Biomedical subjects

H Nakai

Publications and source records attributed to H Nakai.

At least 145 records · Page 8Linked to original sources

PubMed1995

Hepatocyte growth factor stimulates liver regeneration and elevates blood protein level in normal and partially hepatectomized rats.

The effects of recombinant human hepatocyte growth factor (HGF) on liver growth and function of normal and partially hepatectomized rats have been examined. HGF was continuously administered into the jugular vein because it was rapidly eliminated from the plasma (t1/2 alpha; approximately 4.5 min) and degraded. In normal rats, the labeling index of hepatocytes was increased about 6 times by the administration of HGF. HGF also decreased the prothrombin time and increased the hepaplastin and serum albumin content. In 70%-hepatectomized rats, HGF stimulated liver regeneration and increased the level of blood proteins such as hepaplastin in a dose-dependent manner. The stimulation of serum protein level seemed to result from not only the increase of hepatic cell number but also the direct effect of HGF on the protein production in hepatocytes, because HGF rapidly enhanced the protein synthesis prior to the increase of cell number and increased the mRNA content of albumin in the liver in vivo. In addition, a combination of heparin with HGF further accelerated the effects of HGF described above, possibly due to the decrease of HGF clearance. These findings suggest that HGF accelerates both the hepatic regeneration and function in vivo, and that rhHGF is clinically expected to be a potent therapeutic agent in hepatectomy and liver injury.

Albumins↗

PubMed1995

Hemizygous expression of the wild-type p53 allele may confer a selective growth advantage before complete inactivation of the p53 gene in the progression of chronic myelogenous leukaemia.

We analysed the expression of the p53 gene in various clinical phases of chronic myelogenous leukaemia (CML) by quantitative reverse transcriptase (RT) polymerase chain reaction (PCR). Hemizygous expression of the wild-type p53 allele was observed in two samples showing the loss of one p53 allele, and affected p53 expression was associated with p53 allelic loss rather than the clinical phase of CML. In four patients with CML showing p53 inactivation, we performed a detailed sequential analysis of p53 allelic loss, p53 mutation and expression from the onset of the disease to the patients' death. Consequently, we demonstrated that the loss of a wild-type p53 allele preceded mutation of the remaining allele, and that cells hemizygous for the wild-type p53 allele dominated those with both wild-type alleles, then were replaced by cells with complete p53 inactivation. These observations indicate that not only complete p53 inactivation but also hemizygous expression of the wild-type p53 allele may confer a selective growth advantage, and that the former is implicated in a more malignant phase than the latter. Alternatively, the inactivation of another undefined anti-oncogene on chromosome 17p may allow selective growth before the p53 mutation occurs.

Alleles↗

PubMed1995

Common inhibitory effects of human anti-C2 domain inhibitor alloantibodies on factor VIII binding to von Willebrand factor.

Factor VIII (FVIII) inhibitor alloantibodies obtained from seven severe haemophilia A patients were examined for their binding regions and their effects on FVIII binding to von Willebrand factor (vWF). Immunoblotting analysis with a panel of recombinant fragments demonstrated that the binding regions of antibodies in cases 1-5 were contained in the C2 domain of the light chain. Antibodies from cases 1 and 2, which recognized an epitope within residues 2248-2312, completely inhibited FVIII/vWF binding in an ELISA (IC50: 5.0 and 9.0 micrograms/ml, respectively). Antibodies from case 3 recognizing 2170-2312 and case 5 recognizing 2170-2327 also inhibited FVIII/vWF binding (IC50: 110 and 400 micrograms/ml, respectively). Case 4 antibodies recognizing 2218-2307 showed barely detectable inhibition and cases 6 and 7 antibodies recognizing the 44 kD heavy chain, did not inhibit. Our results demonstrate that all anti-C2 alloantibodies with epitopes that extend to the residue 2312 inhibit vWF binding and that an overlap of the inhibitor epitope with residues 2308-2312 is critical for maximal inhibition of vWF binding. Prevention of FVIII/vWF binding appears to be a common property of anti-C2 domain inhibitor alloantibodies.

Enzyme-Linked Immunosorbent Assay↗

PubMed1995

Carcinosarcomas of the esophagus.

Two cases of carcinosarcoma of the esophagus are reported. Both were polypoid tumors occurring in the middle of the intrathoracic esophagus. The tumors were predominantly composed of spindle-shaped sarcoma cells with some squamous cell carcinomas (SCC). One tumor showed many bizarre giant cells with filamentous materials in the cytoplasm. Microscopical examination of both tumors revealed transition from SCC to sarcoma cells. Immunohistochemically, the spindle-shaped sarcoma cells in both tumors displayed a strongly positive immunoreaction to alpha-smooth muscle actin, as did the bizarre giant cells of one tumor to sarcomeric actin. SCC and a few spindle-shaped sarcoma cells near the SCC showed a positive immunoreaction to cytokeratin. Electron microscopy revealed that the spindle-shaped cells had many myofilaments with dense bodies and that the bizarre giant cells had sarcomere structures with Z-bands in their cytoplasm. These findings indicate that both tumors were carcinosarcomas of SCC and myogenic sarcoma. We considered that sarcoma cells might originate in SCC, representing its metaplastic differentiation, or that both SCC and sarcoma might originate in a pluripotent stem cell.

Aged↗

PubMed1995

Zonisamide: electrophysiological and metabolic changes in kainic acid-induced limbic seizures in rats.

We studied the pharmacological mechanism of zonisamide (ZNS) using an electrophysiological and autoradiographical method in a limbic seizure model in rats. Limbic seizure status epilepticus was induced by a unilateral microinjection of kainic acid (KA) into the amygdala. Initially, observed seizures were limited to the side of the injected amygdala and then propagated to bilateral sensorimotor cortex. Eighty minutes after injection, secondarily generalized seizure status epilepticus was induced, with each seizure lasting approximately 30 s and recurring every 5 min. ZNS 100 mg/kg was administered intravenously (i.v.) during the generalized seizure. Forty minutes after ZNS administration, epileptic activity was observed only at the KA-injected amygdalar site and spikes were not observed in the bilateral sensorimotor cortex. We studied local cerebral glucose utilization (LCGU) after ZNS or saline administration using an autoradiographical method in the same limbic seizure preparation. In the ZNS group, LCGU decreased in the ipsilateral sensorimotor cortex and hippocampus, whereas in the controls LCGU increased in these structures. On the other hand, ZNS did not suppress the epileptic activity of the primary focus and no decrease in LCGU was observed in the KA-injected amygdala. ZNS inhibited seizure propagation from the epileptogenic focus but did not suppress the epileptic activity of the focus. Our results suggest that ZNS is effective for the treatment of secondarily generalized seizure.

Animals↗

PubMed1995

Long-term follow-up of patients with a history of near fatal episodes; can inhaled corticosteroids reduce the risk of death from asthma?

We retrospectively studied the use of inhaled corticosteroids in patients who experienced near fatal episodes (NFE) to determine whether such therapy reduces the risk of death. Forty-eight patients who had near fatal episodes of asthma between January 1981 and December 1989 were divided into two groups. Group A comprised 19 patients who received beclomethasone dipropionate (BDP) daily (mean dose of BDP:687 micrograms/day: 200-2,000) following NFE, and Group B, 28 patients who did not take BDP or who took less than 6 mg BDP/month. During the follow-up period (Group A:82.9 months, Group B:66.2 months), no patients in Group A died, but eight deaths occurred in Group B (mean period between near fatal episode and death was 31.5 months: 12-66). These results suggest that the regular use of inhaled corticosteroids, even at low doses, may reduce the risk of death in patients who experience NFE.

Acute Disease↗

PubMed1995

Cavernous sinus invasion by pituitary adenomas--relationship between magnetic resonance imaging findings and histologically verified dural invasion.

The relationship between magnetic resonance (MR) imaging findings and histologically verified invasion of the cavernous sinus by tumor cells was studied in 26 patients treated surgically for pituitary adenoma. Dural invasion of the sellar floor by tumor cells was found in 10 cases (38%). All patients were classified according to MR imaging findings into three types. Type I showed a gadolinium-enhanced stripe medial to the carotid artery (5 patients), none of which showed dural invasion. Type II showed no enhanced stripe (17 patients), six of which showed dural invasion. Within this type, tumor size and dural invasion showed no correlation. Type III showed displacement or encasement of the carotid artery by the tumor with or without extracranial extension (4 patients), all of which showed massive infiltration of the tumor cells into the dura mater. This study shows that preoperative MR imaging can provide information for assessment of invasion into the cavernous sinus in patients with pituitary adenoma.

Adenoma↗

PubMed1995

Chromosome 17 abnormalities and inactivation of the p53 gene in chronic myeloid leukemia and their prognostic significance.

We have reviewed all the relevant studies on the loss of the short arm of chromosome 17 (17p) and inactivation of the p53 gene in chronic myelogenous leukemia (CML) in an attempt to clarify their roles in the progression of CML. Loss of a 17p (hemizygous 17p) and p53 inactivation emerged as the disease progressed and were closely associated with each other. About half of the cases with loss of a 17p, however, did not show p53 inactivation. In these cases loss of a 17p preceded p53 inactivation, which suggested that either reduction of the p53 gene dosage or inactivation of another tumor-suppressor gene on 17p might contribute to the disease progression. Both loss of a 17p and p53 inactivation may serve as poor prognostic factors but the prognostic significance of the former only emerged when metaphase cells with loss of a 17p were dominant amongst the total cell population analyzed.

Blast Crisis↗

PubMed1995

Effect of immersion in water on linear expansion and strength of three base/liner materials.

The purpose of this study was to characterize three base/liner materials in the initial stage of setting, i.e., dual-cured (light-activated glass ionomer), light-cured (light-activated glass ionomer analogue), and chemically-cured (conventional glass ionomer) materials. Changes in dimension, weight and flexural strength were examined from immediately after setting to the end of one week following immersion in water. The results obtained from these three types of material differed from each other, and showed a statistically significant correlation between changes in dimension and weight. This may be attributed to hygroscopic expansion. They also showed different flexural strength, indicating differences in the polymerization system. From these results, it appeared that marginal gaps following setting would be compensated for by hygroscopic expansion during immersion in water for one day or more. Physical properties would be favourably improved following the setting process which continues to advance during immersion in water.

Absorption↗

PubMed1995

Salfredins, new aldose reductase inhibitors produced by Crucibulum sp. RF-3817. I. Fermentation, isolation and structures of salfredins.

New inhibitors of aldose reductase, designated salfredins A3, A4, A7, C1, C2, C3 and B11, were isolated from the fermentation broth of Crucibulum sp. RF-3817 by successive purification procedures of solvent extraction, silica gel column chromatographies and reverse-phase HPLC. Their structures were established by spectroscopic methods, including UV, SI-MS and NMR. The structures of salfredins A4 and B11 were confirmed by X-ray crystallographic analysis.

Aldehyde Reductase↗

PubMed1995

[Posttraumatic pseudoaneurysm of the middle meningeal artery: a case report].

An epidural hematoma associated with posttraumatic pseudoaneurysm of the middle meningeal artery is a very rare clinical entity. Only 31 such cases have been reported in the literature. A 54-year-old man was admitted with lethargy and right hemiparesis. A skull X-ray film revealed a linear fracture in the left parietal and temporal bone, extending to the base of the skull. A brain CT scan disclosed an acute epidural hematoma over the left cerebral hemisphere, contusional hematoma in the right frontal lobe and thalamus, and subarachnoid hemorrhage in the left Sylvian fissure. During an emergency craniotomy a large epidural hematoma was evacuated and external decompression was performed. Angiography, which was performed about one month after the head injury, revealed an aneurysm of the middle meningeal artery. The aneurysm was removed to avoid delayed rupture at the time of cranioplasty. Histological diagnosis was pseudoaneurysm. We discussed the pathogenesis of a pseudoaneurysm of the meningeal artery and the necessity to pay attention to the presence of a pseudoaneurysm when an active bleeding point is not observed during surgery of the epidural hematoma.

Aneurysm, False↗

PubMed1995

[Aneurysm surgery using temporary occlusion under SEP monitoring].

Premature rupture of a cerebral aneurysm during operation is a serious hazard. Temporary occlusion of intracranial arteries has emerged as a valuable technical adjunct in the management of intracranial aneurysms. Twenty-five patients (from a group of 43 consecutive aneurysm patients treated during a 13-month period) underwent elective temporary arterial occlusion under somatosensory evoked potential (SEP) monitoring. Median nerve SEPs were used during 19 ICA and MCA aneurysm operations, while posterior tibial SEPs only were used in 7 patients with aneurysm of the ACA. Amplitude of the N20 or P40 was evaluated. A decrease in amplitude more than 50% when compared to baseline value was defined as a significant SEP change. In 11 patients of the 25 cases, SEP changes were observed. Temporary occlusion was applied to the proximal portion of the internal carotid artery 10 times, to the M1 portion of the middle cerebral artery 5 times, to the M1-M2 complex 5 times, to the A1 portion of the anterior cerebral artery 9 times, and to the A2 - A3 once. Of the 26 clipping (25 patients), 12 had SEP alterations, 14 had no SEP changes. Temporary occlusion was released within 3 minutes after disappearance of N20 (or P40) in all the patients with SEP changes except one. Nine of these 11 patients showed complete recovery of SEP and two showed partial recovery. Patients with partial recovery of SEP were associated with postoperative new neurological deficit, which was transient in one of them. There was a correlation between changes in SEP and post operative outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

[Cisplatin, 5-fluorouracil and leucovorin combination chemotherapy-added radiation therapy for advanced esophageal cancer--a case report].

Cisplatin, 5-fluorouracil and leucovorin combination chemotherapy added radiation therapy was performed for the treatment of 62-year-old male patient with advanced esophageal cancer who had liver cirrlosis. After the treatment, esophageal lesion disappeared. Only minimal side effect occurred during the treatment. Biochemical modulation chemotherapy combined with radiation therapy is useful for advanced esophageal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

[Double uterus and double vagina with unilateral imperforate vagina associated with ipsilateral renal agenesis: an infant case report].

Duplicated uterus associated with unilateral imperforate vagina and ipsilateral renal agenesis is a very rare anomaly. We report a case of a 10-month-old female infant presenting with pus discharge from vagina, and discussed the embryologic and clinical features relevant to this interesting disease complex with a review of the past literature. Echographic and CT examinations demonstrated a right-sided cystic pelvic mass. IVP revealed a left slight hydronephrosis and non-visualizing right kidney. No right ureteral orifice was found at cystoscopy. Under anesthesia the mass and pus was aspirated. Under the diagnosis of Gartner's cystic duct and a right renal agenesis or dysplasia with or without ectopic ureter, we subsequently performed laparotomy. Surgical exploration revealed a duplicated uterus with a normal ovary, and the mass was an imperforate right-sided vagina which communicated through the uterus. The diagnosis was changed to a double uterus with right-sided imperforate vagina, then the vaginal septum was excised. The post-operative course was uneventful, and pus discharge and the left hydronephrosis have disappeared.

Female↗

PubMed1995

Inhibition of Df-protease--induced kinin release by synthetic inhibitors.

A protease (Df-protease) from house dust mite (D. farinae) is closely associated with mite-induced allergy: Df-protease has a similar substrate specificity to blood coagulation factor XIIa and catalyzes the activation of kallikrein-kinin system in human plasma. With the purpose of prevention of kinin-formation in plasma by Df-protease, inhibition of Df-protease with synthetic inhibitors was tested in vivo and in vitro. Among the inhibitors, including amidine and guanidine derivatives, N-allyl-N-[4-(4-amidinophenoxycarbonyl)-alpha-methylcinnamoyl++ +]glycine ethyl ester mesylate was the most effective to inhibit Df-protease with Ki = 9 x 10(-9) M and also to prevent kinin-release from Df-protease in human plasma. Enhancement of vascular permeability in guinea pigs caused by kinin-release was stoichiometrically suppressed by the inhibitor.

Amidines↗

PubMed1994

Determination of a new H(+)-K+ ATPase inhibitor (E3810) and its four metabolites in human plasma by high-performance liquid chromatography.

A method for the simultaneous determination of E3810, 2-[(4-(3-methoxypropoxy)-3-methyl pyridine-2-yl)methyl sulfinyl]-1H-benzimidazole sodium salt and its four metabolites, demethylated-E3810 (DM), demethylated thioether-E3810 (DMTE), sulfone-E3810 (S), and thioether-E3810 (TE), in human plasma by high-performance liquid chromatography (HPLC) with UV absorbance detection has been established. The correlation coefficient for all the standard curves was 0.998 or greater. The quantitation limit was 5 ng/ml for E3810 and 20 ng/ml for each of its four metabolites. The recovery of E3810 and its four metabolites from human plasma was high, being greater than 80% when 100 ng of each substance was added per tube, except for DM (74.1%). The stability of E3810 and its four metabolites was evaluated and the following results were obtained: (1) when samples were centrifuged within 20 min after collection, there was no loss of E3810 or its metabolites; (2) when 100 microliters of a 1% aqueous solution of diethylamine was added within 20 min after plasma isolation, there was no loss of E3810 or its metabolites; and (3) there were no stability problems during storage for a period of 10 months at -20 degrees C.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1994

Participation of the bacteriophage Mu A protein and host factors in the initiation of Mu DNA synthesis in vitro.

During bacteriophage Mu transposition, strand transfer is catalyzed in the presence of phage-encoded A and B proteins and Escherichia coli HU protein, attaching Mu ends to target DNA and creating an intermediate in transposition. Bacteriophage Mu A protein, which remains tightly bound to the Mu ends in the native strand-transfer intermediate, blocked initiation of Mu DNA replication by a system of 8 host proteins (DnaB helicase, DnaC protein, DnaG primase, DNA polymerase III holoenzyme, DNA polymerase I, DNA gyrase, DNA ligase, and single-strand binding protein). This 8-protein system had all enzymatic activities to convert the deproteinized intermediate to a cointegrate; however, additional host factor(s) were required to replicate the native intermediate. While replication of the native intermediate absolutely required DnaB helicase, DnaC protein, and DNA polymerase III holoenzyme, the specific requirements were relaxed for the deproteinized intermediate. Other host factors were able to replace these specific factors. These results indicate that Mu A protein, in conjunction with additional host factor(s), acts to promote assembly of specific host replication proteins at the Mu replication fork. This process may alter the stable interaction of Mu A protein with the ends to allow initiation of Mu DNA synthesis.

Bacterial Proteins↗

PubMed1994

Myelomonocytic crisis with t(5;17) and a p53 mutation in a patient with chronic myelogenous leukemia.

We report a 64-year-old Japanese man with chronic myelogenous leukemia (CML) who expired with myelomonocytic crisis. Cytogenetic analyses of chronic phase (CP) and accelerated phase (AP) cells revealed a Philadelphia chromosome and an isochromosome for the long arm of chromosome 17, i(17q). This karyotype was replaced by another karyotype in blast crisis (BC), resulting in near triploidy with t(5;17) (p15;p11) and loss of chromosome 17 pter-->p11. Interphase fluorescent in situ hybridization studies with a chromosome 17 specific alpha satellite DNA probe confirmed the presence of a clonal change in BC. In addition, single-strand conformation polymorphism analysis and PCR-direct sequencing of BC cells revealed a point mutation at codon 203 of the p53 gene, GTG to GAG (Val to Glu), and loss of the normal allele. In contrast, no alterations of the p53 gene were found in CP and AP cells. Therefore, progression of CML in this patient appeared to be related to loss of 17p, as well as a mutation in the p53 gene.

Alleles↗