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Biomedical subjects

S Nakata

Publications and source records attributed to S Nakata.

At least 37 records · Page 2Linked to original sources

X-ray diffraction study on ordered, disordered and reconstituted intercellular lipid lamellar structure in stratum corneum.

From small angle X-ray diffraction for the stratum corneum of hairless mouse, it was obtained that in the normal stratum corneum, the 1st, 2nd and 3rd order diffraction peaks for the intercellular lipid lamellar structure appear at 13.8, 6.87 and 4.59 nm, respectively and also a broad hump for the 4th order reflection appears as observed by the previous researchers. In the damaged stratum corneum prepared by the treatment of sodium dodecyl sulfate, these small-angle diffraction peaks disappear and only the broad maxima remain around the 1st, 2nd and 3rd order diffraction peaks. These facts indicate that in the normal stratum the lamellar structure is ordered and in the damaged stratum corneum the lamellar structure is disordered. Furthermore, in the reconstituted lamellar structure obtained by immersing into the dilute suspension of the mixture of ceramide 3, cholesterol and stearic acid, the 1st, 2nd and 3rd order diffraction peaks reappear at 13.3, 6.67 and 4.44 nm, respectively. This fact indicates that the reorganization of the ordered lamellar structure takes place by adding the mixture to the damaged stratum corneum.

Animals↗

Sensitive detection and differentiation of Sapporo virus, a member of the family Caliciviridae, by standard and booster nested polymerase chain reaction.

Norwalk virus and Sapporo virus (SV) were approved as type species of the genus Norwalk-like viruses and the genus Sapporo-like viruses, respectively, in the family Caliciviridae. Nested polymerase chain reaction (PCR), using newly designed primers in the RNA-dependent RNA polymerase region, was developed to detect and differentiate viruses in the three genetic groups of SV based on the relative size of the PCR products obtained. In addition, a booster nested PCR that performs nested PCR in a single tube was introduced to reduce the chance of contamination during the procedure of standard nested PCR. The specificity of the newly developed PCR was confirmed by testing 77 stool specimens and 16 tissue culture fluids derived from growth of unrelated viruses. The sensitivity of the nested PCR was compared with the conventional PCR using Sapp35/Sapp36 primer pair by testing the three cDNA clones obtained from viruses in the SV/SV82, the SV/London92, and the SV/Parkville virus, respectively. This assay can detect SV in a more sensitive way than the conventional PCR and Southern hybridization. Sensitive and suitable methods to detect and differentiate SV are required to obtain accurate epidemiological data on these viruses and the standard and booster nested PCR should be a very useful tool for this purpose.

Caliciviridae↗

Expression of cathepsin K mRNA and protein in odontoclasts after experimental tooth movement in the mouse maxilla by in situ hybridization and immunoelectron microscopy.

This study demonstrated the simultaneous expression of cathepsin K (CK) mRNA by in situ hybridization and CK protein by immunoelectron microscopy in odontoclasts in mouse maxillae after experimental tooth movement. On the pressure side (the area under pressure during tooth movement), CK mRNA was detected in odontoclasts in resorption lacunae in the tooth root, in osteoclasts in bone resorption lacuane, and in fibroblasts in the periodontal ligament. Using electron microscopy, CK protein was detected at the apex of odontoclasts, intracellularly in vesicles and granules, and extracellularly in irregularly shaped vacuoles (extracellular spaces), on the plasma membrane of the ruffled border, and on and between typical striated type I collagen fibrils in the lacunae. These vesicles and granules appeared to fuse with irregular vacuoles containing CK-positive fragmented fibril-like structures close to the ruffled border. In the basolateral portion of odontoclasts, small amounts of CK-positive rough endoplasmic reticulum (ER) were found. CK-positive intracellular vacuoles (not extracellular spaces) also appeared to fuse with the vesicles and granules. However, these fused organelles rarely contained fragmented fibril-like structures. They are probably endolysosomes. The distribution of CK in odontoclasts was similar to that previously seen in osteoclasts. Furthermore, CK-positive fibril-like structures were found in the vacuoles of fibroblasts. These results indicated that during tooth movement CK is synthesized in odontoclasts on the pressure side and secreted into the tooth resorption lacunae. Therefore, CK may take part in the degradation of the dentin matrix (type I collagen fibrils and non-collagenous protein) of the tooth root, and in the subsequent intracellular degradation of endocytosed fragmented fibril-like structures in endolysosomes.

Animals↗

Surgical strategy for cholesteatoma in children.

OBJECTIVE: We reviewed our experience with childhood cholesteatoma in children under 15 years old. Based on cumulative postoperative data, we propose a modified canal-wall-up technique in conjunction with a planned, staged operation. METHODS: From 1982 to 1997, 56 children with cholesteatoma (58 ears, total) underwent surgery in our department. In the early period (1982-1990), canal wall-down mastoidectomy was performed in 52% (21 of 40 ears), and canal wall-up mastoidectomy in 48% (the remaining 19 ears). In the late period (1991-1997), 18 ears with cholesteatoma underwent surgery. The canal-wall up mastoidectomy was performed in 89% (16 ears), and canal-wall-down mastoidectomy in the remaining 11% (two ears). RESULTS: In the early period (1982-1990), cholesteatoma recurred more frequently in the canal-wall-up mastoidectomy group than in the canal-wall down mastoidectomy group (53 vs. 14%). Other postoperative complications, such as erosion of the mastoid cavity, otorrhea, and perforation of the eardrum, occurred more frequently in the canal-wall-down mastoidectomy group than in the canal-wall-up mastoidectomy group. In the late period (1991-1997), in the canal-wall-up mastoidectomy group, ten ears underwent one-stage surgery. Planned staged tympanoplasty was completed in six ears. After one-stage surgery, four of ten ears experienced residual cholesteatoma. Two of the recurrent ears had undergone planned staged tympanoplasty. As revealed by postoperative computed tomography (CT) images, 12 of 15 ears had aeration in the attic and antrum as well as in the tympanic cavity. In these cases, no attic retraction pocket formation was observed. CONCLUSION: Our strategy for pediatric cholesteatoma in the future is to use canal-wall-up mastoidectomy when possible. If aeration in the attic and antrum is observed by preoperative CT-scan image and no erosion in the malleus and incus exists, the one-stage surgery will be chosen. If no aeration is observed by CT-scan and/or erosion exists in the surgical findings, planned staged tympanoplasty will be necessary. This strategy allows a high incidence of aeration of the attic and antrum, and prevents the formation of the attic retraction pocket while enabling the early detection of residual cholesteatoma by means of CT.

Adolescent↗

Synthesis and biological evaluation of prodrug-type anti-HIV agents: ester conjugates of carboxylic acid-containing dipeptide HIV protease inhibitors and a reverse transcriptase inhibitor.

On the basis of substrate transition-state mimic concept of HIV protease, a series of small-sized dipeptide inhibitors containing hydrophilic carboxyl group were designed and synthesized. These dipeptide inhibitors showed good HIV protease inhibitory activity, but their anti-HIV activity was poor. The low antiviral activities of these inhibitors were probably due to their inadequate cell membrane permeability caused by the presence of a free carboxylic acid in the inhibitors. Based on the prodrug concept as well as the combination of two different classes of anti-HIV agents, conjugates of HIV protease inhibitors with a nucleoside reverse transcriptase inhibitor were synthesized. Some of these conjugates exhibited excellent antiviral activity compared with that of individual inhibitors. The synergistic enhancement of anti-HIV activities of these conjugates may be due to their ability to penetrate into the target cell and subsequent regeneration of two different classes of anti-HIV agents in the cytoplasm.

Animals↗

Multiple endocrine neoplasia type 2B.

We report a case of multiple endocrine neoplasia type 2B (MEN 2B) in a 30-year-old woman. There was no family history of MEN 2B in her family. DNA testing was carried out and a point mutation was found in exon 16, codon 918 (ATG to ACG) in the RET proto-oncogene. The woman died of medullary thyroid carcinoma, 13 years after a total thyroidectomy.

Adrenal Gland Neoplasms↗

Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene.

We describe 2 siblings with multiple gastrointestinal stromal tumors (GISTs) and cutaneous hyperpigmentation. Both had a point mutation of the c-kit gene. The patients were sisters who had exhibited cutaneous hyperpigmentation since their late teens, but the diagnosis of multiple gastrointestinal submucosal tumors was not made until they were 41 and 45 years old. Histologic examination showed that these tumors were GISTs expressing CD34 and Kit protein. Both patients died of GISTs. Single-strand conformation polymorphism analysis showed a mutation of c-kit in tumor DNA extracted from paraffin-embedded specimens. Direct sequencing analysis showed that the point mutation occurred at codon 559 of exon 11 (Val-->Ala). The same single-point mutation was detected in DNA extracted from peripheral leukocytes obtained from the younger sister and her 2 children (who had similar general hyperpigmentation) as well as in DNA from a skin biopsy specimen taken from the older sister. The germline mutation at codon 559 of the c-kit gene found in the present familial GISTs differed from that in a previously reported case of familial GISTs. We propose that GISTs caused by a germline mutation of the c-kit gene should be referred to as GIST-cutaneous hyperpigmentation disease.

Adult↗

Moderate dose diethylstilbestrol diphosphate therapy in hormone refractory prostate cancer.

OBJECTIVE: To examine the efficacy and toxicity of a moderate dose (250 mg/day) of diethylstilbestrol diphosphate (DES-DP) intravenously administered to patients with hormone refractory prostate cancer (HRPC) as well as the influence of this agent on the endocrine system. PATIENTS AND METHODS: Sixteen patients with HRPC were treated with a daily intravenous injection of 250 mg of DES-DP for 28 days. Eastern Cooperation Oncology Group (ECOG) performance status and pain score were used for subjective evaluation and PSA was used for objective evaluation. Testosterone, free testosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were used for hormonal parameters. RESULTS: Fourteen patients were eligible. The mean patient age was 75.2 years. With respect to the ECOG pain score, 5 patients scored 1 or higher, in 4 patients, the pain completely disappeared, and in 1 patient, the pain score improved from 4 to 1. The PSA level decreased significantly from 528 +/- 556 ng/ml (mean +/- SD) to 154 +/- 197 ng/ml. The DHEA level was not changed during DES-DP administration. The DHEA-S level decreased significantly from 882 +/- 430 ng/ml to 480 +/- 236 ng/ml. Testosterone and free testosterone were in the castration level before and during the treatment. Toxicity was minimal. None of the patients developed cardiovascular disorder. CONCLUSION: A moderate dose (250 mg/day) of DES-DP decreased PSA levels and relieved pain without causing serious toxicity in patients with HRPC. It is suggested that the mechanism of the DES-DP effect on the decrease in PSA and pain relief involves a decrease in DHEA-S.

Adenocarcinoma↗

Phase I-II study of neoadjuvant chemoradiotherapy followed by radical surgery in locally advanced cervical cancer.

The usefulness of neoadjuvant chemotherapy (NAC) regimens has been reported; however, the effect of NAC for advanced stages (especially stage III-IVA) is thought to be insufficient. We conducted a phase I-II study of neoadjuvant chemoradiotherapy consisting of intra-arterial (i.a.) infusion of carboplatin and intracavitary brachytherapy in patients with locally advanced cervical cancer to achieve the new NAC method. Sixteen eligible patients included those with previously untreated stage IIB, III or IVA cancer with bulky tumor. Brachytherapy using iridium-192 was performed with concurrent i.a. chemotherapy with carboplatin (200, 300 and 400 mg/m2). Treatment was repeated every 4 weeks for a total of two cycles. Both hematologic and non-hematologic toxicities were generally mild. Grade 4 hematologic toxicity was observed in 12.5% and there were no grade III or IV non-hematologic toxicities. The optimal dose of carboplatin was determined to be 400 mg/m2. Among 16 patients, six showed complete response (37.5%) and nine showed partial response (56.3%), for an overall response rate of 93.8%. All 15 responding patients underwent radical surgery with a pelvic lymphadenectomy and postoperative radiotherapy. The combination of brachytherapy and i.a. chemotherapy with carboplatin is a promising regimen for NAC in locally advanced cervical cancer.

Adenocarcinoma↗

Effect of rotavirus vaccine on Sapporo virus gastroenteritis in Finnish infants.

BACKGROUND: Sapporo-like viruses (SLVs) occur worldwide, but there is limited information about the SLV-associated gastroenteritis outside Japan. METHODS: Stool specimens from 1,432 episodes of gastroenteritis that occurred in children between 2 months and 2 years of age during a rotavirus vaccine trial (776 episodes in placebo-vaccinated and 656 in rotavirus-vaccinated infants) were examined for SLVs using a reverse transcription-PCR assay. The reverse transcription-PCR took advantage of new primers specific for Sapporo virus genetic clusters I, II and III; SV/SV82 (SV/Sapporo virus 82); SV/Lond92 (SV/ London 92); and SV/PV (Parkville virus). RESULTS: SLVs were detected in association with 132 (9.2%) of all episodes; in 80 (5.6%) episodes SLV was the only gastroenteritis virus detected. The epidemic season of SLVs peaked from March to May concurrently with rotaviruses and astroviruses and overlapping withNorwalk-like viruses. Clinically SLV gastroenteritis was characterized by a mild diarrheal disease, being sharply different from the Norwalk-like virus-associated "winter vomiting disease." Rotavirus vaccination did not have any effect on the number of SLV episodes, but the intensity and duration of SLV-associated diarrhea were reduced in rotavirus-vaccinated children compared with placebo-vaccinated children (P = 0.0008). CONCLUSIONS: SLVs are common causative agents of acute gastroenteritis in young Finnish children. SLV disease is characterized by diarrhea, which is usually mild but can be severe. By an unknown mechanism rotavirus vaccine seems to reduce the severity of SLV-associated diarrhea.

Caliciviridae Infections↗

Clinical severity of Norwalk virus and Sapporo virus gastroenteritis in children in Hokkaido, Japan.

OBJECTIVE: To clarify the clinical significance and etiologic impact of Norwalk virus (NV) and Sapporo virus (SV) in viral gastroenteritis in Japanese children. STUDY DESIGN: Two outbreaks each of NV gastroenteritis and SV gastroenteritis occurring in an infant home in Sapporo, Japan, as well as 95 hospitalized children with acute gastroenteritis were retrospectively evaluated using a 0- to 20-point clinical severity scoring system. RESULTS: The mean severity scores for NV and SV gastroenteritis outbreaks were 7.9 and 5.2, respectively, as compared with 8.4 for rotavirus A gastroenteritis that occurred in the same infant home. Among 95 hospitalized children with acute gastroenteritis, rotavirus A was detected in 47% followed by NV in 18%. SV was not found. CONCLUSION: Our data indicate that NV can cause severe gastroenteritis and is an important etiologic agent in hospitalized cases, whereas SV causes mild gastroenteritis in Japanese children.

Acute Disease↗

Molecular characterization in the VP7, VP4 and NSP4 genes of human rotavirus serotype 4 (G4) isolated in Japan and Kenya.

The VP7, VP4 and NSP4 genes of human rotavirus serotype 4 (G4) were analyzed to investigate intraserotypic variations. The techniques used included reverse transcription polymerase chain reaction with subtype specific primers, restriction fragment length polymorphism analysis and sequence analysis. Twelve isolates (nine from Japan and three from Kenya) and two standard strains (Hochi, Odelia) were G4A P[8] Wa group NSP4. A standard strain (ST3) was G4A P[6] Wa group NSP4 and a strain (VA70) was G4B P[8] Wa group NSP4. These results show G4 rotaviruses can be divided into three combinations at the moment.

Antigens, Viral↗

Apoptosis of muscle cells causes weight loss prior to impairment of DNA synthesis in tumor-bearing rabbits.

The mechanism of weight loss induced by the growth of malignant tumors is still unknown. We investigated it by focusing on apoptosis of skeletal muscle. VX2-tumor was implanted into rabbits and the apoptotic index (AI) of skeletal muscle was measured by in situ end-labeling assay. Plasma of the tumor-bearing rabbits was perfused repeatedly through non-coated charcoal resin. The AI reached 54.6% early after tumor implantation, when weight loss amounted to an 18% decrease in lean body mass (LBM) without change in muscle DNA synthesis or urinary 3-methylhistidine / creatinine ratio (3-MH / Cr). When the decrease of LBM reached 30%, DNA synthesis was decreased by 48% and 3-MH / Cr was increased by 104%, whereas AI was only 4.7%. The plasma perfusion did not prevent apoptosis in muscle, but improved LBM, DNA synthesis, and 3-MH / Cr. There may be two mechanisms of muscle depletion during the tumor growth: apoptosis in the early stage and metabolic abnormalities in muscle in the late stage.

Animals↗

Extraction of bismuth(III) with 2-bromoalkanoic acid in nondonating solvent from highly acidic aqueous solution.

The extraction behaviors of bismuth(III) with carboxylic acid (HL), which have not yet been clearly elucidated, because of the precipitation of hydroxide, were studied using the 2-bromoalkanoic acid in benzene and in hexane systems under aqueous conditions of high acidity at I = 1.0 M ((H,Li)NO3). The extraction equilibria were analyzed based on the-initial concentration of nitric acid and the concentration of bismuth(III) extracted in the organic phase. The extracted species and the logarithmic values of the extraction constant (log Kex) were found to be a single species of BiL3(HL)3 for the systems of 2-bromooctanoic acid/benzene (log Kex = -1.66) and 2-bromohexadecanoic acid/benzene (-1.58), and to be two species of BiL3(HL)4 (-1.01) and Bi3L9HL (-1.62) for the system of 2-bromooctanoic acid/hexane, where the monomer was dominant at a higher reagent concentration.

Journal Article↗

Chemical sensor based on nonlinearity: principle and application.

Novel chemical sensors based on a time-dependent nonlinear response are reviewed. The strategy is to artificially mimic information transduction in living organisms. In taste and olfaction, information of chemical structure and concentration is transformed into nervous impulses in the nervous cell, i.e., time-dependent multi-dimensional information. Because the excitation and pulse generation in the nervous cell are typically nonlinear phenomena, it may be worthwhile to utilize the nonlinearity as the multi-dimensional information for molecular recognition. The principle of a "nonlinear" sensor is that a sinusoidal modulation is applied to a system, and the output signal is analyzed. The output signal of the sensor is characteristically deformed from the sinusoidal input depending on the chemical structure and concentration of the chemical stimuli. The characteristic nonlinear responses to chemical stimuli are discussed in relation to the kinetics of chemical compounds on the sensor surface. As a practical application, we introduced electrochemical sensors based on the differential capacitance, semiconductor gas sensors under the application of sinusoidal temperature or diffusion change, and a chemical sensor based on the spatio-temporal information. We demonstrated that mutli-dimensional information based on nonlinearity can provide quite useful information for the analysis of chemical species, even in the presence of another analyte or an interference with a single detector.

Artificial Organs↗