane.

Cerebrotendinous xanthomatosis : cranial CT and MRI studies in eight patients

SummaryWe report the findings on cranial computed tomography (CT) and magnetic resonance imaging (MRI) and their correlation with the clinical manifestations, disease severity and biochemical abnormalities in eight patients with cerebrotendinous xanthomatosis. CT revealed cerebral atrophy in seven cases, cerebellar atrophy in four and focal low density lesions in the cerebral white matter in two. T2-weighted MRI showed high signal lesions in the cerebral white matter, focal in four cases and diffuse in one, and in the globus pallidus in three patients, two of whom also had lesions in the cerebellar white matter. While severely affected patients showed variable CT and MRI abnormalities, our cases did not show the dramatic findings expected from the neurological manifestations. Diffuse lesions in the cerebral and cerebellar white matter have been emphasized in previous reports, but in our study the focal lesions in the cerebral white matter were also present; the globus pallidus was frequently involved.

Germanium myopathy: clinical and experimental pathological studies

SummaryPathological examinations were carried out on the skeletal muscle of a patient with germanium intoxication. The prominent histochemical finding was vacuolar myopathy with lipid excess, increased acid phosphatase activity and decreased cytochrome c oxidase activity. Ultrastructural lesions revealed a mitochondrial abnormality, autophagic vacuoles and accumulation of high electron-dense materials in deformed mitochondria and at the periphery of lipid droplets. Furthermore, the toxic effect of germanium on skeletal muscle was confirmed by the experimentally induced germanium myopathy, which showed autophagic degeneration, decreased cytochrome c oxidase activity and a mitochondrial abnormality with high electron-dense materials.

Nasu-Hakola disease (membranous lipodystrophy): clinical, histopathological and biochemical studies of three cases

We report 3 cases of Nasu-Hakola disease found in 2 families. These cases had identical clinical features with progressive spastic paraplegia and severe dementia after adolescence. They had no history of any skeletal symptoms, but roentgenographs of their bones presented characteristic evidence of polycystic osteodysplasia. All cases revealed not only manifestations of this condition in the central nervous system, but also peripheral neuropathy with axonal degeneration. The membranous structures in the adipose tissues appeared histochemically to be composed of a kind of compound glycolipid or glycoprotein. Histopathologically, the biopsied rectum showed the infiltration of many histiocytes in the mucosa and ultrastructurally, the granules in these histiocytes showed many membrane-bound vacuoles of different sizes. Interestingly, the histochemical reactivity of the material in the granules was very similar to that of membranous structures in adipose tissues. In the biochemical analysis of lipids in affected adipose tissues, no marked abnormalities were found in the patients. Nasu-Hakola disease is not a typical form of lysosomal storage disease, because lysosomal enzyme activities remain normal and there is no accumulation of urinary oligosaccharides and lipids, no vacuolation of lymphocytes, and no hepatosplenomegaly. However, histochemical findings suggest that the lysosomes may be secondarily involved in this disease, and that the formation of membranous structures might be related to the disturbance of glycolipid or glycoprotein metabolisms.

Association between genetic polymorphism of the pepsinogen C gene and gastric body ulcer: the genetic predisposition is not associated with Helicobacter pylori infection

Background and aims—The genetic trait plays a part in the pathogenesis of peptic ulcer disease. To identify a DNA marker for peptic ulcer disease, the association between the restriction fragment length polymorphism (RFLP) of the pepsinogen C (PGC) gene and peptic ulcer disease was investigated. Patients and methods—One hundred and seventy seven unrelated controls, 75 patients with gastric ulcer, and 70 with duodenal ulcer were studied. PGC-RFLP was analysed by polymerase chain reaction (PCR), and the association between PGC-RFLP and peptic ulcer disease was examined. The relation between the genetic association of PGC polymorphism with peptic ulcer and Helicobacter pyloriinfection was also examined. Results—Four alleles, 480 (allele 1), 450 (allele 2), 400 (allele 3), and 310 bp (allele 4), were detected by PCR. The frequency of allele 4 was significantly higher in patients with gastric body ulcer than in controls (χ2=9.92, p<0.005). Genotypes containing allele 4 were significantly more frequent in patients with gastric body ulcer than in controls and patients with gastric angular or antral ulcer. The relative risk of gastric body ulcer associated with the presence of allele 4, compared with its absence, was 4.63 and was statistically significant (χ2=14.84, p<0.005). There were no significant differences in the allelic frequencies between H pyloripositive and H pylori negative groups in controls, patients with gastric body ulcer, or patients with gastric angular or antral ulcer. Both in H pylori negative and H pylori positive cases, there was an increased frequency of allele 4 in patients with gastric body ulcer compared with controls. Conclusions—These results suggest that there is a significant association between this genetic polymorphism at the PGC gene locus and gastric body ulcer. There are differences in the genetic aetiology between gastric body ulcer and gastric angular or antral ulcer. PGC-RFLP may be used as a genetic marker for a genetic predisposition to gastric body ulcer; this genetic predisposition is not associated with H pylori infection.

Treatment of cerebrotendinous xanthomatosis with low-density lipoprotein (LDL)-apheresis

We studied the effects of LDL-apheresis on the biochemical and clinical abnormalities of 5 patients with cerebrotendinous xanthomatosis (CTX). Levels of both cholestanol and cholesterol decreased to approximately 60% of those of pretreatment after one perfusion and gradually returned to their initial levels within 2 weeks. Improvement of clinical manifestations and regression of Achilles tendon xanthomas were detected after several perfusions, though dramatic changes could not be recognized. EEG abnormalities were improved immediately after LDL-apheresis in one patient. We conclude that LDL-apheresis may affect the serum cholestanol level and clinical manifestations in patients with CTX.