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Biomedical subjects

H Nakai

Publications and source records attributed to H Nakai.

At least 55 records · Page 3Linked to original sources
PubMed2000

Reaction of 3-acetonyl-5-cyano-1,2,4-thiadiazole with phenylhydrazine hydrochlorides: indolization and phenylpyrazolation.

Treatment of 3-acetonyl-5-cyano-1,2,4-thiadiazole (1) with 4-methyl or 4-methoxyphenylhydrazine hydrochloride provided 5-cyano-3-(2,5-dimethylindol-3-yl)-1,2,4-thiadiazole (2) or 5-cyano-3-(5-methoxy-2-methylindol-3-yl)-1,2,4-thiadiazole (3) as the sole product, respectively. In contrast, treatment of 1 with phenylhydrazine hydrochloride resulted in the formation of 5-cyano-3-(2-methylindol-3-yl)-1,2,4-thiadiazole (4) and the unexpected 5-cyano-3-(3,5-dimethyl-1-phenylpyrazol-4-yl)-1,2,4-thiadiazole (5). In a similar manner, when 1 was treated with 4-chlorophenylhydrazine hydrochloride, indolization was suppressed by phenylpyrazolation giving rise to 5-cyano-3-(5-chloro-2-methylindol-3-yl)-1,2,4-thiadiazole (6) and 5-cyano-3-[1-(4-chlorophenyl)-3,5-dimethylpyrazol-4-yl]-1,2,4-thia diazole (7). The reaction mechanism is discussed. Compounds 4, 5 and 6 exhibited weak antimicrobial activity against Helicobacter pylori.

Anti-Bacterial Agents↗
PubMed2000

Clinical evaluation of vascularized bone grafts and osseointegrated implants.

We evaluated mandibular rehabilitation using vascularized bone graft and osseointegrated implants. Questionnaires were used to evaluate the masticatory function, and we measured the occlusal force in each patient. In addition, we measured the height of grafted bone to assess the possible relationship between masticatory rehabilitation and the change in bony height. Five of 13 patients showed over 12.0% increase in bony height after superstructure fabrication. Most of the patients who underwent tongue resection scored low points on the questionnaire. Also, most patients with resection, including resection of the angles of the mandible, showed a lower occlusal force than those without.

Adult↗
PubMed2000

[A case of the syndrome of the sinking skin flap: case report].

A case of "the syndrome of the sinking skin flap" was presented. A 40-year-old-man had suffered from severe SAH 9 months before. An aneurysm of the anterior communicating artery was successfully clipped and the bone flap was removed for the purpose of the external decompression. Cranioplasty and V-P shunt were performed 1 month after SAH, but both were removed because of postoperative wound infection, viz. epidural and subdural abscess 4 months after SAH. Following this, L-P shunt was performed, and the patient was discharged with mild dementia. A concave deformity of the skin flap developed about 4 months after the L-P shunt. Neurological examination showed progressive left hemiparesis and akinetic mutism. A low CSF pressure was demonstrated, but RI cisternography revealed normal CSF circulation. Intrathecal infusion of the artificial CSF was carried out via lumbar puncture and concavity of the skin flap gradually improved. This procedure resulted in improvement of the neurological deficits. Cranioplasty with artificial bone was performed under continuous intrathecal infusion of the artificial CSF. Postoperative course was satisfactory and neurological examination revealed only mild dementia. The pathological mechanism in our case was probably due to the compression of the brain by the atmospheric pressure following the external decompression. Moreover, L-P shunt exaggerated this pathology by the overdrainage of CSF.

Adult↗
PubMed2000

Gene delivery to human chondrocytes by an adeno associated virus vector.

OBJECTIVE: To investigate the efficiency of gene transduction to human chondrocytes using an adeno associated virus (AAV) vector. METHODS: We transduced green fluorescent protein (GFP) gene using AAV vector to primary human chondrocytes as well as human cartilage organ cultures, in which chondrocytes are surrounded by extracellular matrix. Expression of GFP gene was analyzed at various time points after transduction by fluorescence microscopy and immunohistochemistry. RESULTS: In primary chondrocytes, the percentages of GFP positive cells were 15.9% or 16.0% on Day 1 and 95.0% or 93.7% on Day 7 after gene transduction. In cartilage organ cultures, gene delivery was observed in cells located not only in the superficial layer but also in the deep layer within the cartilage tissue. Up to 45.3+/-7.4% or 46.0+/-3.9% of chondrocytes expressed GFP for at least 28 days. CONCLUSION: AAV vector could be useful for direct gene delivery to chondrocytes in situ.

Adenoviridae↗
PubMed2000

[A case of advanced rectal cancer with unresectable liver metastasis for which chemotherapy was markedly effective].

We report a case of advanced rectal cancer accompanied by unresectable liver metastasis in which remission has been achieved for 7 years. The patient was a 64-year-old woman, and her chief complaints were a feeling of abdominal distention and melena. After low anterior resection (D3), oral administration of 600 mg/day of UFT-E and chemotherapy against the liver metastasis by hepatic arterial injection via a reservoir were started. Since the arterial injection via a reservoir became impossible due to infection, her clinical course was observed solely with oral administration of UFT-E. As a result, complete remission was achieved 7 months postoperatively, and the patient is still alive in good health without recurrences at present (7 years postoperatively). The reason why a favorable outcome has been achieved is probably that, although the initial operation resulted is non-curative resection, measures sufficient to enable the patient to lead an ordinary social life were taken at the beginning, and efforts to achieve a long-term survival were made while respecting the quality of life of the patient so that the patient would be able to coexist with the cancer.

Adenocarcinoma↗
PubMed1999

Coexpression of factor VIII heavy and light chain adeno-associated viral vectors produces biologically active protein.

We are interested in using recombinant adeno-associated viral vectors in the treatment of hemophilia A. Because of the size constraints of recombinant adeno-associated viral vectors, we delivered the heavy and light chains of the human factor 8 (hFVIII) cDNA independently by using two separate vectors. Recombinant AAV vectors were constructed that utilized the human elongation factor 1alpha promoter, a human growth factor polyadenylation signal, and the cDNA sequences encoding either the heavy or light chain of hFVIII. Portal vein injections of each vector alone, a combination of both vectors, or a hFIX control vector were performed in C57BL/6 mice. An ELISA specific for the light chain of hFVIII demonstrated very high levels (2-10 microgram/ml) of protein expression in animals injected with the light chain vector alone or with both vectors. We utilized a chromogenic assay in combination with an antibody specific to hFVIII to determine the amount of biologically active hFVIII in mouse plasma. In animals injected with both the heavy and light chain vectors, greater than physiological levels (200-400 ng/ml) of biologically active hFVIII were produced. This suggests that coexpression of the heavy and light chains of hFVIII may be a feasible approach for treatment of hemophilia A.

Animals↗
PubMed1999

Duplex opening by primosome protein PriA for replisome assembly on a recombination intermediate.

PriA and other primosome assembly proteins of Escherichia coli recruit the major replicative helicase DnaB for replisome assembly during bacteriophage Mu transposition and replication. MuA transposase catalyzes the transfer of Mu ends to target DNA, forming a potential replication fork that provides the assembly site for the replisome. However, this fork lacks the single-stranded DNA needed to load DnaB. Although no pre-existing primosome assembly sites that bind PriA were found within the Mu end sequences, PriA was able to bind to the forked DNA structure created by MuA. The helicase activity of PriA could then open the duplex to create the DnaB binding site. In a tightly coupled reaction on synthetic forked substrates, PriA promoted both the unwinding of the lagging strand arm and preprimosome assembly to load DnaB onto the lagging strand template. PriA apparently translocated 3' to 5' along the lagging strand template until sufficient single-stranded DNA was exposed for binding of DnaB, which then translocated 5' to 3' in the opposite direction. Mutant PriA lacking helicase activity was unable to promote this process, and loss of PriA helicase impaired Mu DNA replication in vivo and in vitro. This suggests that the opening of the duplex by PriA helicase is a critical step in the initiation of Mu DNA replication. Concerted helicase and primosome assembly functions would allow PriA to act as initiator on recombination intermediates and stalled replication forks. As part of the replisome, PriA may act as a mobile initiator that minimizes interruptions in chromosomal replication.

Bacterial Proteins↗
PubMed1999

Is barium enema reduction safe and effective in patients with a long duration of intussusception?

The aim of this study was to determine whether barium enema reduction (BER) is safe and effective in patients with a long duration of intussusception. Over the last 17 years, 104 patients were admitted to our hospital with a diagnosis of intussusception. All except 1 with peritonitis underwent BER primarily. Of the 103 intussusceptions treated primarily by BER, 84 (82%) were reduced by the enema alone, whereas 19 (18%) underwent surgical reduction. There were no differences in mean duration of disease between the patients with successful and failed enema reduction (successful: 15 +/- 14 h; failures: 14 +/- 11 h, P = 0.6). The success rate of BER was 85% within 12 h of symptoms, 76% for 12-24 h, and 71% for more than 24 h. Of 8 cases with a second trial, 4 (50%) were reduced by repeated barium enema. There were no deaths and no intestinal perforations. The success rate of more than 70% even in patients with a long duration of intussusception suggests that BER is safe and effective regardless of the duration of the disease.

Barium Sulfate↗
PubMed1999

Antioxidants from Lespedeza homoloba. (I).

The stems of Lespedeza homoloba yielded eight new and three known phenolic compounds. Their structures have been elucidated on the basis of their spectral data. These compounds had strong antioxidative activity against lipid peroxidation in the rat brain homogenate test. 3,9-Dihydroxypterocarp-6a-en and lespedezol A2 showed significant antiallergic activity in allergic (type I) mice.

Animals↗
PubMed1999

Identification of a factor VIII peptide, residues 2315-2330, which neutralizes human factor VIII C2 inhibitor alloantibodies: requirement of Cys2326 and Glu2327 for maximum effect.

Factor VIII (FVIII) inhibitor alloantibodies react with combinations of the A2, C2 and A3-C1 domains of the FVIII molecule. Some inhibitors block binding of FVIII to both von Willebrand factor (VWF) and phospholipid, and recognize a C2 domain epitope which overlaps both binding sites. In order to determine the essential binding regions for alloantibodies inhibitory for FVIII activity, we have performed inhibitor neutralization assays and competitive inhibition assays using 10 overlapping synthetic peptides spanning the carboxy-terminal region of the C2 domain (residues 2288-2332). We found one peptide (2315-2330, L9) which neutralized the anti-FVIII activity of four out of five different C2 alloantibodies by 50%, 39%, 47% and 57%, respectively. Neutralization of these alloantibodies by recombinant C2 domain (residues 2173-2332) was 68%, 50%, 59%, 86% and >95%, respectively. The inhibitor which was not neutralized by L9 peptide and reacted by immunoblotting with peptide 2218-2307, did not prevent binding of FVIII to VWF and only partially inhibited binding of FVIII to phosphatidylserine. Mutants of the L9 peptide were prepared in which each residue from 2315-2330 was sequentially substituted by glycine. Inhibitor neutralization experiments using these peptides demonstrated that Arg2320 and Cys2326 or Glu2327 are important for the effect of L9 peptide, since their substitution by glycine reduced its neutralizing effect by 60% to >90%, suggesting that they are crucial for formation of the one of the C2 inhibitor epitopes.

Amino Acid Sequence↗
PubMed1999

Starvation-induced Mucts62-mediated coding sequence fusion: a role for ClpXP, Lon, RpoS and Crp.

The formation of araB-lacZ coding sequence fusions in Escherichia coli is a particular type of chromosomal rearrangement induced by Mucts62, a thermoinducible mutant of mutator phage Mu. Fusion formation is controlled by the host physiology. It only occurs after aerobic carbon starvation and requires the phage-encoded transposase pA, suggesting that these growth conditions trigger induction of the Mucts62 prophage. Here, we show that thermal induction of the prophage accelerated araB-lacZ fusion formation, confirming that derepression is a rate-limiting step in the fusion process. Nonetheless, starvation conditions remained essential to complete fusions, suggesting additional levels of physiological regulation. Using a transcriptional fusion indicator system in which the Mu early lytic promoter is fused to the reporter E. coli lacZ gene, we confirmed that the Mucts62 prophage was derepressed in stationary phase (S derepression) at low temperature. S derepression did not apply to prophages that expressed the Mu wild-type repressor. It depended upon the host ClpXP and Lon ATP-dependent proteases and the RpoS stationary phase-specific sigma factor, but not upon Crp. None of these four functions was required for thermal induction. Crp was required for fusion formation, but only when the Mucts62 prophage encoded the transposition/replication activating protein pB. Finally, we found that thermally induced cultures did not return to the repressed state when shifted back to low temperature and, hence, remained activated for accelerated fusion formation upon starvation. The maintenance of the derepressed state required the ClpXP and Lon host proteases and the prophage Ner-regulatory protein. These observations illustrate how the cts62 mutation in Mu repressor provides the prophage with a new way to respond to growth phase-specific regulatory signals and endows the host cell with a new potential for adaptation through the controlled use of the phage transposition machinery.

ATP-Dependent Proteases↗
PubMed1999

Clinical application of a nonpenetrating microvascular stapling device for vascularized free tissue transfer.

It is essential to develop a method that is technically easier and faster to perform microvascular anastomosis. Therefore the authors have utilized a nonpenetrating microvascular stapling device (VCS; Auto Suture, Tokyo, Japan). Eight vascularized free tissue transfers were performed using this stapling device. All of the transferred tissues were grafted successfully. The time required to perform the stapled microvascular anastomosis ranged from 8 to 18 minutes (mean, 12 minutes). Two arterial anastomoses required suture repairs because they could not be repaired with the use of this stapling device due to thickened vessel walls and intimal dissections. The microvascular stapling device proved useful for vascularized free tissue transfers, but the vessels suitable for this technique should be chosen carefully. Not only the surgeon but also the assistant must be experienced in microscopic surgery.

Adult↗
PubMed1999

Isolation of recombinant adeno-associated virus vector-cellular DNA junctions from mouse liver.

Recombinant adeno-associated virus (rAAV) vectors allow for sustained expression of transgene products from mouse liver following a single portal vein administration. Here a rAAV vector expressing human coagulation factor F.IX (hF.IX), AAV-EF1alpha-F.IX (hF.IX expression was controlled by the human elongation factor 1alpha [EF1alpha] enhancer-promoter) was injected into mice via the portal vein or tail vein, or directly into the liver parenchyma, and the forms of rAAV vector DNA extracted from the liver were analyzed. Southern blot analyses suggested that rAAV vector integrated into the host genome, forming mainly head-to-tail concatemers with occasional deletions of the inverted terminal repeats (ITRs) and their flanking sequences. To further confirm vector integration, we developed a shuttle vector system and isolated and sequenced rAAV vector-cellular DNA junctions from transduced mouse livers. Analysis of 18 junctions revealed various rearrangements, including ITR deletions and amplifications of the vector and cellular DNA sequences. The breakpoints of the vector were mostly located within the ITRs, and cellular DNA sequences were recombined with the vector genome in a nonhomologous manner. Two rAAV-targeted DNA sequences were identified as the mouse rRNA gene and the alpha1 collagen gene. These observations serve as direct evidence of rAAV integration into the host genome of mouse liver and allow us to begin to elucidate the mechanisms involved in rAAV integration into tissues in vivo.

Animals↗
PubMed1999

Image-guided epilepsy surgery.

Interactive image-guided techniques used in conjunction with three-dimensional images allow accurate planning and performance of a variety of neurosurgical procedures. The frameless stereotactic Viewing Wand System was used to provide real-time correlation of the operating field and computerized images in over 22 neurosurgical operations carried out for intractable epilepsy. The overall results of the surgery demonstrated favorable results, with class 1 + class 2 outcomes in 86.4% of the present series. Our experience shows that the Viewing Wand System is most helpful as an adjunctive navigational device in the microsurgical treatment of epilepsy.

Adolescent↗
PubMed1999

[Refluxing megaureter in infancy--the significance of differentiation from primary high grade VUR].

BACKGROUND: Recent advance of perinatal ultrasound screening and/or physician's awareness of renal damage from recurrent pyelonephritis has brought about the increasing number of infants with primary vesicoureteral reflux (VUR) including refluxing megaureter which should be conceptually differentiated from simple high grade VUR. We evaluated the clinical outcome of infants diagnosed with refluxing megaureter. PATIENTS AND METHODS: We retrospectively reviewed the clinical records of 15 infants (17 ureters) diagnosed as refluxing megaureter (max caliber > or = 10 mm) at our institution from 1988 to 1997. We compared the clinical outcome of refluxing megaureter with that of high grade VUR. (Results) Patients were 13 boys and 2 girls. Megaureter was unilateral in 13 patients and bilateral in 2. Fourteen infants (93.3%) presented with febrile urinary tract infection (UTI). The diameter of megaureter was 10-21 mm (average: 13.6 +/- 4.0 mm) at excretory urogram. Nine of 15 infants (60.0%) had breakthrough urinary infection. Its incidence was significantly higher than that of high grade VUR (21.3%) (p = 0.02). In 13 cases surgical treatments were performed, however 2 cases (max caliber: 16 mm, 21 mm) by Politano-Leadbetter or Paquin procedure required re-ureteroneocystostomy by Psoas-hitch procedure because of persistent reflux and recurrent UTI. On the other hand no patient required re-ureteroneocystostomy in high grade VUR. CONCLUSION: It is important to differentiate refluxing megaureter from high grade VUR due to high incidence of breakthrough UTI. Ureteral remodeling and/or Psoas-hitch procedure are strongly recommended for adequate length of submucosal tunnel in refluxing megaureter.

Cystostomy↗