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Biomedical subjects

M Fukui

Publications and source records attributed to M Fukui.

At least 19 recordsLinked to original sources

Immunosuppressive-associated leukoencephalopathy in organ transplant recipients.

Immunosuppressive-associated leukoencephalopathy is a significant complication of cyclosporine (CsA) or tacrolimus therapy. However, the precise time of onset, role of putative risk factors, differences, if any, in presentation in various types of organ transplantation and outcome of this entity, remain poorly defined. Fifty cases of immunosuppressive-associated leukoencephalopathy reported in the literature in organ transplant recipients, were reviewed. Of 50 cases, 31 occurred in liver, 8 in renal, 6 in lung, and 5 in heart transplant recipients. Median time to onset was 28 days (range 3-1512 days); 82% occurred within 90 days of transplantation. Lesions tended to occur earlier in the liver transplant recipients, compared with other organ transplant recipients (median 9 vs. 29 days, P=.19). Seizures 74%, altered mental status 50%, and visual abnormalities 28% were the most frequently presenting features. Ten percent of the patients had fever with no documented source of infection. Systemic hypertension (P=.001), and lesions in the presence of therapeutic drug levels (P=.11) were more likely to occur with CsA than tacrolimus. Neuroimaging and clinical abnormalities were reversible on cessation or reduction of CsA or tacrolimus in all but two cases. Resolution of neurologic signs/symptoms occurred a median of 4 days and neuroimaging abnormalities in a median of 20 days on reduction/cessation of the drug. Immunosuppressive-associated leukoencephalopathy is a unique entity that can usually be diagnosed on the basis of its distinctive time of onset, and clinical and neuroimaging characteristics, and it is potentially reversible if promptly diagnosed. Despite identical clinical presentation of this syndrome in the recipients of CsA and tacrolimus, above noted variations in risk factors suggest that a difference in pathophysiologic mechanism may exist.

Cyclosporine

Difference of the liver and kidney in glycine conjugation of ortho-substituted benzoic acids.

The relative importance of the liver and kidney for glycine conjugation of ortho-substituted benzoic acids was investigated. Glycine conjugation of ortho-substituted benzoic acids was investigated in mouse liver and kidney mitochondria. The extent of glycine conjugation of benzoic acids with the halogen group decreased in the order F > Cl > Br > I. The conjugation of salicylic acid with glycine took place in only the kidney. 2-Methoxybenzoic acid exhibited no activity in the liver and kidney. The difference in glycine conjugation of ortho-substituted benzoic acids was observed between liver and kidney. The kidney was more active in glycine conjugation of ortho-substituted acids than the liver. In addition, the relationship between glycine conjugation and the chemical structure of ortho-substituted acids was examined in the liver and kidney. The size of the substituent had a far greater influence over glycine conjugation in the liver and kidney. Glycine conjugation was also dependent on the substituent electronegativity. It may be important that the substrates undergoing glycine conjugation contain a flat region coplanar to the carboxylate group.

Animals

Human mast cells express the hyaluronic-acid-binding isoform of CD44 and adhere to hyaluronic acid.

CD44 is expressed in various isoforms on multiple cell lineages including those of hematopoietic origin and is believed in part to mediate cell adhesion to hyaluronic acid. Elevated levels of soluble CD44 (sCD44) have been identified in the serum of some patients with specific neoplasms. We thus sought to determine whether human mast cells express functional CD44 and whether sCD44 might be associated with systemic mast cell disease. Using a standard assay, CD34(+)-derived cultured human mast cells were first demonstrated to adhere to hyaluronic-acid-coated surfaces. Human mast cells were then found by flow cytometry to express CD44S, but not the v5, v6, v7, and v8 isoforms, and to shed CD44S following activation induced by PMA or aggregation of FcvarepsilonRI. However, CD44S was not found to be consistently elevated in serum obtained from patients with mastocytosis or individuals experiencing anaphylaxis. Thus, human cultured mast cells express and shed CD44S, which appears to mediate the attachment of these cells to hyaluronic acid.

Anaphylaxis

Pneumocephalus associated with aqueductal stenosis: three-dimensional computed tomographic demonstration of skull-base defects.

Ventriculoperitoneal (VP) shunt placement in patients with aqueductal stenosis has recently been reported as a cause of pneumocephalus. We report on a patient with pneumocephalus associated with aqueductal stenosis treated by VP shunting. A 29-year-old woman who had undergone a shunt operation for aqueductal stenosis 7 years previously sustained a whiplash injury in a minor traffic accident. Computed tomography (CT) revealed massive subdural pneumocephalus, and three-dimensional reconstructions of CT images clearly demonstrated defects in the skull base overlying the ethmoid sinuses. Both endoscopic III ventriculostomy and placement of external ventricular drainage were came free of symptoms and rhinorrhea ceased. Three-dimensionally reconstructed CT images were useful in detecting the extent of the patient's skull base defect. III Ventriculostomy was not effective in this case. Direct closure of the skull base by craniotomy was not necessary, and a programmable valve system was effective in preventing recurrence of either pneumocephalus or rhinorrhea.

Adult

Normal diffusion-weighted imaging in cerebral air embolism complicating angiography.

We report a case of cerebral air embolism resulting from accidental air infection during cerebral angiography. A 60-year-old man was accidentally injected with air via the left subclavian artery. Angiography demonstrated air within the basilar artery. The patient showed signs of posterior circulation ischaemia (confusion, blindness, gaze palsy and hemiparesis). However, MRI, including diffusion-weighted imaging, showed no abnormality 4 h later. The patient was treated with hyperbaric oxygen within 5 h of the embolism. All symptoms and signs resolved completely within a week.

Brain

Association between type 1 diabetes age-at-onset and intercellular adhesion molecule-1 (ICAM-1) gene polymorphism.

We investigated the intercellular adhesion molecule-1 (ICAM-1) gene polymorphism in 90 patients with young-onset type 1 diabetes, 74 with adult-onset type 1 diabetes, and 171 control subjects. The distribution of C-T genotypes and allele frequencies in exon 6 of the ICAM-1 gene was significantly different between adult-onset type 1 diabetes patients and controls (chi(2) = 9.76, p = 0.0076), and between patients with adult-onset and young-onset type 1 diabetes (chi(2) = 11.28, p = 0.0036). In contrast, we failed to detect any association between patients with young-onset type 1 diabetes and controls. Our data suggest that ICAM-1 exon 6 gene polymorphism affects the age-at-onset of type 1 diabetes and that different pathogenetic mechanisms may exist between young-onset and adult-onset type 1 diabetes.

Adolescent

Cerebellar neuroblastoma in an infant.

A cerebellar neoplasm in an 8-month-old boy is reported. While this tumour was composed of small cells and had regions resembling desmoplastic medulloblastoma, it showed ultrastructural neuronal characteristics including bundles of microtubules in the cell processes, numerous synaptic vesicles, and occasional abortive or complete synapses. These characteristic features warranted the diagnosis of a neuroblastoma of the cerebellum. The nature of this rare intraparenchymal tumour in infants is also briefly discussed.

Cerebellar Neoplasms

Metastatic spinal intramedullary germinoma with elevated cerebrospinal fluid chorionic gonadotropin: a case report.

We treated a patient whose unusual recurrent germinoma illustrates the diagnostic value of measuring human chorionic gonadotropin beta subunit (HCG-beta) in cerebrospinal fluid (CSF) and serum. A 25-year-old man with a suprasellar germinoma and ventricular dissemination was treated successfully with systemic chemotherapy and cranial irradiation. Six years later he developed progressive numbness and weakness in both upper extremities. Magnetic resonance imaging (MRI) disclosed an intramedullary spinal cord tumor in the cervical region. The CSF concentration of HCG-beta was elevated and exceeded that in serum. After completion of systemic chemotherapy and spinal irradiation, symptoms subsided and the tumor was no longer evident on MRI. Based on the patient's history and the rapid response of the tumor to treatment, the spinal cord tumor was considered a metastatic intramedullary spinal germinoma representing CSF dissemination via the central canal.

Adult

Magnetoencephalographic analysis of periodic lateralized epileptiform discharges (PLEDs).

OBJECTIVE: To clarify the spatial and temporal distribution of the electroencephalographic (EEG) pattern termed 'periodic lateralized epileptiform discharges' (PLEDs), we performed magnetoencephalography (MEG) to analyze PLEDs in a patient with a right parietal metastasis associated with meningeal carcinomatosis. METHODS: A 37-channel biomagnetometer was used to simultaneously record the EEG and MEG. Equivalent current dipole (ECD) source localization was calculated based on a single-dipole model and mapped onto a magnetic resonance image. Single-photon emission computed tomography with technetium-99-hexamethyl-propyleneamine oxime (HMPAO-SPECT study) was also performed during both presence and absence of PLEDs according to an EEG monitor. RESULTS: By EEG the PLEDs, predominantly right-sided, consisted of a typical negative triphasic spike followed by a slow negative wave. By MEG the PLEDs had a sequence with 3 distinct components. ECDs in the 3 components were localized to the cortex around the lesion, although exact localization and dipole direction varied between components. HMPAO-SPECT demonstrated hypoperfusion of the lesion and adjacent cortex during both quiescence and appearance of PLEDs. CONCLUSION: Our results indicate that PLEDs originated from the hypoperfused cortex surrounding the lesion.

Brain Mapping

High incidence of hyponatremia in patients with ruptured anterior communicating artery aneurysms.

We studied the incidence and timing of hyponatremia (Na < 135 mEq l-1) after subarachnoid hemorrhage (SAH) with special reference to ruptured anterior communicating artery (A-com) aneurysms. Hunt and Kosnik (HK) grading, symptomatic vasospasm in A-com aneurysm, and hydrocephalus were analyzed for connections to hyponatremia in 55 patients with ruptured A-com aneurysms, 65 with ruptured internal cerebral artery (ICA) aneurysms, and 49 with ruptured middle cerebral artery (MCA) aneurysms. Hyponatremia occurred in 28 (51%) of 55 patients with A-com aneurysms and in nine (18%) of 49 patients with MCA aneurysms. Severe hyponatremia (Na < 130 mEq l-1) occurred in 16 patients (29%) in the A-com group, four patients (6%) in the ICA group, and three patients (6%) in the MCA group. The A-com aneurysm group had a significantly higher incidence of mild hyponatremia (p < 0.01) and severe hyponatremia (p < 0.001) than other groups. Among A-com cases, hyponatremia occurred significantly more often in HK grade III and IV cases (p < 0.05), in cases with vasospasm (p < 0.001), and in cases with hydrocephalus (p < 0.01). Respective days of onset for symptomatic vasospasm and for hyponatremia were day 7.6 +/- 4.4 and day 10.6 +/- 5.8 following SAH, representing a 3-day delay for hyponatremia (p < 0.05). In most patients hyponatremia resolved within 28 days following SAH. Hyponatremia occurred more often with A-com aneurysms, possibly because of vasospasm around the A-com or hydrocephalus causing hypothalamic dysfunction. Since hypervolemic therapy can cause hyponatremia, particularly careful observation is required during such therapy in patients with A-com aneurysm.

Aneurysm, Ruptured

Vascular endothelial growth factor and malignant transformation of a meningioma: case report.

Although meningiomas are common benign intracranial tumors which grow slowly, we occasionally encountered aggressive or malignant ones. One of these cases showed an interesting relationship to vascular endothelial growth factor (VEGF). A 39-year-old woman underwent resection of a sphenoid ridge meningioma; the residual tumor showed evidence of malignant transformation 14 years later. We immunohistochemically examined six successive surgical specimens plus the autopsy specimen of this patient's tumor for proliferative potential, vascularity, and expression of various growth factors. In the latter stage of clinical courses, proliferative potential and vascularity was seen to increase year by year. Expression of VEGF was upregulated and correlated with vascularity. On the other hand, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) were not overexpressed in this tumor. This case suggests that overexpression of VEGF and increased angiogenic potential might be involved in malignant transformation of meningiomas.

Adult

Origin and evolution of the Department of Neurosurgery, Neurological Institute, Faculty of Medicine, Kyushu University.

The Department of Neurosurgery at Kyushu University had its origins within the First Department of Surgery and was established as a subspecialty at the Neurological Institute more than 30 years ago under the leadership of Katsutoshi Kitamura. Further development of the neurosurgical department has proceeded during the chairmanship of Masashi Fukui. These leaders and many other dedicated physicians and surgeons, nurses, investigators from other countries, and staff members have contributed to the creation of a research-oriented neurosurgical environment that interacts fruitfully with the other components of the Neurological Institute. This article describes the development of neurosurgery within Kyushu, which has been a highly cosmopolitan area throughout its long history. More specifically, this account outlines the origin and growth of the Department of Neurosurgery at Kyushu University.

Faculty, Medical

Linkage of familial moyamoya disease (spontaneous occlusion of the circle of Willis) to chromosome 17q25.

BACKGROUND AND PURPOSE: Moyamoya disease is a cerebrovascular disease of unknown cause that mainly affects Japanese children. The incidence of familial occurrence accounts for 9% of cases. The characteristic lesions of moyamoya disease are occasionally seen in neurofibromatosis type 1, of which the causative gene (NF1) has been assigned to chromosome 17q11.2. METHODS: To determine whether a gene related to moyamoya disease is located on chromosome 17, we conducted microsatellite linkage analyses on 24 families containing 56 patients with moyamoya disease. Leukocyte DNA extracted from the family members was subjected to polymerase chain reaction for a total of 22 microsatellite markers on chromosome 17. The amplified polymerase chain reaction fragments were analyzed with GeneScan on an automated sequencer. RESULTS: Two-point linkage analysis gave a maximum log(10) odds (LOD) score of 3.11 at the recombination fraction of 0.00 for the marker at locus D17S939. The affected pedigree member method also showed a significantly low P value (<1. 0x10(-5)) for the 5 adjacent markers at 17q25. Multipoint linkage analysis also indicated that the disease gene is contained within the 9-cM region of D17S785 to D17S836, with a maximum LOD score of 4. 58. CONCLUSIONS: A gene for familial moyamoya disease is located on chromosome 17q25.

Cerebral Angiography

Linkage analysis of moyamoya disease on chromosome 6.

Genetic factors have been suggested to contribute to the etiology of moyamoya disease. The authors have previously reported an association between moyamoya disease and several alleles for human leukocyte antigens (HLA). To further specify the genetic component of moyamoya disease, a linkage study of moyamoya disease using markers on chromosome 6, where the HLA gene is located, was performed. The 15 microsatellite markers of chromosome 6 were studied in 20 affected sibling pairs. From an identical-by-descent analysis of these markers, an allele with possible linkage to moyamoya disease was identified. Sharing of the allele among affected members in 19 families was investigated, considering the haplotype. The marker, D6S441, might be linked to moyamoya disease. Considering the haplotype, the allele was shared among the affected members in 16 (82%) of the 19 families, but not in two others. In one family, sharing of the allele could not be determined because of low heterozygosity. Further studies are necessary to clarify multiple genetic factors that are definitely linked with moyamoya disease.

Alleles

Total syntheses of novel cytocidal beta-carboline alkaloids, oxopropalines D and G.

A new type of beta-carboline nucleus, N-methoxymethyl-4-methyl-beta-carboline (4) was synthesized by thermal electrocyclic reaction of a 1-azahexatriene system, involving the indole 2,3-bond. The key compound N-methoxymethyl-1-methoxycarbonyl-4-methyl-beta-carboline (2) was then prepared in a four-step sequence. The total synthesis of oxopropaline G (1e) was achieved from this key compound in four steps. Furthermore, the enantioselective total syntheses of (+)-oxopropaline D (1c) and its enantiomer were also achieved by application of the Sharpless oxidation-procedure in nine steps from 2.

Anti-Bacterial Agents

[Neuroimaging features of intraventricular neurocytoma].

We presented the clinicopathological features of 8 cases of intraventricular neurocytoma, which was a rare, benign tumor of neuronal origin and affected young patients. In each case the intraventricular tumor existed near the foramen of Monro and/or body of the lateral ventricle, and was associated with ventricular dilatation. A CT scan demonstrated a well-circumscribed iso- or hyperdense mass with some calcification, intratumoral cysts of various sizes and a heterogeneous enhancement. MRI, which was performed in 4 cases, confirmed a mass of isointense or slightly hyperintense on T 1-weighted images, and with multiple sites of attachment (mainly to the septum pellucidum and the head of the caudate nucleus). While these neuroimaging features are helpful in eliminating alternative diagnosis such as ependymomas, choroid plexus papillomas, subependymal giant cell astrocytomas and meningiomas, age of the patient and the tumor location within the lateral ventricle are important features for differential diagnosis.

Adult

cDNA cloning, expression and characterization of human prostaglandin F synthase.

A cDNA clone of prostaglandin F synthase (PGFS) was isolated from human lung by using cDNA of bovine lung-type PGFS as a probe and its protein expressed in Escherichia coli was purified to apparent homogeneity. The human PGFS catalyzed the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. The kcat/Km values for PGD2 and 9alpha,11beta-PGF2 were 21000 and 1800 min(-1) mM(-1), respectively, indicating that the catalytic efficiency for PGD2 and 9alpha,11beta-PGF2 was the highest among the various substrates, except for PQ. The PGFS activity in the cytosol of human lung was completely absorbed with antihuman PGFS antiserum. Moreover, mRNA of PGFS was expressed in peripheral blood lymphocytes and the expression in lymphocytes was markedly suppressed by the T cell mitogen concanavalin A. These results support the notion that human PGFS plays an important role in the pathogenesis of allergic diseases such as asthma.

Amino Acid Sequence

Solitary fibrous tumor in neurosurgical practice.

Solitary fibrous tumors most often affect the pleura, but examples are increasingly being reported in a wide variety of sites including the central nervous system. This tumor shows characteristic expression of CD34, which facilitates histopathologic differentiation of this lesion from other more common and better recognized spindle-cell tumors such as fibrous meningioma, hemangiopericytoma, or nerve sheath tumors. In this paper, we review current information on cranial and paracranial solitary fibrous tumors and emphasize the need for clinical recognition of this lesion as a distinct entity.

Journal Article