Biomedical subjects
Publications and source records attributed to M Sonobe.
A 72-year-old female with intradiploic haemangioma associated with epidural haematoma is reported. MRI finding of the lesion is described. The cause of the epidural haematoma is speculated due to fragile vessels attached directly to dura mater through the pores of the inner table of the diploë.
Japanese hereditary neuropathy with liability to pressure palsy (HNPP) patients have a deletion of one peripheral myelin protein-22 (PMP22) gene region in distal chromosome band 17p11.2 as do Caucasian patients. Japanese and Asiatic Indian CMT1A patients have a PMP22 gene duplication that results in Charcot-Marie-Tooth disease type IA (CMT1A; HMSNIA) in patients of European and Middle Eastern ancestry. About 70% of Japanese CMT1 patients have a PMP22 duplication as do Caucasians, while Japanese CMT1B, CMT2 and Dejerine-Sottas patients to not have PMP22 gene region aneuploidy. Although HNPP and CMT1A genotypes are generated simultaneously by unequal recombination that results in PMP22 gene aneuploidy in each daughter cell, only 3 Japanese HNPP probands with PMP22 deletion from a large patient population were referred to a single center compared to 18 referred CMT1A probands with PMP22 duplication. This lower HNPP frequency more likely reflects lower HNPP reproductive fitness than patient ascertainment bias because disease severity and variation in severity is about the same in CMT1A and HNPP patients and because all patients of both types were referred regardless of disease severity. These results, along with an apparently high de novo CMT1A mutation rate, suggest that common ancestors of Japanese, Asian Indians, and Caucasians carried PMP22 geneflanking sequences that enhance unequal crossing over.
It has been reported that some modified low-density lipoproteins (LDLs) such as glycated LDL and malondialdehyde-rich LDL (MDA-LDL) probably exist in the circulation. The present study was undertaken to investigate the in vitro and in vivo metabolism of MDA-LDL occurring in chronic haemodialysis patients and the effects of alpha-tocopherol on these abnormalities. MDA-LDL from haemodialysis patients was degraded more rapidly by human monocyte-derived macrophages and disappeared more slowly from the circulation when compared with LDL from healthy controls. Treatment with alpha-tocopherol at doses of 600 mg/day for 2 weeks resulted in improvement of these metabolic abnormalities depending upon the degree of return to normal MDA concentrations in LDL.
A 69-year-old male presented with sudden onset of headache. Computed tomography of the head demonstrated diffuse subarachnoid hemorrhage. Angiography showed a saccular basilar bifurcation aneurysm. Endovascular coil occlusion of the aneurysm on the same day enabled complete obliteration of the aneurysm. He did not develop vasospasm and returned home 4 months later. Early endovascular occlusion of the aneurysmal sac is an alternative method for the management of ruptured basilar bifurcation aneurysms.
A 31-year-old male developed intramedullary tumors in the medulla oblongata and the upper cervical spinal cord. He was first admitted with tetraparesis. Magnetic resonance (MR) imaging revealed a low intensity mass lesion in the medulla oblongata. The tumor was removed and diagnosed as a pilocytic astrocytoma. Nine years later, he was readmitted with motor weakness and dysesthesia in the right arm. MR imaging revealed a mass lesion in the cervical cord. This tumor was removed and diagnosed histologically as ependymoma. We suggest that the displacement of primitive spongioblasts with subsequent differentiation resulted in an astrocytoma and an ependymoma in adjacent areas.
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A sixty-two-year-old woman was diagnosed as having the mitral valve insufficiency seven months prior to admission. The patient was admitted to the hospital with complaints of right hemiparesis and aphasia. CT scan revealed an intracerebral hematoma in the left front-parietal region. Cerebral angiography disclosed an aneurysm at the distal portion of left middle cerebral artery. An increase in the amount of C reactive protein and leukocytosis indicated the presence of inflammatory lesions. Antibiotics were administered because a mycotic aneurysm was suspected. White blood cell count and C reactive protein returned to normal after treatment with antibiotics for one months. The aneurysm had disappeared on the second angiography performed after treatment. Strategy for mycotic aneurysm is still controversial. 49 reported cases in the literature since 1975 were reviewed and the efficiency of antibiotic therapy was discussed.
We have identified a new mutant Cu/Zn superoxide dismutase (SOD1) deduced from the nucleotide sequences of peripheral blood lymphocyte mRNA from Japanese patients with familial amyotrophic lateral sclerosis (FALS). Sequence analysis of reverse transcriptase-initiated PCR amplified mRNA revealed a heterozygosity indicative of one normal allele and one variant allele with a T-->A transversion. This base change led to replacement of valine by glutamic acid at position 7 of 153-residue SOD1 molecule, and produced a new restriction site for Alu I in the exon 1. Restriction fragment length polymorphism analysis confirmed the linkage of this mutation with this type of FALS. Both enzymatic activity and protein of the SOD1 were reduced in red blood cells from the patient.
We investigated the dose-dependent effects of prostaglandin E1 (PGE1) analogue, OP1206.alpha CD (OP), on motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and Na(+)-K(+)-ATPase (ATPase) activity in streptozocin-induced diabetic rats. At 10 micrograms/kg/day, OP ameliorated MNCV and NBF, but no ATPase activity, whereas at 30 micrograms/kg/day it increased MNCV and ATPase activity, but not NBF. These results suggested a possible direct metabolic effect of OP, at least at a certain dose, on ATPase activity independent of NBF. Since PGE1 exerts an effect on nerve cAMP content, we conducted an in vitro study to clarify the relationship of cAMP to the modulation of ATPase activity in diabetic nerves. We studied sciatic nerves isolated from 53 rats with streptozocin-induced diabetes that had exhibited hyperglycemia for 6 wk. OP increased the activity of ATPase and the accumulation of cAMP in a dose-dependent manner. Dibutyryl cAMP, a cAMP analogue, and aminophyline, which increases nerve cAMP content, enhanced ATPase activity in a dose-dependent manner. In addition, the increased activity of ATPase in diabetic nerves produced by OP was suppressed by a protein kinase inhibitor, H8. These results suggest that ATPase activity in diabetic nerves might be regulated or modified by cAMP and, possibly, by protein kinase A, a finding that is important for clarifying the pathogenesis of diabetic neuropathy and for developing new approaches to treatment.
Two cases of spontaneous dissecting aneurysm localized to the anterior cerebral artery are reported. Both patients experienced severe headaches, followed by symptoms of cerebral ischemia. In the first case, the dissecting aneurysm showed an angiographic appearance resembling a saccular aneurysm of the anterior communicating artery, and the diagnosis of dissecting aneurysm was confirmed at operation. The second case was treated conservatively, and the diagnosis was reached by repeat angiographic studies.
In view of the possible implication of multifactorial mechanisms in the pathogenesis of diabetic neuropathy, the aldose reductase inhibitor (ARI), Statil, which ameliorates abnormal sorbitol or myo-inositol metabolism in diabetic nerves, and the prostaglandin E1 (PGE1) analogue, OP1206.alpha CD (OP), which improves diabetic vascular derangements, were administered simultaneously for 2 months to streptozocin (STZ)-induced diabetic rats with 5 months' duration of diabetes, and the effects on sciatic motor nerve conduction velocity (MNCV), Na(+)-K(+)-adenosine triphosphatase (ATPase) activity, and morphology of myelinated nerve fibers (MNF) were compared with the effects of a monotherapy with OP. The combination regimen ameliorated abnormal nerve sorbitol and myo-inositol levels and normalized decreased MNCV and enzyme activity. In contrast, neither sorbitol nor myo-inositol metabolism was ameliorated, and only insufficient improvement of MNCV and morphology of MNF was obtained with a monotherapy with OP. In addition, the combination therapy reversed both a decrease in the percent of large MNF and an increase in the percent of small MNF in diabetic rats, whereas a monotherapy with OP reversed only a decrease in the percent of large MNF. The results might suggest that a multiple-drug therapy with different mechanisms of action has greater effects on diabetic neuropathy than a single-drug therapy and is worthy of clinical consideration.
The effects of vitamin E on the progress of atherosclerosis in patients on hemodialysis was investigated clinically using ACI. There was a significant suppression of the increase in ACI in group A, compared to group B, at the time of observation in each year. On the other hand, no significant changes were noted in BWD, CTR, BP and blood chemical examination, except that the level of MDA was significantly decreased in group A as compared with that in group B 4 years later. Since ACI is an index representing atherosclerosis, the results of this study seemed to suggest that the progress of atherosclerosis was suppressed by long-term administration of vitamin E in patients on hemodialysis.
An investigation was undertaken to determine which plasma factors from normal controls and patients with chronic renal failure (CRF) exert have inhibitory effects on the activity of lipoprotein lipase (LPL) purified from heparinized human plasma by using an accurate LPL assay system. Inhibitors of LPL were found to be present in the plasma. The inhibition of the LPL activity was significantly greater in CRF patients than in normal controls. Following hemodialysis (HD), the same concentration of uremic plasma led to less inhibition. The inhibitors existed only in lipoprotein deficient plasma (LPDS), which demonstrated an LPL-inhibitory activity at extremely high concentrations with a significant difference between the patients and normal controls. There was no difference between the two groups at low concentrations. A specific inhibitory effect on LPL in LPDS was noted in the 7S and 4S fractions separated by gel filtration employing Sephacryl S-200 column chromatography. The inhibitory effect of the 7S fraction was found to be dependent on the concentration, and the difference between the two groups was similar to that for LPDS. The results obtained in the present study suggest that the plasma from CRF patients exhibited a strong inhibitory action on the LPL activity as compared to the plasma from normal controls, and the inhibitory action was due primarily due to poor excretion of dialyzable inhibitors.
We investigated the effect of platelet-activating factor (PAF) and of the PAF specific antagonist CV-6209 on plasma lipid metabolism, and particularly on post-heparin plasma lipolytic activity in male Wistar rats. Lipoprotein lipase (LPL) activity was enhanced by intravenous injection of PAF before intravenous injection of heparin when the PAF dose was low (0.2 micrograms/kg). PAF activated hepatic triacylglycerol lipase (HTGL) activity dose-dependently. Plasma triacylglycerols (TG) significantly decreased with the activation of LPL and/or HTGL. Plasma total cholesterol (TC) and phospholipid (PL) levels decreased at a low dose of PAF (0.2 micrograms/kg), but increased when higher doses were used. The PAF antagonist CV-6209 partially reversed the PAF induced effects on HTGL, TC and PL.
An oral prostaglandin E1 (PGE1) analogue, OP-1206.alpha-CD, was given to rats with streptozocin (STZ)-induced diabetes to examine the therapeutic effects of OP-1206 on short-term and long-term diabetic neuropathy and its action mechanism with special reference to nerve Na(+)-K(+)-ATPase activity. In the short-term experiment, OP-1206 was administered daily to diabetic rats in 3- and 30-mg/kg doses for 4 wk from the day of STZ injection. In the long-term study, 10 micrograms/kg OP-1206 was also given daily for 8 wk from 7 mo after induction of diabetes. The compound improved decreased sciatic motor nerve conduction velocity in both short-term and long-term diabetic rats. The nerve Na(+)-K(+)-ATPase activity of diabetic rats, reduced by 40% compared with controls, was reversed to the level of controls in both experiments, whereas weight loss and hyperglycemia were unchanged, and neither nerve sorbitol accumulation nor myo-inositol depletion was corrected. In a morphometric analysis of myelinated nerve fibers (MNFs) in long-term diabetes, the mean diameter of the largest 10% of MNFs was significantly reduced in untreated diabetic compared with control rats, but OP-1206 completely reversed this reduction. The results suggest that OP-1206 ameliorates a decrease in nerve Na(+)-K(+)-ATPase activity without any effect on nerve myo-inositol level and that the compound may be not only a potent therapeutic agent for the treatment of diabetic neuropathy but also a useful research tool to investigate the mechanism of nerve Na(+)-K(+)-ATPase activity regulation.
A case of spinal cord sarcoidosis was reported with special reference to MRI findings. A 15-year-old man was admitted to our hospital because of gait disturbance for last six months. Neurological examination on admission showed spastic paraparesis and posterior column signs. MRI of the cervical spinal cord revealed diffuse swelling and low intensity signal in T1-weighted sequences, diffuse high intensity signal in T2-weighted, and multiple micro-nodular lesion in Gd-DTPA enhanced T1-weighted. At first multiple sclerosis was suspected, although the data of cerebrospinal fluid was not suggestive. Four weeks after admission general fatigue, fever, cough, and headache appeared and the neurological symptoms got worse. Chest film and CT revealed diffuse small nodular shadows in the lung field. Abdominal ultrasonography and CT showed hepatosplenomegaly. The general condition became worse in spite of antibiotic and antituberculotic drug therapy, but remitted spontaneously in four weeks. MRI findings also exacerbated and improved during the same period, being compatible with neurological manifestations. The diagnosis of sarcoidosis was made by transbronchial lung biopsy which revealed sarcoid granuloma. Multiple small nodules on Gd-DTPA enhanced T1-weighted MRI had not been reported in patient with spinal cord sarcoidosis.
A female who had had no previous cerebrovascular events suffered a subarachnoid hemorrhage and was referred to our hospital. Angiography revealed an anterior communicating artery aneurysm and bilateral occlusion of the middle cerebral artery at its origin. She exhibited mild ischemic symptoms after clipping of the aneurysm, possibly as a consequence of disturbance of the collateral blood flow during surgery. This is the third such case reported in the literature.
The effect of a newly developed oral agent, prostaglandin E1 (PGE1) analogue TFC 612, on diabetic neuropathy was studied by giving it for 6 wk to streptozocin-induced diabetic rats that had been diabetic for 3 mo and was compared with the effects of aldose reductase inhibitor ONO 2235. Although both compounds improved decreased motor nerve conduction velocity, the effect of TFC 612 continued during the 6 wk of treatment, whereas that of ONO 2235 became weaker from wk 4. The abnormality in sciatic nerve sorbitol and myo-inositol levels was reversed with ONO 2235, whereas it was unchanged with TFC 612. With the laser Doppler flowmetry technique, a decrease in the sciatic nerve blood flow in diabetic rats was shown to improve with both compounds, but TFC 612 had a greater effect than ONO 2235, and the increased lactate level of the diabetic nerve was corrected with both compounds, suggesting that both may be associated with the amelioration of ischemia in the diabetic endoneurium. Both TFC 612 and ONO 2235 partially but significantly normalized decreased fiber size in diabetic rats. On the other hand, TFC 612 completely normalized the dilated lumen area in diabetic rats, whereas ONO 2235 did not. These results suggest that the PGE1 analogue TFC 612 has a significant effect on diabetic neuropathy, possibly via vasotropic action, and may be a potent compound for the treatment of diabetic neuropathy.