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Biomedical subjects

N Sakai

Publications and source records attributed to N Sakai.

At least 217 records · Page 12Linked to original sources
PubMed1999

Diagnosis of pancreatic cancer by detecting telomerase activity in pancreatic juice: comparison with K-ras mutations.

OBJECTIVE: Telomerase activity is reported to be specific and very frequent in human malignancy. K-ras mutations are also very frequently detected in pancreatic cancer, but their specificity for pancreatic cancer is controversial. We examined the telomerase activity and K-ras mutations in pancreatic juice from patients with pancreatic disease. METHODS: Pancreatic juice was obtained endoscopically at endoscopic retrograde pancreatography from 10 patients with pancreatic cancer, three with chronic pancreatitis, and three with a normal pancreas. The telomerase activity in pancreatic juice was assayed by telomeric repeat amplification protocol. K-ras mutations in exon 1 codon 12 were examined by the two-step polymerase chain reaction combined with restriction enzyme digestion, followed by single-strand conformation polymorphism analysis and direct sequencing. RESULTS: Telomerase activity of >5.0 was detected in eight of 10 (80%) subjects with pancreatic cancer, but in none with chronic pancreatitis or normal pancreas. K-ras mutations were detected not only in eight of 10 (80%) subjects with pancreatic cancer but also in two of three with chronic pancreatitis and in one of three with a normal pancreas. CONCLUSIONS: It was shown that the detection of telomerase activity in pancreatic juice is a more useful diagnostic tool for pancreatic cancer than that of K-ras mutations.

Aged↗
PubMed1999

Identification and functional analysis of novel cAMP response element binding protein splice variants lacking the basic/leucine zipper domain.

Two novel cAMP response element binding protein (CREB) splice variants were found by reverse transcription-polymerase chain reaction cloning by using mouse brain RNA as a template. One splice variant, named Delta-14, lacks 14 nucleotides at the beginning of exon 9 of the CREBDelta isoform. The other, named Delta-35, lacks 35 nucleotides at the beginning of exon 8 of CREBDelta. These nucleotide deletions cause frame shifts for codon usage, producing proteins which conserve the major phosphorylation site (Ser(133)) but lack the basic/leucine zipper domain, which is essential for binding to DNA and to other transcription factors. Both variants are widely expressed in peripheral tissues, but are enriched in brain, thymus, and testis. CREBDelta-14 and Delta-35 variant proteins were expressed by using an in vitro translation system and by transfecting into human embryonic kidney 293 cells. Both variants were detected by a CREB antibody that recognizes the CREBDelta amino terminus, but not by an antibody which recognizes the CREBDelta carboxy terminus, as would be predicted based on the frame shift. Activation of the cAMP pathway increased phospho-CREB immunoreactivity, indicating that these variants are substrates of cAMP-dependent protein kinase. In addition, immunocytochemical analysis demonstrated that CREBDelta-14 and Delta-35 are primarily cytosolic, whereas CREBalpha is predominantly in the nucleus. Finally, expression of CREBDelta-14 or Delta-35 decreased cAMP responsive element-chloramphenicol acetyltransferase reporter activity, demonstrating that both can function as repressors of endogenous CREB.

Alternative Splicing↗
PubMed1999

Pax1 and Pax9 synergistically regulate vertebral column development.

The paralogous genes Pax1 and Pax9 constitute one group within the vertebrate Pax gene family. They encode closely related transcription factors and are expressed in similar patterns during mouse embryogenesis, suggesting that Pax1 and Pax9 act in similar developmental pathways. We have recently shown that mice homozygous for a defined Pax1 null allele exhibit morphological abnormalities of the axial skeleton, which is not affected in homozygous Pax9 mutants. To investigate a potential interaction of the two genes, we analysed Pax1/Pax9 double mutant mice. These mutants completely lack the medial derivatives of the sclerotomes, the vertebral bodies, intervertebral discs and the proximal parts of the ribs. This phenotype is much more severe than that of Pax1 single homozygous mutants. In contrast, the neural arches, which are derived from the lateral regions of the sclerotomes, are formed. The analysis of Pax9 expression in compound mutants indicates that both spatial expansion and upregulation of Pax9 expression account for its compensatory function during sclerotome development in the absence of Pax1. In Pax1/Pax9 double homozygous mutants, formation and anteroposterior polarity of sclerotomes, as well as induction of a chondrocyte-specific cell lineage, appear normal. However, instead of a segmental arrangement of vertebrae and intervertebral disc anlagen, a loose mesenchyme surrounding the notochord is formed. The gradual loss of Sox9 and Collagen II expression in this mesenchyme indicates that the sclerotomes are prevented from undergoing chondrogenesis. The first detectable defect is a low rate of cell proliferation in the ventromedial regions of the sclerotomes after sclerotome formation but before mesenchymal condensation normally occurs. At later stages, an increased number of cells undergoing apoptosis further reduces the area normally forming vertebrae and intervertebral discs. Our results reveal functional redundancy between Pax1 and Pax9 during vertebral column development and identify an early role of Pax1 and Pax9 in the control of cell proliferation during early sclerotome development. In addition, our data indicate that the development of medial and lateral elements of vertebrae is regulated by distinct genetic pathways.

Animals↗
PubMed1999

Transport and recognition of aminopeptidase-resistant cellobiose-coupled tyrosylglycylglycine by intestinal Na+/glucose cotransporter (SGLT1): recognition of sugar conjugates by SGLT1 is much less restricted than transport.

Transport and recognition of aminopeptidase-resistant cellobiose-coupled tyrosylglycylglycine (CcpTGG) by intestinal Na+/glucose cotransporter (SGLT1) was examined in rat small intestine. Inhibitory effect of phloridzin (SGLT1 inhibitor) on the CcpTGG transport was extremely low. Concentration dependence of the CcpTGG transport was observed, but the primary component of transport was passive diffusion. However, CcpTGG significantly inhibited SGLT1-mediated transport, indicating its recognition by SGLT1. Other glucose-conjugates also inhibited SGLT1-mediated transport. These results indicate that recognition of sugar conjugates by SGLT1 is much less restricted than transport, and that it should be relatively easier to design SGLT1 inhibitors than SGLT1-transportable sugar conjugates.

Aminopeptidases↗
PubMed1999

Angiographically occult dural arteriovenous malformation in the anterior cranial fossa--case report.

A 62-year-old male presented with a dural arteriovenous malformation located in anterior cranial fossa manifesting as acute right frontal intracerebral and subdural hematomas. Cerebral angiography showed only mass sign, but surgical exploration disclosed the dural arteriovenous malformation in the anterior cranial fossa. Anterior cranial fossa dural arteriovenous malformation should be considered if computed tomography reveals intracranial bleeding involving the frontal base, even if cerebral angiography does not demonstrate vascular anomalies.

Cerebral Angiography↗
PubMed1999

Primary intracranial squamous cell carcinoma--case report.

A 50-year-old female presented with primary intracranial squamous cell carcinoma (SCC) at the right cerebellopontine angle manifesting as right facial nerve paresis. She had undergone gross total removal of a right cerebellopontine angle epidermoid cyst 10 years before and had done well until recently. Magnetic resonance imaging showed a heterogeneous tumor with markedly enhanced irregular margin. Subtotal removal of the tumor was achieved. Histological examination showed moderately differentiated SCC. After surgery, she underwent chemotherapy and gamma radiosurgery. She is now well 5 years after the diagnosis of SCC.

Adult↗
PubMed1999

Permissible arterial occlusion time in aneurysm surgery: postoperative hyperperfusion caused by temporary clipping.

The relationship between hyperperfusion and temporary clipping was evaluated to determine the safe limit for the duration of temporary clipping in aneurysm surgery. Twenty-one patients surgically treated for a ruptured aneurysm were examined using xenon-enhanced computed tomography on postoperative days 4 to 13. Eight of the 16 patients undergoing temporary clipping had focal hyperperfusion; whereas the five patients without temporary clipping had no hyperperfusion. Mean total temporary clipping time in patients with hyperperfusion was significantly longer than that in patients without (31.9 vs. 13.9 minutes, p = 0.0157) and mean maximum single temporary clipping time in patients with hyperperfusion was also significantly longer than in patients without (18.4 vs. 8.6 minutes, p = 0.0313). Moreover, cerebral infarction was related to hyperperfusion (p = 0.0027). These results support the hypothesis that temporary clipping during aneurysm surgery causes postoperative hyperperfusion and cerebral infarction. Temporary clipping may be harmful when performed for more than 20 minutes of total duration, since postoperative hyperperfusion was seen under this condition.

Adult↗
PubMed1999

Skull metastasis of Ewing's sarcoma--three case reports.

Three cases of skull metastasis of Ewing's sarcoma were treated. The metastatic lesion was located at the midline of the skull above the superior sagittal sinus in all cases. Surgery was performed in two patients with solitary skull lesions involving short segments of the superior sagittal sinus without remarkable systemic metastasis, resulting in good outcome. The third patient had extensive, multiple tumors involving the superior sagittal sinus which could not be excised, and died due to intracranial hypertension. The surgical indication for skull metastasis of Ewing's sarcoma depends on the location and length of the involved superior sagittal sinus, and general condition.

Adolescent↗
PubMed1999

Polymorphism of the endoglin gene in patients with intracranial saccular aneurysms.

OBJECT: Endoglin, a transforming growth factor beta-binding protein, is a glycoprotein expressed on the surface of human vascular endothelial cells. Mutations of this gene are responsible for hereditary hemorrhagic telangiectasis and are associated with sporadic intracerebral hemorrhage as a risk factor. The purpose of this study was to examine the polymorphism of this gene in patients with intracranial aneurysms. METHODS: The authors identified the mutations and insertion polymorphism around exon 7 of the endoglin gene in 82 patients with intracranial saccular aneurysms (aneurysm group) and 114 control volunteers (control group). A 6-base insertion (GGGGGA) was found in intron 7 at 26 bases beyond the 3' end of exon 7. The homozygous insertion of intron 7 of the gene was present in 20.7% of the aneurysm group compared with 6.1% of the control group (chi2 = 9.837, p = 0.0073). The insertion allele frequency was significantly higher in the aneurysm group (67 [40.8%] of 164) than that in the control group (63 [27.6%] of 228) (chi2 = 7.48, p = 0.0062). The most notable clinical characteristic of the 17 patients with homozygous insertion in the aneurysm group was the relatively high percentage of patients with hypertension and of those with multiple aneurysms. CONCLUSIONS: The data provide evidence of an association between aneurysm development and a polymorphism at a genetic variant of endoglin in patients with these lesions.

Adult↗
PubMed1999

A novel fungal metabolite NG-061 enhances and mimics neurotrophic effect of nerve growth factor (NGF) on neurite outgrowth in PC12 cells.

During the course of our screening program for low molecular natural products with their ability to potentiate and/or mimic neurotrophic effect of NGF, a novel fungal metabolite, phenylacetic acid hydrazide derivative NG-061 was isolated from the fermentation broth of Penicillium minioluteum F-4627. NG-061 enhanced and mimicked neurotrophic effect of NGF on neurite outgrowth in a rat pheochromocytoma cell line PC12.

Animals↗
PubMed1999

[Two cases of interstitial cystitis complicated with migraine].

Two cases of interstitial cystitis complicated with migraine and atopic tendency are reported. In the bladder tissue of the two cases, mast cells were increased and in one case which was observed with immunohistochemical staining, most of the mast cells among muscle layers were chymase-positive mast cells. We considered that the degranulation of mast cells was related with the cause of interstitial cystitis and migraine.

Aged↗
PubMed1999

[Detection of anti-IgA alloantibody in a case of non-hemolytic transfusion reaction].

A 59-year-old man with myelodysplastic syndrome exhibited unticaria, dyspnea, fever, and hypotension immediately after the start of platelet concentrate (PC) transfusion on the 15th day of hospitalization. On the 17th and 21st day of hospitalization, the patient exhibited severe unticaria resembling that of erythroderma after the start of PC transfusion. Anti-IgA IgG antibody was detected by enzyme-linked immunosorbent assay (ELISA) on the 28th day of hospitalization. Anti-IgA (purified from pooled human plasma) was detected by Western blotting. The patient's IgA level was normal. No antibodies against HLA or platelet-specific antigens were detected in serum. The patient had no reaction to administration of washed PC. These findings suggest that anti-IgA antibody might have been responsible for the nonhemolytic transfusion reaction in this patient.

Antibodies, Anti-Idiotypic↗
PubMed1999

Photophysical studies of A2-E, putative precursor of lipofuscin, in human retinal pigment epithelial cells.

With age, human retinal pigment epithelial cells accumulate lipofuscin that can absorb photons in the visible range leading to light-induced damage and impaired vision. A putative precursor of lipofuscin, 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E, 5E,7E- octatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6-(2,6,6-trimethyl-1 - cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2-E), has recently been isolated and characterized from aged human retinal pigment epithelial cells. We have found that A2-E inhibits the growth of human retinal pigment epithelial cells at concentrations greater than 1 microM. Time-resolved fluorescence measurements of 1 microM A2-E in solution, performed under 413 nm excitation, showed that fluorescence wave forms integrated across the spectrum (450-600 nm) were best-fitted with three decay times in the nanosecond and subnanosecond time scale: 6.6, 1.9 and 0.33 ns. Untreated retinal pigment epithelial cells were characterized by three fluorescence lifetimes: 6.3, 1.7 and 0.35 ns. In retinal pigment epithelial cells treated with 1 microM A2-E, the fluorescence decay was significantly faster, with the marked presence (approximately equal to 30%) of a fourth short lifetime (0.12 ns). These fluorescence decay times for A2-E bound to human retinal pigment epithelial cells are similar to those of lipofuscin granules isolated from aged human retinal pigment epithelial cells. This similarity supports the hypothesis that A2-E is a precursor of lipofuscin and suggests that A2-E may play a role in the overall light damage associated with age-related retinal diseases.

Aging↗
PubMed1999

[Endovascular surgery for untreated ruptured aneurysm with symptomatic vasospasm].

It is difficult to treat ruptured aneurysms with symptomatic vasospasm. Although direct surgery for such cases is associated with poor outcomes, conservative therapy has the risk of both rerupture and infarction. In two cases of ruptured aneurysms with symptomatic vasospasm, we performed aneurysmal coil embolization with Guglielmi electrodetatchable coils (GDC). At the same time we performed percutaneous transluminal angioplasty (PTA) with papaverine infusion. In both cases, rerupture did not occur and PTA was effective angiographically. A good outcome was achieved in case 1. However, broad cerebral infarction occurred in case 2, in which the patient had shown severe symptomatic vasospasm on admission. In advanced cases, such as in case 2, the outcome is poor. The aneurysm may not be able to be approached before PTA because of severe vasospasm. In such cases, PTA must be performed carefully to avoid aneurysmal rerupture. Intraarterial papaverine infusion is safer than PTA for severe spasm in distal vessels. However the efficacy of papaverine is known to be transient in many cases. It is often difficult to determine the exact relationship between branches and the aneurysm in the presence of vasospasm. In such cases, we recommend that the rupture point be packed and that the aneurysmal neck remain unpacked. After vasospasm is cured and good general condition has been recovered, direct surgery can be performed. In summary, endovascular surgery is an effective option for treatment of ruptured aneurysm with symptomatic vasospasm.

Aged↗
PubMed1999

[The role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein (MCP)-1 in subgroups of rapidly progressive glomerulonephritis].

To elucidate the role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein(MCP)-1 in the pathogenesis of rapidly progressive glomerulonephritis (RPGN), we determined the urinary levels of MCAF/MCP-1 in 20 healthy subjects, 30 patients showing RPGN with crescents, and 39 patients with various types of renal diseases without crescents. We divided RPGN into two subgroups, the acute type and the insidious type, with regard to the declination rate of reciprocals of serum creatinine with time as previously reported. In addition, we divided the patients with RPGN into anti-neutrophil cytoplasmic antibody(ANCA)-related diseases and immune complex(IC)-mediated diseases with regard to etiology. Urinary levels of MCAF/MCP-1 were significantly higher in patients with RPGN as compared with those of other renal diseases and healthy volunteers(21.8 +/- 4.5 vs. 11.6 +/- 3.5, 1.0 +/- 0.1 pg/ml creatinine, respectively, p < 0.01, mean +/- SEM). There was no difference in the urinary levels of MCAF/MCP-1 between the acute and insidious types of RPGN patients. In addition, there was no difference in the urinary levels of MCAF/MCP-1 between the patients with ANCA-related and IC-mediated diseases. Urinary levels of MCAF/MCP-1 in patients with RPGN were correlated well with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Immunohistochemical examinations revealed that MCAF/MCP-1 positive cells were detected in tubular epithelial and endothelial cells and mononuclear infiltrated cells in the interstitium. Moreover, elevated urinary MCAF/MCP-1 levels in patients with RPGN, regardless of subgroups, were dramatically decreased during methylprednisolone pulse therapy induced convalescence. These results suggest that MCAF/MCP-1 may be involved in the pathogenesis of RPGN via macrophage recruitment and activation.

Anti-Inflammatory Agents↗
PubMed1999

Effects of tinnitus on posture: a study of electrical tinnitus suppression.

We investigated the effects of tinnitus on postural responses using posturography. Thirty-three tinnitus patients (19 female and 14 male) ranging in age from 33 to 67 years (mean age, 53) were selected randomly at our outpatient clinic. Nobody complained of dizziness. Posturographic examination was given before and after 30-minute electrical stimulation. Items tested were envelope area, area (root mean square), total length, total length-area, mean amplitude of lateral body sway (mx), and anteroposterior sway (my). Those parameters did not improve in patients without tinnitus relief. Two postural measures (envelope area and mx) showed significant improvement in patients with tinnitus relief. These effects appeared only on positions involving restricted visual feedback. In a comparison of postural measures in patients with and without tinnitus relief, all parameters except total length and mx improved significantly in patients with eyes open. Our study showed that aside from the auditory system, tinnitus can affect balance, implying that tinnitus may be a factor in increasing unsteadiness in patients with tinnitus.

Adult↗
PubMed1999

Effects of greater occipital nerve block on tinnitus and dizziness.

We analyzed relationships among tinnitus relief, dizziness, and results of vertical autocorrelation studies of head movement to investigate the effect of greater occipital nerve block on the sensory and motor system in 2 patients with abnormal head movement. Tinnitus improved in 14 (52%) of 28 tinnitus patients after occipital nerve block. The percentage of patients reporting tinnitus improvement (54%, or 7 patients) among 13 patients without a history of trauma was not significantly higher than among 12 patients with trauma (33% or 4 patients). However, tinnitus improvement in patients with dizziness but without trauma was more frequent than that reported by nontraumatic tinnitus patients without dizziness (p<.05). Vertical autocorrelation results while stepping in place were better in patients with tinnitus relief than in those not reporting tinnitus relief (p =.001). Dizziness improved in 8 of 13 patients (62%) with trauma, similar to improvement in 8 of 14 patients without trauma (57%). Improved word perception test results in the presence of noise suggested that improvement in tinnitus and dizziness after occipital nerve block was related to improved attention.

Adult↗