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Biomedical subjects

F Kanda

Publications and source records attributed to F Kanda.

At least 55 records · Page 3Linked to original sources

Dual-energy X-ray absorptiometry in neuromuscular diseases.

Body components were measured noninvasively in patients with neuromuscular disease by using dual-energy X-ray absorptiometry (DXA), capable of separately analyzing fat, bone, and muscle content. In all patients with muscle atrophy of myogenic or neurogenic origin, muscle mass was markedly reduced. Although all three components (fat, muscle, and bone) were decreased in neurogenic atrophy patients, fat mass alone was increased significantly in myogenic atrophy patients. The fat/muscle ratio (f/m) was significantly higher in myogenic atrophy patients than in the normal controls and neurogenic atrophy patients. The higher f/m ratio in myogenic atrophy patients seems to reflect a marked fat infiltration into atrophied skeletal muscles of patients with primary muscular disease. Using DXA, it is possible to distinguish clearly between myogenic atrophy from neurogenic atrophy, opening the way to an evaluation of the severity of quantitative and qualitative muscle changes in neuromuscular disease.

Absorptiometry, Photon↗

Characteristics of dynamic mutation in Japanese myotonic dystrophy.

To study the characteristics, if any, of unstable CTG repeat sequence in Japanese myotonic dystrophy (DM), we analyzed DNA from 351 at risk individuals (including affected and non-affected carriers and their descendants) from 105 families in Japan. A total of 93 DM families (196 affected and 116 unaffected individuals), including 84 DM parent-child pairs (44 father-child and 40 mother-child pairs), were examined, many of which had been previously tested by linkage analysis. We detected unstable CTG repeat mutations between 0.15 kb and 8.7 kb in size. The size of the mutation correlated with the age of onset of symptoms. There was a significant difference in DM allele size among the four groups (congenital, juvenile onset, classical, and minimal). Congenital DM had on average the largest repeat sizes. Comparison of parent-child pairs showed that most offspring had a larger repeat size than their parents, with only 2 of 84 showing a definite decrease in repeat size. The correlation coefficients for maternal and paternal transmission were 0.41 and 0.15, respectively. The parental age (maternal and paternal) did not correlate with intergenerational change of repeat. These observations are similar to those reported in Caucasians.

Adolescent↗

Vasopressin inhibits calcium-coupled sodium efflux system in rat brain.

Centrally released vasopressin plays an important role in the regulation of brain water and electrolyte composition and can affect brain intracellular pH and ATP synthesis in vivo. In this study, we evaluated the effects of [Arg8]vasopressin (AVP) on the Na(+)-Ca2+ exchanger, an important pathway in the regulation of cell Ca2+ concentration. It was found that AVP inhibited the Na(+)-Ca2+ exchanger in rat brain synaptosomes. This effect was completely blocked by the vasopressin V1-receptor antagonist d(CH2)5[(O-Me) Tyr2, Arg8]vasopressin. In addition, the vasopressin V2-receptor agonist 1-desamino-8-D-arginine vasopressin had no effect on the Na(+)-Ca2+ exchanger in rat brain synaptosomes. Depletion of intracellular Ca2+ by caffeine also had no effect on the effect of AVP on the Na(+)-Ca2+ exchanger. Na+ uptake by other pathways was also evaluated. It was found that AVP had no effect on Na+ uptake by pathways other than the Na(+)-Ca2+ exchanger. It is concluded that AVP inhibits the Na(+)-Ca2+ exchanger in neuronal membranes through vasopressin V1 receptors. Since this pathway is important in the regulation of cell volume and cytosolic Ca2+ in excitable tissue, AVP may impair neuronal cell repolarization in the central nervous system.

Animals↗

Adrenogenital syndrome caused by an androgen-producing adrenocortical tumor.

We describe here a typical case of virilizing adrenocortical tumor. A 23-year-old Japanese woman had her male-like musculature, hirsutism, the absence of breast development and marked clitoromegaly. Adrenal androgens were remarkably elevated, with plasma dehydroepiandrosterone sulfate 2,752 micrograms/dl, plasma testosterone 250 ng/dl and urinary 17-ketosteroids 203.4 mg/day. A well-encapsulated tumor approximately 7 cm in diameter was detected in the left adrenal gland by computed tomography, magnetic resonance imaging and arteriography. The tumor was surgically resected and histologically diagnosed as a benign adrenocortical adenoma. The elevated adrenal androgens returned to normal postoperatively with amelioration of her masculinized clinical features.

Adenoma↗

Glycogenosis type V (McArdle's disease) with hyperuricemia. A case report and clinical investigation.

A 28-year-old male with glycogenosis type V associated with continuous hyperuricemia during mild daily activities is reported. An aerobic exercise test using a bicycle ergometer revealed that purine metabolites, i.e., ammonia, inosine, hypoxanthine and xanthine, were transiently increased by the exercise and that a subsequent increment in uric acid continued until the following day. The accelerated purine degradation by the muscle exercise was thus shown to be able to cause the overt hyperuricemia in a patient with glycogenosis type V. Therapeutic use of fructose for glycogenosis was disappointing due to fructose-induced hyperuricemia. A search for myogenic hyperuricemia is essential for therapeutic trials.

Adult↗

Cytotoxic brain edema: assessment with diffusion-weighted MR imaging.

To determine whether cytotoxic brain edema is associated with a decrease in diffusion, it was induced in rats, in the absence of ischemia, with an established model of acute hyponatremic encephalopathy. Cytotoxic brain edema secondary to acute hyponatremia was induced with intraperitoneal injections of 2.5% dextrose in water and subcutaneous injection of arginine-vasopressin. Coronal spin-echo magnetic resonance (MR) images were obtained with and without strong diffusion-sensitizing gradients before and after induction of acute hyponatremia. The apparent diffusion coefficient (ADC) was measured at two coronal section locations. In hyponatremic rats, the brain ADC was significantly reduced (P = .0153 and .0001) and was positively correlated with increased total brain water content (P = .0011). Plots of ADC versus total brain water showed a statistically significant inverse linear relationship between ADC and increasing brain water at the anterior coronal section location. The results indicate that the ADC may be a sensitive indicator of cytotoxic brain edema and thus may enable quantitative evaluation of such edema with diffusion-weighted MR imaging.

Animals↗

Atrial natriuretic peptide inhibits amiloride-sensitive sodium uptake in rat brain.

Both atrial natriuretic peptide (ANP) and its receptors are present in the central nervous system, but effects of ANP on brain are unclear. In the present study, we evaluated both the effects of ANP on sodium uptake, and a possible effector mechanism, the putative intracellular second messenger guanosine 3',5'-cyclic monophosphate (cGMP), in rat brain synaptosomes. In the presence of ANP (10(-7) M), the basal level of sodium uptake in synaptosomes was reduced (n = 6) from the control value of 1.90 +/- 0.06 to 1.73 +/- 0.04 (SE) nmol/mg protein at 5 min, P less than 0.05. The observed reduction of sodium uptake by ANP was not influenced by blockade of the other important pathways for sodium uptake. Addition of either a sodium channel blocker (tetrodotoxin) or an inhibitor of Na(+)-K(+)-adenosinetriphosphatase (ATPase) (ouabain) did not affect sodium uptake in the presence of ANP. However, the reduction of sodium uptake was completely blocked by addition of amiloride. These findings suggest that ANP reduced sodium uptake via inhibition of an amiloride-sensitive pathway for sodium uptake. cGMP is a major intracellular second messenger for ANP in other tissues. We found that after stimulation with 10(-7) M ANP, synaptosomal cGMP increased significantly from 58.0 +/- 9.5 to 73.5 +/- 10.6 fmol/mg protein (P less than 0.01). When an analogue of cGMP, 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP), was added to synaptosomes, amiloride-sensitive sodium uptake was again inhibited, by a similar amount as occurred with ANP. It appears that in rat brain, ANP inhibits amiloride-sensitive sodium uptake via a pathway involving intracellular production of cGMP.

Amiloride↗

Anaesthetic management of dilated cardiomyopathy with severe ventricular dysrhythmias.

A 67-year-old man with dilated cardiomyopathy underwent subtotal gastrectomy. The risks due to anaesthesia and surgery were considered to be very high because of the severe dysrhythmias and renal dysfunction. Anaesthesia was induced with fentanyl and midazolam and maintained with additional fentanyl, midazolam, and 60% nitrous oxide. Dobutamine, dopamine, lignocaine and a temporary pacemaker were used to control cardiovascular responses during surgery. Mild hypotension and tachycardia occurred, but neither circulatory failure nor other major complications were observed during and after the operation.

Aged↗

Acute autonomic and sensory neuropathy: a case report.

A female patient with acute autonomic and sensory neuropathy is described. Urinary disturbance developed rapidly and was followed by orthostatic syncope, absence of lacrimation, salivation and sweating, and sensory impairment. Muscle strength had been consistently normal despite diffuse muscular atrophy. Marked decrease in the number of small myelinated and unmyelinated fibres was revealed in biopsied sural nerve. Eighteen months after the onset, her autonomic symptoms have partially improved.

Acute Disease↗

Somatosensory evoked potentials in acute renal failure: effect of parathyroidectomy.

Effects of acute renal failure (ARF) on somatosensory evoked potentials (SEP) were studied in rats. Cervical and cortical SEPs were measured both before and after bilateral ureteral ligation. A significant augmentation of amplitudes and an increase in latencies of the cortical SEP were observed in ARF. The peripheral nerve conduction velocities were unchanged. Serum parathyroid hormone (PTH) levels in uremic rats were significantly elevated after the bilateral ureteral ligation. In previously parathyroidectomized rats, the bilateral ureteral ligation had no effects on amplitudes of SEP or serum PTH levels.

Acute Kidney Injury↗

Elucidation of chemical compounds responsible for foot malodour.

Short-chain fatty acids from the socks and feet of subjects either with strong foot odour or with weak or no foot odour were extracted with ethyl ether, and then analysed by gas chromatography/mass spectrometry (GC/MS). Short chain fatty acids were found in greater amounts from those subjects with strong foot odour. Iso-valeric acid was present in all the subjects with foot odour but was not detected in those without. Olfactory evaluations of the various short-chain fatty acid solutions were in agreement with the GC/MS analyses. By incubating sweat and lipid from subjects with strong foot odour, we succeeded in reproducing the foot malodour. GC/MS analyses of reproduced foot odour revealed that short-chain fatty acids were present in a similar composition to that found in vivo.

Adult↗

A case of mitochondrial myopathy, encephalopathy and lactic acidosis due to cytochrome c oxidase deficiency with neurogenic muscular changes.

An 18-year-old male with mitochondrial myopathy, encephalopathy and lactic acidosis was studied by electromyography (EMG) along with histological and biochemical studies on his biopsied muscle. Mitochondrial cytochrome c oxidase deficiency with a decrease in the amounts of the subunits 2, 6, and 7 was discovered. Although no apparent symptoms of peripheral neuropathy were present, EMG revealed high-amplitude motor unit action potentials with a reduced interference pattern and the histochemical study revealed fiber type grouping without grouped atrophy. These findings indicated lower motor neuron damage, probably due to the mitochondrial disorder, followed by reinnervation. Coenzyme Q10 administration was effective in reducing both the lactate and pyruvate levels and for recovering the muscle atrophy.

Acidosis, Lactic↗

Calcitonin gene-related peptide enhances spontaneous acetylcholine release from the rat motor nerve terminal.

The effect of synthetic rat calcitonin gene-related peptide (rCGRP) on neuromuscular transmission was examined in a superfused rat phrenic nerve-diaphragm preparation using an intracellular microelectrode technique. The superfusion with rCGRP (10(-8) to 2 x 10(-7) M) caused significant increases in the frequency of miniature endplate potentials (MEPPs). It, however, had no effect on the resting membrane potential, amplitude of MEPPs, or acetylcholine quantum size and content. Enhancement of spontaneous acetylcholine release from the motor nerve terminal by rCGRP was demonstrated.

Acetylcholine↗

Intracytoplasmic inclusion bodies of the thalamus and the substantia nigra, and Marinesco bodies in myotonic dystrophy: a quantitative morphological study.

Intracytoplasmic inclusion bodies of the thalamus and the substantia nigra, and Marinesco bodies have been studied in four patients with myotonic dystrophy (MyD), eight patients with other neurological diseases (control A), and eight patients without neurological diseases (control B). The percentages of the affected cells were calculated by dividing the number of neurons including intracytoplasmic inclusion bodies of the thalamus and the substantia nigra, and Marinesco bodies, by the total cell count in these respective regions. Statistical analyses were performed with regard to the frequency of these bodies by using Student's t test. There was a significantly higher incidence of intracytoplasmic inclusion bodies of the thalamus (13.2% versus 0.7%, P less than 0.001) and the substantia nigra (20.4% versus 2.7%, P less than 0.001), and Marinesco bodies (37.4% versus 4.1%, P less than 0.001) in patients with MyD than in controls A and B. From our observations, it is suggested that the presence with a high frequency, in combination, of these bodies is not an incidental finding but may have an intimate and important relationship with the pathogenesis of MyD, and may be a conspicuous and diagnostically important feature of MyD.

Adult↗

[A case of adrenomyeloneuropathy with localized cerebral white matter degeneration].

A male with an atypical adrenomyeloneuropathy is described, who developed spastic paraparesis at the age of 37. Because his gait deteriorated further and he had a bladder dysfunction, he was admitted to National Sanatorium Hyogo Central Hospital at the age of 51. A diagnosis of adrenomyeloneuropathy was supported by increased level of very long chain fatty acids in plasma. He became demented and suffered from grand mal seizures during the last one year of his life. CT scan showed symmetrical hypodense lesions in the centrum semiovale. He died of pneumonia and renal failure at the age of 53. Autopsy revealed symmetrical degeneration throughout the corticospinal tracts from cerebral white matter to lumbar spinal cord. Degeneration of the optic radiation, posterior half of the corpus callosum, thalamus, cerebellar white matter, and gracile tract in high cervical segments were also observed. In these area, there was a loss of myelin and axon with marked gliosis and foamy macrophages, as well as mild perivascular cuffing. In our case, symmetrical and well-defined lesion in cerebral white matter is atypical for adrenomyeloneuropathy, while destruction of the gracile tracts is not a feature of adrenoleukodystrophy. In addition, well-demarcated "pseudosystemic" type of fiber tract degeneration appears to be different from a feature of primary demyelination which has been considered to be an essential alteration of adrenoleukomyeloneuropathy-complex. We propose another hypothesis, therefore, that neurons are primarily altered, thereby leading to the degeneration of myelins in this disease.

Adrenoleukodystrophy↗

Somatosensory evoked potentials in patients with hypocalcaemia after parathyroidectomy.

The effects of hypocalcaemia on somatosensory evoked potentials (SEPs) were studied in five patients after parathyroidectomy. Despite normal latencies the mean value of amplitudes of the SEPs in hypocalcaemic patients was greater than that in normocalcaemic subjects. Recovery functions of the SEPs showed a significant decrease in hypocalcaemic patients at interstimulus intervals of about 10 ms compared with those in normocalcaemic patients and in normal volunteers. Recovery functions appear to be a valid indicator of synaptic efficacy, especially for evaluation of the reduction in conduction efficacy of the central nervous system in hypocalcaemia.

Aged↗

Neuropathological changes of the brain in myotonic dystrophy--some new observations.

Brain autopsy materials from 2 patients with myotonic dystrophy (MyD) were studied. The results obtained in these 2 cases were quite similar. Besides thalamic inclusion bodies and minor abnormalities in gyral architecture with a disordered cortical cellular arrangement, some new observations have been made. First, no more than one intracytoplasmic inclusion body per cell was present in the cerebral cortex, the thalamus, the caudate nucleus and the putamen; this inclusion body was oval or elongated with smooth, sharply defined contours and was usually located at the periphery of the cell. Second, irregular intracytoplasmic inclusion bodies, often multiple and not surrounded by a halo, were found at the periphery or within accumulations of neuromelanin granules in the pigmented cells of the substantia nigra. All the bodies described above stained highly eosinophilic with hematoxylin-eosin and the ultrastructure of the bodies in the thalamus and the substantia nigra was almost the same; these bodies were composed of stacks of alternating parallel, light and dark rectilinear profiles oriented perpendicularly to the longitudinal axis of the bodies. Third, Marinesco bodies were observed with a very high frequency in the pigmented cells of the substantia nigra.

Aged↗

Substrate recognition of isopeptidase: specific cleavage of the epsilon-(alpha-glycyl)lysine linkage in ubiquitin-protein conjugates.

The structural chromatin protein A24 (uH2A) is a conjugate of histone H2A and a non-histone protein, ubiquitin. Eukaryotic cells contain an enzyme, generically termed isopeptidase, which can cleave A24 stoichiometrically into H2A and ubiquitin in vitro. Isopeptidase, free of proteinase activity, has been partially purified from calf thymus by ion-exchange chromatography, gel filtration and affinity chromatography, and analyzed for its substate specificity. There are three major types of isopeptide bonds besides the epsilon-(alpha-glycyl)lysine bond between H2A and ubiquitin; namely, the disulfide bridge, the aldol and aldimide bonds and the epsilon-(gamma-glutamyl)lysine crosslink. Under conditions where A24 was completely cleaved into H2A and ubiquitin, none of these naturally occurring isopeptide bonds was cleaved by isopeptidase. Furthermore, the bonds formed in vitro by transglutaminase reaction between casein and putrescine, through the gamma-NH2 of glutamine residue and the NH2 of putrescine, were not cleaved by the enzyme. The enzyme also failed to cleave the glycyl-lysyl and other orthodox peptide linkages within proteins. Among various proteins examined, the substrates for isopeptidase reaction were confined to conjugates between ubiquitin and other proteins, formed through epsilon-(alpha-glycyl)lysine bonds. Since ubiquitin released by isopeptidase is re-usable for an ATP-dependent conjugation with other proteins, its carboxyl terminal -Gly-Gly-COOH most likely is preserved intact, and is not blocked. These results suggest that isopeptidase specifically recognizes and cleaves the epsilon-(alpha-glycyl)lysine bond. A possible biological significance of this enzyme is discussed.

Animals↗