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N Sakai

Publications and source records attributed to N Sakai.

At least 199 records · Page 11Linked to original sources
PubMed1999

Activation of monocytes in vivo causes intracellular accumulation of lipoprotein-derived lipids and marked hypocholesterolemia--a possible pathogenesis of necrobiotic xanthogranuloma.

Necrobiotic xanthogranuloma (NXG) is a rare histiocytic disease with generalized xanthomatosis. However, most cases with NXG are normolipidemic or hypolipidemic. The mechanism for the formation of xanthoma in NXG has not yet been clarified. We observed a case of NXG with severe hypocholesterolemia (total cholesterol: 1.69 mmol/l) and analyzed the function of monocytes in this case. Histological examinations by light microscopy revealed a large amount of lipid deposition in the patient's freshly isolated monocytes. The patient's monocytes showed a 3-fold increase in cholesteryl ester content and a 3-fold enhancement of acetyl low density lipoprotein (LDL) uptake compared with the control monocytes. However, no significant difference was noted in the expression of CD36 protein and the mRNA levels of scavenger receptor-class A (SR-A) between the monocytes of the patient and the control. The phagocytotic ability of the patient's monocytes was enhanced 1.5-fold compared with that of the control monocytes. These findings suggest that the activated monocytes may have degraded the modified LDL via a pathway other than CD36 or SR-A, and accumulated a great amount of lipids in vivo. In conclusion, the present study has demonstrated a possible pathogenesis of NXG that the activation of monocytes in vivo may contribute to the intracellular accumulation of lipoprotein-derived lipids leading to non-inherited xanthomatosis and the marked hypocholesterolemia.

Aged↗
PubMed1999

Development of a dural arteriovenous fistula around the jugular valve after transvenous embolization of cavernous dural arteriovenous fistula.

BACKGROUND: Endovascular therapy for dural arteriovenous fistulas (DAVFs) is not without any risks, although it has been generally accepted to be a safe procedure. In this paper, we report a very rare complication: metachronous DAVF around a jugular valve 4 months after transvenous embolization. CASE DESCRIPTION: A 43-year-old woman presented with left proptosis, chemosis, and double vision. Cerebral angiography demonstrated a left cavernous DAVF. The patient's symptoms resolved almost completely after embolization with platinum coils via the superior ophthalmic vein. Four months later, angiography revealed a metachronous DAVF around a jugular valve. CONCLUSION: To our knowledge, only four such cases have been reported in the literature. Careful follow-up of patients treated with transvenous embolization and accumulation of such cases are needed to understand the pathogenesis of multiple DAVFs.

Adult↗
PubMed1999

The relationship between auditory ERP and neuropsychological assessments in schizophrenia.

To clarify the cognitive significance of event-related potential (ERP) abnormalities in schizophrenia, we examined the relationships of amplitudes and latencies of ERP components with performance on neuropsychological tests in schizophrenic patients. Twenty patients underwent the Trail Making B Test (TM-B), which is sensitive to frontal lobe dysfunction, and the logical memory, verbal paired-association, and visual reproduction subtests of the Wechsler Memory Scale (WMS), which are sensitive to temporal lobe dysfunctions, and ERP recordings during performance of an oddball auditory discrimination task. Pearson product-moment correlations indicated that an increased P200 amplitude was correlated with poor performance on the TM-B, whereas a decreased P300 amplitude was correlated with poor performance on the verbal paired-association subtest of the WMS. These findings suggest that a P200 abnormality represents the frontal lobe dysfunction, and a P300 abnormality represents the left temporal lobe dysfunction in schizophrenia.

Adolescent↗
PubMed1999

Possible routes of visceral information in the rat brain in formation of conditioned taste aversion.

When ingestion of a taste stimulus is paired with internal malaise, the animal remembers the taste and rejects its ingestion thereafter. This learning is referred to as conditioned taste aversion (CTA). To establish CTA in adult male Wistar rats, 0.1% saccharin and an i.p. injection of 0.15 M LiCl were used as the conditioned and unconditioned stimuli, respectively. Neuroanatomical study using the tracer method was performed to examine the ascending routes from the lateral part of the parabrachial nucleus (PBlat) which receives general visceral information and suggested the three possible routes to the amygdala: (1) direct route to the central nucleus of the amygdala (CeA); (2) diencephalic route to the basolateral nucleus of the amygdala (BLA) involving the zona incerta (ZI) and the midline and intralaminar thalamic complex (MITC); and (3) cortical route to the BLA involving insular cortex (IC). Rats with excitotoxic lesions of each of the CeA, ZI, MITC or IC had only a small or negligible effect on the acquisition of CTA. However, single lesions of the BLA and combined lesions of the ZI and IC, but not CeA and IC, almost completely abolished the acquisition of CTA. These results together with previous findings suggest that visceral (or unconditioned stimulus) information in the PBlat is sent to the BLA which is essential for the acquisition of CTA via the functionally important two parallel routes, the diencephalic and cortical routes, with either being able to create the aversion.

Amygdala↗
PubMed1999

Exacerbation of glomerulonephritis in subjects with chronic hepatitis C virus infection after interferon therapy.

We previously reported the glomerular deposition of hepatitis C virus (HCV) core antigen (Ag) in HCV-related nephropathy. In this study, we analyzed 23 HCV-positive subjects with exacerbation of proteinuria and/or hematuria during interferon (IFN) therapy and measured urinary protein selectivity. We also examined the involvement of HCV-related Ag using anti-HCV core (capside) Ag murine monoclonal antibody (Ab) and anti-core2 rabbit polyclonal Abs in nine subjects. Of 17 subjects, 13 (78%) showed low selective proteinuria. We found mesangial proliferative glomerulonephritis in 9 subjects, membranoproliferative glomerulonephritis in 1 subject, and nephrosclerosis in 1 subject. Immunofluorescence study showed the glomerular deposition of immunoglobulin G (IgG) or IgA and complements in all 9 subjects examined. Trace amounts only of HCV core Ag were detected along the glomerular capillary wall in 3 of 9 subjects (33%). Electron microscopy showed subendothelial or mesangial electron-dense deposits and also foot process effacement (20% to 72.5% of glomerular capillary walls) in all subjects and endothelial swelling in 4 subjects. In conclusion, IFN therapy for HCV may exacerbate the underlying glomerulopathies, unrelated to HCV Ags, through direct or indirect effects on glomerular endothelial and epithelial cells. Physicians should carefully distinguish HCV-related nephropathy from other glomerular diseases when they administer IFN therapy to HCV-positive subjects.

Adult↗
PubMed1999

Production of recombinant human type I procollagen homotrimer in the mammary gland of transgenic mice.

The large scale production of recombinant collagen for use in biomaterials requires an efficient expression system capable of processing a large (> 400 Kd) multisubunit protein requiring post-translational modifications. To investigate whether the mammary gland of transgenic animals fulfills these requirements, transgenic mice were generated containing the alpha S1-casein mammary gland-specific promoter operatively linked to 37 Kb of the human alpha 1(I) procollagen structural gene and 3' flanking region. The frequency of transgenic lines established was 12%. High levels of soluble triple helical homotrimeric [(alpha 1)3] type I procollagen were detected (up to 8 mg/ml) exclusively in the milk of six out of 9 lines of lactating transgenic mice. The transgene-derived human procollagen chains underwent efficient assembly into a triple helical structure. Although proline or lysine hydroxylation has never been described for any milk protein, procollagen was detected with these post-translational modifications. The procollagen was stable in milk; minimal degradation was observed. These results show that the mammary gland is capable of expressing a large procollagen gene construct, efficiently assembling the individual polypeptide chains into a stable triple helix, and secreting the intact molecule into the milk.

Amino Acids↗
PubMed1999

Attenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of prolonged administration of all-trans-retinoic acid (RA) on sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labelling and apoptotic indices and immunoreactivity of transforming growth factor (TGF) alpha in the gastric cancers was investigated in Wistar rats. After 25 weeks of carcinogen treatment, the rats were given chow pellets containing 10% sodium chloride and subcutaneous injections of RA at doses of 0.75 or 1.5 mg kg(-1) body weight every other day. In week 52, oral supplementation with sodium chloride significantly increased the incidence of gastric cancers compared with the untreated controls. Long-term administration of RA at both doses significantly reduced the incidence of gastric cancers, which was enhanced by oral administration of sodium chloride. RA at both doses significantly decreased the labelling index and TGF-alpha immunoreactivity of gastric cancers, which were enhanced by administration of sodium chloride, and significantly increased the apoptotic index of cancers, which was lowered by administration of sodium chloride. These findings suggest that RA attenuates gastric carcinogenesis, enhanced by sodium chloride, by increasing apoptosis, decreasing DNA synthesis, and reducing TGF-alpha expression in gastric cancers.

Adenocarcinoma↗
PubMed1999

A case of urethral recurrence found 15 years after radical cystectomy.

PURPOSE: A case of a urethral recurrence found 15 years after radical cystectomy is reported. METHODS/RESULTS: A 78-year-old man, who had undergone radical cystectomy at age 63, presented with urethral bleeding and positive cytology in urethral washing. The urethra was surgically resected. Pathologic examination revealed transitional cell carcinoma located in the distal and mid portion of the penile urethra. CONCLUSION: Evidence suggested that urethral recurrence resulted from the implantation from the primary bladder tumor; in addition, the urethral neoplasm had scarcely grown in the penile urethra for 15 years.

Cystectomy↗
PubMed1999

Inhibition of neutral sphingomyelinase activation and ceramide formation by glutathione in hypoxic PC12 cell death.

Reduced glutathione (GSH) and N-acetylcysteine (NAC), but not other antioxidative or reducing agents, were found to inhibit cell death, both apoptosis and necrosis, induced by hypoxia in naive and nerve growth factor-differentiated PC12 cells. The level of intracellular total GSH decreased time-dependently during hypoxia, but exogenously added GSH prevented such a decrease in GSH. Pretreatment of cells with exogenous GSH or NAC resulted in inhibition of both neutral sphingomyelinase (SMase) activation and ceramide formation during hypoxia. In the in vitro assay system, neutral SMase activity was inhibited dose-dependently by GSH and NAC. Activation of caspase-3 induced by hypoxia was also inhibited by either GSH or NAC. NAC but not GSH inhibited caspase-3 activation induced by C2-ceramide. These results suggest that GSH protects cells from hypoxic injury by direct inhibition of neutral SMase activity and ceramide formation, resulting in inhibition of caspase-3 activation, and that NAC exerts an additional inhibitory effect(s) downstream of ceramide.

Acetylcysteine↗
PubMed1999

MIP-1alpha and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis.

BACKGROUND: The precise molecular mechanisms of macrophage (Mphi) recruitment and activation in crescentic glomerulonephritis remain to be investigated. We hypothesized that locally produced macrophage inflammatory protein (MIP)-1alpha and monocyte chemoattractant protein (MCP)-1 via the chemokine receptors participate in the pathophysiology of human crescentic glomerulonephritis by recruiting and activating Mphi. METHODS: We investigated the levels of MIP-1alpha and MCP-1 by enzyme-linked immunosorbent assay (ELISA) in 20 healthy subjects, 20 patients with crescentic glomerulonephritis, and 41 control patients with various other renal diseases. The presence of MIP-1alpha, MCP-1, and the cognate chemokine receptor for MIP-1alpha, CCR5, in the diseased kidneys was evaluated by immunohistochemical and in situ hybridization analyses. RESULTS: MIP-1alpha-positive cells were mainly detected in crescentic lesions, whereas MCP-1 was mainly in the interstitium. In addition, we detected CCR5-positive cells in diseased glomeruli and interstitium. Urinary MIP-1alpha was detected in crescentic glomerulonephritis, even though it was below detectable levels in healthy subjects and in patients with other renal diseases without crescents. Urinary MIP-1alpha levels in the patients with crescentic glomerulonephritis were well correlated with the percentage of cellular crescents and the number of CD68-positive infiltrating cells and CCR5-positive cells in the glomeruli. However, urinary MCP-1 levels were well correlated with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Moreover, elevated urinary levels of both MIP-1alpha and MCP-1 dramatically decreased during glucocorticoid therapy-induced convalescence. CONCLUSIONS: These observations suggest that locally produced MIP-1alpha may be involved in the development of cellular crescents in the acute phase via CCR5 and that MCP-1 may be involved mainly in the development of interstitial lesions in the chronic phase when fibrocellular/fibrous crescents are present, possibly through Mphi recruitment and activation.

Adolescent↗
PubMed1999

Functional MR imaging with venography for neurosurgical identification of the central sulcus.

We evaluated the applicability of functional MR imaging overlaid onto brain images superimposed venography for neurosurgical identification of the central sulcus. In 20 volunteers and 12 patients with brain tumors located around the sensorimotor cortex, gradient echo and large flip angle functional MR image was performed to allow visualization of flow effect and susceptibility related changes in relative large vein by motor hand task. Functional MR image acquired was overlaid on 3D anatomical image with 3D venography. Based on the 3D mapping, intra-operative cortical somatosensory evoked potentials (SEPs) were recorded. The significant activation area obtained from functional MR imaging was projected on an ascending cortical vein in 16 volunteers (80%) and 10 patients (83%). Comparing the anatomical activation map with visual inspection of the exposed cortical surface made it easy to identify the activation area during surgery. The cortical veins in 9 of 10 were validated as a central vein by intra-operative cortical recording of SEPs. Combination of functional MR imaging overlaid onto 3D anatomical image with venography and intra-operative SEPs permitted rapid and accurate localization of the central sulcus during surgery.

Adult↗
PubMed1999

The characterization of human brain tumor using magnetization transfer technique in magnetic resonance imaging.

The clinical applicability of magnetization transfer (MT) technique in magnetic resonance imaging (MRI) for the estimation of the histological and constitutional feature of brain tumors was investigated. MT effect was evaluated by measuring the MT ratio (MTR). The parameters in 1.5-tesla MRI system were as follows: TR, 50 msec; TE, 5 msec; flip angle, 30 degree; offset frequency of off-resonance MT pulse, 1000 Hz. The sequence was performed in 20 normal volunteers and 45 patients with brain tumors which were characterized histologically and surgically. The MTR for brain tumors was significantly lower than that for normal brain tissue (p < 0.05). The MTR for meningioma was higher than that for the other brain tumors (p < 0.05). In the meningiomas, MTR for fibrous type was higher than that for meningothelial type, but there was no statistical significance. Regarding the physical consistency for the brain tumors, as classified by surgery, there was a statistically significant difference in MTR between the soft tumor group (0.22 +/- 0.03, n = 6) and the hard tumor group (0.36 +/- 0.04, n = 10) (p < 0.01). This study suggested that the MT technique for patients with brain tumor may be useful to understand the characteristics of the tumors presurgically, based on the degree of intermolecular interaction of macromolecule such as protein.

Adenoma↗
PubMed1999

Analysis of phospholipase C gene in patients with subarachnoid hemorrhage due to ruptured intracranial saccular aneurysm.

This study is designed to determine whether patients with aneurysmal subarachnoid hemorrhage have mutations in the phospholipase C-delta 1 (PLC-delta 1) gene, which was identified as a gene responsible for hypertension in spontaneously hypertensive rats. Seventy-two cases (31 male and 41 female) with intracranial saccular aneurysms were analyzed. The mean age was 60.1 +/- 11.5 years (mean +/- SD) (range 24-85 years). There were 35 patients (48.6%) with hypertension, 5 (6.9%) with diabetes mellitus, 12 (16.7%) with hyperlipidemia, 8 (11.1%) with ischemic heart disease, and 25 (34.7%) who were active smokers. The location of aneurysm was distributed as follows: 33 (33%) were at anterior cerebral artery, 23 (23%) were at middle cerebral artery, 28 (28%) were at internal carotid artery, and 16 (16%) were at vertebro-basilar artery. Six patients (8.3%) had a family history of intracranial aneurysms. There were 20 patients (27.8%) with multiple aneurysms, and 8 patients (11.1%) with a large or giant aneurysm. The four regions of PLC-delta 1 gene (bases 1099-1271, 1254-1401, 1343-1481, and 1882-2023) where genetic mutations were found in spontaneously hypertensive rats, were screened by PCR-SSCP analysis and their nucleotide sequences of all patients were determined. However, no mutations were detected in all patients. These results suggest that mutations of PLC-delta 1 gene previously implicated in hypertensive factor in rats may not be the case with human patients and therefore may be poorly related with aneurysmal subarachnoid hemorrhage.

Adult↗
PubMed1999

Intra-operative optical method using intrinsic signals for localization of sensorimotor area in patients with brain tumor.

The purpose of this study is intra-operatively to localize the sensorimotor area by intrinsic optical method detecting the changes in regional cerebral blood flow (rCBF) and cortical temperature following neuronal activity during median nerve stimulation. In 18 patients with brain tumors located around the sensorimotor cortex, cortical recording of somatosensory evoked potentials (SEPs) was performed and localized changes in rCBF during median nerve stimulation were measured by a laser-Doppler flowmeter on the locations of SEPs and around the activation area obtained by functional magnetic resonance imaging (fMRI). In two patients, cortical thermomapping was also performed during median nerve stimulation. In fMRI study, the significant activation area of sensorimotor could be obtained in 17 of 18 patients. In cortical recording of SEPs, the polarity reversal of N20 and P20 was observed in 14 of the 18 patients. In 9 of the 14 patients in whom SEPs could be recorded, the localized changes in rCBF, corresponding to the stimulation, were detected in the N20 area. In 2 of the 4 patients in whom N20 could not be recorded successfully, the localized changes in rCBF could be detected. The increase in rCBF during the stimulation was 18.3% +/- 5.3% (mean +/- SD, n = 11). Thermomapping could demonstrate the localized area, where the increase in rCBF was also detected, by observation of the changes in cortical temperature during the stimulation. The intra-operative intrinsic optical method detecting rCBF and cortical temperature in combination with recording of SEPs may be considered useful for brain functional localization related to neurosurgical disorders.

Aged↗
PubMed1999

Eotaxin contributes to renal interstitial eosinophilia.

BACKGROUND: A potent eosinophil chemotactic cytokine, human eotaxin, is directly chemotactic for eosinophils. Therefore, the specific expression of eotaxin in tissue might play a crucial role in tissue eosinophilia. However, the precise molecular mechanism of the recruitment and activation of eosinophils in human renal diseases remains to be investigated. We evaluated the role of eotaxin in the pathogenesis of human diffuse interstitial nephritis with marked infiltration of eosinophils. METHODS: In this study, we examined 20 healthy volunteers. 56 patients with primary or secondary glomerular diseases and two hypereosinophilic syndrome patients without renal involvement. Urinary and serum eotaxin levels were determined by an enzyme-linked immunosorbent assay. We also detected the presence of eotaxin protein immunohistochemically. RESULTS: On the one hand, urinary levels of eotaxin were significantly higher before the initiation of glucocorticoid administration in the patient with interstitial nephritis with marked infiltration of eosinophils. On the other hand, urinary eotaxin levels were not detected in any patients with nephrotic syndrome, interstitial nephritis without eosinophils, hypereosinophilic syndrome without renal involvement or other renal diseases. Serum eotaxin levels were not detected in any of the patients. Therefore, the detection of eotaxin in the urine was specific for renal interstitial eosinophilia. Moreover, endothelial cells, infiltrating mononuclear cells and renal epithelial cells in the tubulointerstitial lesions were immunostained with specific anti-eotaxin antibodies. Furthermore, the elevated urinary levels of eotaxin decreased dramatically during glucocorticoid-induced convalescence. HYPOTHESIS: We hypothesize that in situ expression of eotaxin may provide a new mechanism to explain the renal interstitial eosinophil infiltration.

Adolescent↗
PubMed1999

Absence of plasma protease-antiprotease imbalance in the formation of saccular cerebral aneurysms.

OBJECTIVE: We examined the hypothesis that a plasma protease-antiprotease imbalance contributes to the formation of saccular cerebral aneurysms and the suggestion that the assay of these enzymes might be a screening tool for people at higher risk for aneurysm formation. METHODS: From June 1997 through May 1998, the plasma leukocyte elastase, which is an important proteolytic enzyme, and alpha-antitrypsin and alpha2-macroglobulin, which are important antiproteolytic enzyme plasma proteins, were examined in 18 patients with ruptured aneurysms, 9 patients with unruptured aneurysms, and 22 controls. RESULTS: The elastase:alpha1-antitrypsin ratio and the elastase:alpha2-macroglobulin ratios were significantly higher in patients with ruptured aneurysms within 24 hours after subarachnoid hemorrhage (SAH) than in the controls. The protease-antiprotease imbalance depended on the elevation of the elastase level, which might be correlated with leukocytosis after SAH. The elastase level decreased to the control level 3 months after the onset of SAH. No significant difference in the elastase:alpha1-antitrypsin and elastase:alpha2-macroglobulin ratios was observed between the patients with unruptured aneurysms and the controls. CONCLUSION: These results do not support the hypothesis that a plasma protease-antiprotease imbalance is a potential marker to predict the formation of saccular cerebral aneurysms. The increase in plasma elastase levels in patients with ruptured aneurysms might be attributable to leukocytosis after SAH.

Adult↗
PubMed1999

Increase in apoptosis and decrease in ornithine decarboxylase activity of the gastric mucosa in patients with atrophic gastritis and gastric ulcer after successful eradication of Helicobacter pylori.

OBJECTIVE: Recent reports have shown that patients infected with Helicobacter pylori (H. pylori) have a higher risk of gastric cancer. However, the mechanism of this increased risk is still unclear. In the gastric mucosa, the size of a continuously renewed population of cells is determined by the rates of cell production and of cell loss. Ornithine decarboxylase (ODC) activity is elevated in various gastrointestinal cancers and serves as a marker of mucosal proliferative activity. Apoptosis occurs throughout the gut and is associated with cell loss. Both cell proliferation and cell loss have important roles in H. pylori-associated gastric carcinogenesis. Therefore, we investigated the effect of H. pylori eradication on ODC activity and apoptosis in the gastric mucosa of patients with atrophic gastritis and gastric ulcers. METHODS: Biopsy specimens of the gastric antrum were obtained at endoscopy from 17 H. pylori-positive gastric ulcers patients and 15 H. pylori-positive gastritis patients before and 4 wk after eradication therapy with amoxicillin, omeprazole, and a new anti-ulcer agent, ecabet sodium, and from 10 gastric ulcer patients in whom ulcer healed but H. pylori was left untreated. ODC activity and induction of apoptosis were determined immunohistochemically. RESULTS: H. pylori was successfully eradicated with the triple therapy in 12 (80%) of 15 gastritis patients and 13 (76%) of 17 gastric ulcer patients. ODC activity was present in the gastric mucosa in 21 (84%) patients before eradication but in only four (16%) patients after successful eradication (p = 0.0005). The apoptotic index increased significantly (p = 0.0006) from 4.2% +/- 0.4% before treatment to 7.4% +/- 0.5% after successful eradication. CONCLUSIONS: Successful eradication of H. pylori decreases mucosal ODC activity and increases apoptosis in the gastric mucosa. These findings indicate that by decreasing mucosal cell proliferation and increasing epithelial cell loss, H. pylori eradication may help decrease the subsequent risk of gastric cancer.

Adult↗