Biomedical subjects

N Sakai

Publications and source records attributed to N Sakai.

At least 253 records · Page 14Linked to original sources

PubMed1998

Role of the medial and lateral parabrachial nucleus in acquisition and retention of conditioned taste aversion in rats.

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. To elucidate the functional role of the medial part of the parabrachial nucleus (PBmed) which receives taste information and the lateral part (PBlat) which receives general visceral information, confined electrolytic lesions were made to either of these regions. Rats with bilateral lesions of the PBlat impaired the acquisition of CTA, but those lesions made after the acquisition of CTA had no effect on the retention of this learning. The bilateral lesions of the PBmed abolished the acquisition and retention of CTA. The PBlat-lesioned rats showed normal taste preference behavior, but PBmed-lesioned rats showed impaired sensibility to taste stimuli. These results suggest that both the PBlat and PBmed are essential for the acquisition of taste aversion learning, but the PBlat is not necessary for retrieval of CTA.

Animals↗

PubMed1998

The significance of the expression of tumor suppressor gene DCC in human gliomas.

Deleted in colorectal carcinoma (DCC) gene has been as a candidate of tumor suppressor genes, has been identified recently and is thought to relate to the metastatic potential in some cancers. We examined the gene in 60 human gliomas (26 glioblastomas multiforme (GBMs), 16 anaplastic astrocytomas (AAs), 6 low grade astrocytomas (LGAs) of WHO Grade II, and 11 recurrent gliomas) and A172 human GBM cell line by reverse transcription polymerase chain reaction (RT-PCR). Twenty (77%) GBMs, 11 (69%) AAs, and 1 (17%) LGA revealed the reduced or absent DCC expression. Reduced DCC expression was also shown in 10 (91%) recurrent gliomas. Furthermore, in 5 cases with both primary and recurrent GBM, the DCC expressions of all recurrent tumors were lower than those of primary tumors. No significant correlation between DCC expression and Mib-1 labeling index was confirmed. The survival rate of patients without reduced DCC expression was significantly superior to that of patients with reduced DCC expression in overall malignant astrocytic tumors. In GBM and AA separately, DCC expression also tended to correlate with patient's prognosis. These results suggest that reduced DCC expression is an important marker in tumor malignancy and recurrence in astrocytic tumors and that may be a useful prognostic factor in patients with malignant astrocytic tumors.

Adolescent↗

PubMed1998

Species differences of serum albumins: III. Analysis of structural characteristics and ligand binding properties during N-B transitions.

PURPOSE: The aim of this study was to investigate the characteristics of the structural transitions and changes in ligand binding properties of different albumins during the pH-dependent structural transition, often referred to as the N-B transition. METHODS: Structural transitions were evaluated by means of spectrometry, differential scanning calorimetry and chemical modification. In addition, ligand binding properties were investigated using typical site-specific bound drugs (warfarin, phenylbutazone, ibuprofen and diazepam). RESULTS: Conformational changes, including N-B transition, clearly occurred in albumins from all species used in this study. The conformational stabilities of all the albumins were clearly lost in the weakly alkaline pH range. This was probably the result of the destruction of salt bridges between domain I and domain III in the albumin molecule. In addition, the profiles of the ANS-induced fluorescence were different and could be classified into two patterns, suggesting that hydrophobic pockets in the albumin molecules were different for the different species. The data suggest that the amino acid residues responsible for the transitions were some of the His residues located in domain I. Further, the ligand binding properties of the albumins were slightly different but statistically significant. CONCLUSIONS: The overall mechanisms of the N-B transition may be similar for all the albumins, but its impact is considerably different among the species in terms of both structural characteristics and ligand binding properties. Furthermore, the transitions appear to be multi-step transitions.

Animals↗

PubMed1998

Low prevalence of Helicobacter pylori infection in patients with hamartomatous fundic polyps.

Helicobacter pylori infection of the gastric mucosal surface was investigated in patients with hamartomatous fundic polyps or hyperplastic polyps and in patients without endoscopic evidence of disease (healthy subjects). Presence of H. pylori infection was determined by culture, histologic examination, and the endoscopic phenol red test. Adherence of H. pylori was evaluated with scanning electron microscopic examination of antral biopsy specimens. Both prevalence of H. pylori infection (P < 0.001) and H. pylori adherence (P < 0.05) were less in patients with hamartomatous fundic polyps than in healthy subjects and patients with hyperplastic polyps. However, the percentages of plasma cells in gastric mucosa that contained IgA and of gastric epithelial cells that expressed Lewis b did not differ significantly among the three groups. These findings suggest that defense mechanisms against the attachment of H. pylori other than IgA or Lewis b antigen are present in patients with hamartomarous fundic polyps.

Biopsy↗

PubMed1998

Inhibition by transforming growth factor (34-43)-alpha, a TGF-alpha antagonist, of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of prolonged administration of transforming growth factor (34-43)-alpha, an antagonist of TGF-alpha, on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the labelling and apoptotic indices and TGF-alpha immunoreactivity of gastric mucosa and gastric cancers was examined in Wistar rats. The rats received intraperitoneal injections of 10 or 20 microg kg(-1) body weight of TGF(34-43)-alpha every other day after oral treatment with MNNG for 25 weeks. Long-term administration of TGF(34-43)-alpha at both doses significantly reduced the incidence of gastric cancers at the end of the experiment in week 52. However, TGF(34-43)-alpha had no significant effect on the number, histological type or depth of involvement of gastric cancers. Administration of TGF(34-43)-alpha also significantly decreased the bromodeoxyuridine labelling index and TGF-alpha immunoreactivity, and significantly increased the apoptotic index of antral mucosa and gastric cancers. These findings indicate that TGF(34-43)-alpha inhibits gastric carcinogenesis, and that its effects are mediated through decreased cell proliferation and TGF-alpha immunoreactivity and increased apoptosis induction in the gastric cancers.

Adenocarcinoma↗

PubMed1998

Expansion of the oral end of free revascularised jejunum with a jejunal patch flap rotated like a folding fan.

We have devised a new expansion process for the reconstruction of the cervical oesophagus with free revascularised jejunum in cases of hypopharyngeal cancer. The jejunal island flap is divided into three subislands and the major island of the caudal end is split partially at its oral end. The middle island is split, trimmed triangularly, and inserted into opened major island to expand the diameter of the oral end of the conduit for the cervical oesophagus and to make it funnel-shaped. The smallest island on the oral side is used as a circulation monitor for the transferred jejunum. Because the jejunal island patch is rotated around the root of mesentery like a folding fan and joined to the major island, there is neither shortening of the pedicle nor distortion. This method allows expansion of the oral end by up to 180% to facilitate end to end anastomosis in proximal pharyngeal defects.

Aged↗

PubMed1998

Clinical applicability of functional magnetic resonance imaging and activation study with single photon emission computerized tomography for functional mapping.

The purpose of this study is to estimate the clinical applicability of functional magnetic resonance imaging (f-MRI) combined with the activation study using single photon emission computerized tomography (SPECT) with special reference to identification of primary sensorimotor area. Five healthy volunteers and 5 patients with brain tumors located around the sensorimotor cortex were studied by both f-MRI with gradient echo and SPECT with 99mTc-ethyl cysteinate dimer using split-dose and subtraction method. In f-MRI study, the significant activation of the sensorimotor area was observed in all subjects. Various concurrent activation regions such as supplementary motor (2 volunteers vs. 4 patients), premotor (1 vs. 2) and ipsilateral sensorimotor area (1 vs. 2) were also observed. In the cases with the activation of neighboring regions of sensorimotor area, it was difficult to identify the area in f-MRI. In SPECT study, the sensorimotor area was depicted as the most increased area in regional cerebral blood flow in eight cases, the characteristics of which were helpful to diagnose the area, while significant activation of the area with edema could not be detected in two patients. Consequently, the sensorimotor area was cross-validated with both the modalities. This study demonstrated that it would be valuable to use both techniques for the clinical assessment of the sensorimotor area.

Adult↗

PubMed1998

Pulsed off-resonance magnetization transfer for brain tumor in patients.

We investigated the clinical applicability of pulsed off-resonance magnetization transfer (MT) technique in magnetic resonance (MR) imaging for the estimation of the histological feature of brain tumor. The parameters were optimized using bovine serum albumin (BSA) solutions and gels in 1.5-tesla MR system as follows: TR, 50 msec; TE, 5 msec; flip angle, 30 degree; offset frequency, 1000 Hz. MT effect was evaluated by measuring the MT ratio (MTR) and reconstructing calculated MTR color image. The MTRs of the BSA solutions and gels increased with increasing concentrations of protein, while the MTRs of the gels were remarkably higher than those of the solutions. The optimized sequence was performed in 20 healthy volunteers and 30 patients with brain tumors. In normal brains, the MTRs were significantly higher in white matter than in gray matter (p < 0.05). The MTR in brain tumor was significantly lower than that in normal brain tissue (p < 0.05) and the calculated MTR image produced contrast between brain tumor and normal brain tissue. There was a statistically significant difference in MTR between benign (0.30 +/- 0.05, n = 17) and malignant (0.26 +/- 0.04, n = 13) tumors (p < 0.05). The optimized MT technique is quite sensitive for estimating the degree of intermolecular interaction between macromolecules and water within the central nervous system.

Brain Neoplasms↗

PubMed1998

Angiotensin I-converting enzyme gene polymorphism in intracranial saccular aneurysm individuals.

A polymorphism in the angiotensin I-converting enzyme (ACE) gene has been associated with cerebrovascular diseases as a new potent risk factor. The purpose of this study was to investigate an association of the gene polymorphism with intracranial saccural aneurysmal patients. The study population consisted of 83 aneurysmal patients (age range 41-85 years) (the AN group) and 104 matched control subjects (age range 30-81 years) (the Control group). For detection of the ACE gene polymorphism, the standard PCR method was performed by using genomic DNA isolated from peripheral blood leukocytes. The PCR products were a 490-bp in the presence of the insertion (I) and a 190-bp fragment in the absence of the insertion (D). The ACE gene polymorphism was classified into three genotypes: I/I genotype (a 490-bp band); D/D genotype (a 190-bp band); or I/D genotype (both a 490-bp and a 190-bp band). The number of subjects with I/I, I/D, and D/D genotypes was 38, 40, and 5 in the AN group and 43, 45, and 16 in the Control group, respectively. The frequency of the D/D genotype in the AN group was significantly lower (5/83 = 0.06) than that in the Control group (16/104 = 0.15) (chi 2 = 4.06; p = 0.044). There was no significant difference between the genotype sof hypertensive patients and normotensive patients in the AN group. Thus, this present study suggests that genetic heterogeneity of the ACE gene may be correlated with the etiology of intracranial aneurysms.

Adult↗

PubMed1998

Prognostic factors in supratentorial WHO grade II astrocytoma in adults.

The records of 33 adult patients with supratentorial World Health Organization grade II astrocytoma (A-II) treated between January 1980 and April 1997 at our hospitals were retrospectively reviewed. All tumours were surgically resected or biopsied and their MIB-1 labelling indices (LIs) were less than 1.5%. The median time to tumour progression after the initial surgery was 60 months, and the 5- and 10-year tumour progression-free rates were 53 and 39%, respectively. The median survival time was 107 months, and the 5- and 10-year survival rates were 66 and 43%, respectively. The major cause of death was tumour recurrence with malignant transformation, comprising 93% of all deaths due to unrestrained tumour growth. In a univariate analysis for survival rate by log-rank test, age (< 60 years), Karnofsky Performance Scale score (90-100%), tumour location (except for the basal ganglia), and extent of surgery (more than biopsy) were revealed to be significant positive prognostic factors. A Cox proportional hazard multivariate regression analysis confirmed that the age was the only independent, significant positive prognostic factor in this series. The survival time after the initial surgery in patients without radiotherapy tended to be prolonged compared with those of the patients with radiotherapy. Of the 26 patients who received radiotherapy, however, the survival time after the initial surgery in the nine patients with intraoperative radiotherapy was significantly prolonged compared with the 17 patients who received sole external beam radiotherapy. Gender, symptoms, histology, p53 LI, enhancement on CT/MRI, cyst, calcification and chemotherapy were not shown to be significant prognostic factors. The optimal management strategy for A-II is expected to be established by clarification of the natural history with cytological and molecular biological analyses of the biological features of this disease.

Adult↗

PubMed1998

Comparison of different computed tomography scanning methods for quantifying emphysema.

Computed tomography (CT) is used to detect emphysematous changes in the lungs of living patients. It is therefore important to develop a standard method for the radiographic quantification of emphysematous lesions using CT. The authors determine the best CT scanning methods for assessing the degree of pulmonary emphysema. Computed tomography scanning was performed in 85 consecutive patients with stable chronic obstructive pulmonary disease. Scans were obtained using 2-mm or 5-mm collimation, at full inspiration or full expiration, and with standard or high spatial-resolution reconstruction images (eight images each). Emphysema was then assessed by visual scoring using a five-point scale for each lung. Emphysema was scored as significantly less severe using standard reconstruction images. There were no significant differences in CT-scored emphysema on scans obtained with 2-mm and 5-mm collimation. Emphysema was scored as significantly less severe on expiratory scans. The postbronchodilator forced expiratory volume in one second value correlated better with emphysema scored on expiratory scans. Computed tomography-scored emphysema obtained by all methods correlated well with the diffusion capacity and total lung capacity, regardless of the method used. Using a visual scoring system with a five-point scale, narrow collimation is probably not necessary for the quantification of emphysema, although a high spatial-resolution reconstruction appears to be of value. Scans obtained in exhalation appear to underemphasize the severity of emphysema.

Aged↗

PubMed1998

Transgenic animals with inducible, targeted gene expression in brain.

Several inducible gene expression systems have been developed in vitro in recent years to overcome limitations with traditional transgenic mice. One of these, the tetracycline-regulated system, has been used successfully in vivo. Nevertheless, concerns remain about the ability of this system to direct high levels of transgene expression in vivo and to enable such expression to be turned on and off effectively. We report here the generation, using a modified tetracycline-regulated system under the control of the neuron-specific enolase promoter, of several lines of mice that direct transgene expression to specific brain regions, including the striatum, cerebellum, CA1 region of the hippocampus, or deep layers of cerebral neocortex. Transgene expression in these mice can be turned off completely with low doses of doxycycline (a tetracycline derivative) and driven to very high levels in the absence of doxycycline. We demonstrate this tissue-specific, inducible expression for three transgenes: those that encode luciferase (a reporter protein) or DeltaFosB or the cAMP-response element binding protein (CREB) (two transcription factors). The various lines of transgenic mice demonstrate an inducible system that generates high levels of transgene expression in specific brain regions and represent novel and powerful tools with which to study the functioning of these (or potentially any other) genes in the brain.

Animals↗

PubMed1998

Three distinct mechanisms for translocation and activation of the delta subspecies of protein kinase C.

We expressed delta subspecies of protein kinase C (delta-PKC) fused with green fluorescent protein (GFP) in CHO-K1 cells and observed the movement of this fusion protein in living cells after three different stimulations. The delta-PKC-GFP fusion protein had enzymological characteristics very similar to those of the native delta-PKC and was present throughout the cytoplasm in CHO-K1 cells. ATP at 1 mM caused a transient translocation of delta-PKC-GFP to the plasma membrane approximately 30 s after the stimulation and a sequent retranslocation to the cytoplasm within 3 min. A tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA; 1 microM), induced a slower translocation of delta-PKC-GFP, and the translocation was unidirectional. Concomitantly, the kinase activity of delta-PKC-GFP was increased by these two stimulations, when the kinase activity of the immunoprecipitated delta-PKC-GFP was measured in vitro in the absence of PKC activators such as phosphatidylserine and diacylglycerol. Hydrogen peroxide (H2O2; 5 mM) failed to translocate delta-PKC-GFP but increased its kinase activity more than threefold. delta-PKC-GFP was strongly tyrosine phosphorylated when treated with H2O2 but was tyrosine phosphorylated not at all by ATP stimulation and only slightly by TPA treatment. Both TPA and ATP induced the translocation of delta-PKC-GFP even after treatment with H2O2. Simultaneous treatment with TPA and H2O2 further activated delta-PKC-GFP up to more than fivefold. TPA treatment of cells overexpressing delta-PKC-GFP led to an increase in the number of cells in G2/M phase and of dikaryons, while stimulation with H2O2 increased the number of cells in S phase and induced no significant change in cell morphology. These results indicate that at least three different mechanisms are involved in the translocation and activation of delta-PKC.

Adenosine Triphosphate↗

PubMed1998

Subspecies-specific targeting mechanism of protein kinase C.

To clarify the subspecies-specific functions of protein kinase C (PKC), we constructed cDNAs encoding gamma-, epsilon- and delta-PKC fused with green fluorescent protein (GFP). All fusion proteins had enzymological and immunological characteristics similar to those of native PKCs. When expressed in CHO-K1 cells, each fusion protein showed a specific subcellular localization. Their translocations induced by various stimulation were also diverse. For example, ATP translocated gamma-, epsilon- and delta-PKC-GFP in the cytoplasm to the plasma membrane within 30 sec with a return to the cytoplasm in 3 min, whereas TPA induced slow and irreversible translocation of all subspecies to the plasma membrane. Fatty acids also induced the translocation of gamma- and epsilon-PKC-GFP, but the two PKC subspecies showed distinct translocation and sensitivity to various fatty acids. Furthermore, we revealed that the PKC translocation requires neither the kinase activity of PKC nor its association with cytoskeletal proteins such as F-actin. These results indicate that each subspecies has a spatially and temporally different targeting mechanism that depends on the extracellular and intracellular signals, contributing to the subspecies-specific functions of PKC. These remarkable findings also indicate that a system for monitoring the PKC translocation is a powerful tool for investigating the subspecies-specific functions of PKCs and mechanism of its translocation.

Animals↗

PubMed1998

Moyamoya disease associated with pulmonary sarcoidosis--case report.

A 61-year-old female presented with a unique case of moyamoya disease associated with pulmonary sarcoidosis. She was admitted for sudden onset of left temporalgia with episode of numbness on face, tongue, and upper extremity on the right side. The next morning, she had symptoms of Gerstmann syndrome and her ability to speak was disturbed. Her medical history included radical resection of lung cancer on the right side. She had no symptoms of pulmonary sarcoidosis. Neuroimaging showed an infarction in the left occipital lobe. Angiography showed occlusions of the bilateral internal carotid arteries at the supraclinoid portions. Subsequently, a left superficial temporal artery-middle cerebral artery anastomosis with encephalo-myo-synangiosis was performed. Ninety-three days after admission, she suddenly developed dyspnea which resulted in death 3 hours later. Autopsy findings showed typical epithelioid granulomas of sarcoid type in the lymph nodes of the peribronchus, lung, and liver. Thrombotic emboli were found in the bilateral pulmonary arteries, and marked fibrous intimal thickening in the bilateral internal carotid arteries. Immunological reaction with inflammatory events may cause pathological changes in patients with moyamoya disease or sarcoidosis. The co-incidence in this case suggests that some common inflammatory events may be involved in the pathogenesis of these diseases.

Carotid Artery, Internal↗

PubMed1998

Circulatory arrest with profound hypothermia during the surgical treatment of large internal carotid artery aneurysm--case report.

A 43-year-old male presented with a cerebral aneurysm manifesting as right facial paresthesia, without neurological deficit. Angiography revealed a large aneurysm (22 mm) of the left internal carotid artery. Intravascular treatment using placement of a detachable coil was attempted, but the coil did not stay in the aneurysmal cavity and the procedure was abandoned. The patient did not tolerate the transient balloon occlusion test of the left internal carotid artery. Therefore, the aneurysm was clipped through an open craniotomy with profound hypothermia (20 degrees C) with cardiac arrest (24 minutes). The aneurysmal dome was collapsed, allowing easy dissection of the posterior communicating artery. The closed chest method was used during the extracorporeal cardiopulmonary bypass. Postoperative angiography revealed complete neck clipping with preservation of carotid blood flow. The patient recovered well and resumed his employment. Circulatory arrest with hypothermia provides several benefits for the surgical treatment of large and giant aneurysms.

Adult↗

PubMed1998

Large and giant middle to lower basilar trunk aneurysms treated by surgical and interventional neuroradiological methods.

Treatment of large and giant aneurysms of the basilar artery remains difficult and controversial. Three large or giant aneurysms of the lower basilar artery were treated with a combination of surgical and interventional neuroradiological procedures. All patients underwent the balloon occlusion test with hypotensive challenge (blood pressure reduced to 70% of the control value). The third patient did not tolerate the test. In the first patient, both vertebral arteries were occluded through a craniotomy. In the second patient, both the aneurysm and the basilar artery were occluded by detached balloons. In the third patient, one vertebral artery was occluded by surgical clipping and the other by detached helical coils and fiber coils. In spite of anti-coagulation and anti-platelet therapy, postoperative thrombotic or embolic ischemia occurred in the second and third patients. Fibrinolytic therapy promptly corrected the ischemic symptoms, but the second patient developed hemorrhagic complications at the craniotomy area 2 hours later. At follow-up examination, the first patient had only 8th cranial nerve paresis, the second patient who had a hemorrhagic complication was bed-ridden, and the third patient had no deficit. Interventional occlusion requires a longer segment of the parent artery compared to surgical occlusion of the parent artery and might cause occlusion of the perforating arteries. However, selected use of various coils can occlude only a short segment of the parent artery. Thus, the postoperative management of thromboembolic ischemia after the occlusion of the parent artery is easier using the interventional technique.

Adult↗

PubMed1998

An inverse relationship between serum vitamin C and blood pressure in a Japanese community.

To examine the relationship between serum vitamin C concentration and blood pressure level, a cross-sectional study was conducted. The subjects were 919 men and 1,266 women aged 40 years and over in a Japanese provincial city, Shibata, Niigata Prefecture. The mean and standard deviation of systolic blood pressure (SBP) were 134.0 +/- 20.0 mmHg for men and 128.3 +/- 20.8 mmHg for women, and those of diastolic blood pressure (DBP) were 81.0 +/- 11.7 mmHg and 75.8 +/- 11.4 mmHg, respectively. The mean and standard deviation of serum vitamin C were 42.5 +/- 18.6 mumol/L for men and 56.8 +/- 16.5 mumol/L for women. SBP and DBP were both inversely correlated with serum vitamin C concentration. The means of SBP or DBP were calculated for quartiles of serum vitamin C, and the significant inverse relationship was observed in any sex and age group. The inverse association persisted after adjustment for possible confounders: body mass index, serum total cholesterol, alcohol consumption, smoking, physical activity, antihypertensive medication, and dietary intake of salt, calcium, and potassium. Serum vitamin C appeared to be inversely related with both SBP and DBP in this Japanese population, although further intervention and experimental studies were required to establish the cause-effect relationship.

Adult↗