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Biomedical subjects

M Nonaka

Publications and source records attributed to M Nonaka.

At least 127 records · Page 7Linked to original sources
PubMed1998

Cross polarization for 1H NMR image contrast in solids

A novel 1H imaging method for solids, yielding images reflecting 1H-13C dipolar interactions through cross relaxation time TIS, is presented. Phase-alternating multiple-contact cross polarization (PAMC CP) was incorporated into the magic-echo frequency-encoding imaging scheme; the PAMC CP sequence may partly but efficiently destroy the initial 1H magnetization depending on the TIS values. A theory describing the effects of the PAMC CP sequence was developed, which was used for the assessment of the sequence as well as the analysis for the experimental results. It was demonstrated that the TIS-weighted 1H image and the TIS mapping for a phantom, constituted of adamantane and ferrocene, can distinguish these compounds clearly. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

A new repetitive sequence uniquely present in the decay-accelerating factor genes.

The decay-accelerating factor (DAF, CD55) protects cells from autologous complement attack on self cell membranes. We have previously reported that the seventh exon encoding the serine/threonine-rich(S/T)-abc region of the guinea pig DAF gene is composed of five homologous repeats of about 51 base pairs, and that differential usage of these repeats produces the various lengths observed in the S/T region of guinea pig DAF. In this study, we found that the seventh intron of the guinea pig DAF gene was wholly composed of 18 tandem repeats homologous to the repeating unit of the S/T-abc exon. This type of repetitive structure, although the number of repeats was variable, was also found in the corresponding exons and introns of all DAF genes of other species so far tested including human and seven other primates and mouse, in which alternative splicing in this region has not been found. This suggested that generation of the repetitive sequences spanning the exon and intron regions had occurred before the diversification of these species. In addition, all the intron sequences of the tested DAF genes had no stop codon when they were presumably translated in the same reading frame as the seventh and eighth exons, except for that of one of two duplicated mouse DAF genes. These findings and significant interspecies identities of the intron sequence suggest that the intron sequence conceivably could be translated in some tissues and/or in some stages of development although to date we have not yet succeeded in detecting mRNA for this region.

Amino Acid Sequence↗
PubMed1998

Changes in lung lobar volume and bronchial deformity after right upper lobectomy.

To explore the anatomical repositioning of the middle lobe following right upper (RU) lobectomy, we measured the lobar volumes of the lung and the branching angles of the airway, and defined their changes after RU lobectomy in a rabbit model. Groups A1 (n = 10) and A2 (n = 10) were control groups and groups B1 (n = 10) and B2 (n = 10) underwent RU lobectomy. Casting material was introduced into the airway and a heart-lung bloc was removed form the thoracic cavity in all groups. In groups A1 and B1, the volume of each lobe of the bilateral lungs was measured, while in groups A2 and B2, bronchial casts were made and the branching angles of the airway were measured. The volume ratio of the right upper lobe (RUL) to the total lung was 12.0 +/- 0.4% in group A1; however, after RU lobectomy, the volume ratio of the right middle lobe (RML) to the total lung increased from 8.7 +/- 0.6% in group A1 to 13.5 +/- 0.8% in group B1. The volume of the left lung also increased from 43.0 +/- 0.5% in group A1 to 48.8 +/- 1.1% in group B1. The angle between the truncus intermedius and the RML bronchus was significantly smaller in group B2, at 109.0 +/- 3.5 degrees, than in group A2, in which it was 138.5 +/- 1.7 degrees. The angle between the RML bronchus and the coronal plane was 57.5 +/- 2.5 degrees in group A2 and 33.5 +/- 3.3 degrees in group B2. Our method of measuring the bronchial branching angle subsequent to RU lobectomy proved useful to illustrate postoperative positional changes and expansion of the remaining lobes.

Animals↗
PubMed1998

Metastatic meningeal hemangiopericytoma of thoracic spine.

We report a case of metastatic meningeal hemangiopericytoma in thoracic spine. A 49-year-old female having a history of tentorial hemangiopericytoma first found 116 months before was admitted to our hospital with acute onset of paraplegia. Magnetic resonance image revealed a tumor invading the left lamina and pedicle of the 8th thoracic vertebra, and compressing the dural sac severely. After subtotal removal of the tumor, the patient showed rapid neurological improvement. The histological findings were characteristic of hemangiopericytoma. Because extradural metastases of meningeal hemangiopericytoma occur long after previous treatment in unexpected sites especially in skeletal system, repeated bone scintigraphy is essential.

Adult↗
PubMed1998

Complement-related serine proteases in tunicates and vertebrates.

Serum mannose-binding lectin binds to pathogens in association with a serine protease termed MASP, and in this form, plays a crucial role in innate immunity by activating complement in a manner similar to activation via the classical pathway. MASP, C1r and C1s belong to the same family of serine proteases. In addition to its presence in advanced species, MASP also exists in primitive life forms such as tunicates and may be an evolutionary prototype of this family.

Animals↗
PubMed1998

Intercellular adhesion molecule-1 expression in the inner ear of rats following secondary immune reaction in the endolymphatic sac.

An immunological aetiology for inner ear diseases has long been proposed. The endolymphatic sac (ES) is the only immunoprivileged site in the inner ear with a resident population of immunocompetent cells. By keyhole limpet hemocyanin (KLH) challenge into the ES of systemically pre-immunized guinea pigs, we previously demonstrated an infiltration of inflammatory cells into the perilymphatic space of the cochlea. In order to understand the mechanisms involved in the recruitment of immunocompetent cells into the inner ear, and their relation to the development of endolymphatic hydrops (EH), we investigated the expression and time-kinetics of intercellular adhesion molecule 1 (ICAM-1) in the inner ear of systemically pre-immunized rats after antigen (KLH) challenge into the ES, its relation to cell infiltration in the cochlea and subsequent development of EH. By immunohistochemistry, strong ICAM-1 expression was detected in the spiral ligament, suprastrial region, spiral prominence, spiral modiolar veins, spiral collecting venules, surface membrane of the perilymphatic compartment, perilymphatic space and ES of immunized rats, but not of control rats. ICAM-1 expression was detected at 5-6 h, peaked at 10-15 h, and gradually reduced by 2 weeks. Cell infiltration into the cochlea started at 6-12 h and peaked at day one. By 6 h, 50% of challenged rats developed EH. This figure rose to 70% at 12 h, and then gradually reduced. However, immunoreactivity for KLH (antigen) was only detected in the ES. These results emphasize that the sac is the central immunological organ of the inner ear, and suggest that ICAM-1 may play a pivotal role in the aetiology of immune-mediated inner ear diseases through the recruitment of immunocompetent cells into the inner ear and subsequent development of EH.

Animals↗
PubMed1998

Effect of roxithromycin on IL-8 synthesis and proliferation of nasal polyp fibroblasts.

Although several studies have demonstrated that low-dose, long-term 14-member macrolides (erythromycin (EM), roxithromycin (RXM), clarithromycin (CAM)) are effective in the treatment of chronic airway diseases like chronic sinusitis and diffuse panbronchiolitis (DPB), the mechanism of action of these drugs is not yet clear. Both these airway diseases are associated with an increase in the proliferation of fibroblasts. Moreover, fibroblasts are also an important source of proinflammatory cytokines such as interleukin-8 (IL-8), that play an important role in the pathogenesis of nasal polyps. Therefore, using primary fibroblast lines derived from nasal polyps, we investigated the effect of RXM on the synthesis of IL-8 and proliferation of nasal polyp fibroblasts (NPF). These fibroblasts were either treated with lipopolysaccharide (LPS) and RXM for 24 h, or pre-incubated with RXM for 24 h and then treated with LPS and RXM for 24 h. The level of IL-8 mRNA in NPF was analysed by reverse transcriptase-polymerase chain (RT-PCR) and the level of IL-8 in culture supernatants was measured by ELISA. Next, the proliferative capacity of NPF after treatment with RXM was analysed by cell counting and 3H-thymidine uptake. RXM had no effect on LPS-induced IL-8 synthesis by NPF. On the other hand, RXM suppressed the proliferation of NPF in a dose-dependent manner. These findings suggest that, although RXM cannot directly inhibit the synthesis of IL-8, it probably reduces IL-8 production by inhibiting the proliferation of NPF.

Anti-Bacterial Agents↗
PubMed1998

Dihydropyrimidinase deficiency: structural organization, chromosomal localization, and mutation analysis of the human dihydropyrimidinase gene.

Dihydropyrimidinase (DHP) deficiency (MIM 222748) is characterized by dihydropyrimidinuria and is associated with a variable clinical phenotype. This disease might be associated with a risk of 5-fluorouracil toxicity, although no cases have been reported. We present here both the molecular characterization of the human DHP gene and, for the first time, the mutations causing DHP deficiency. The human DHP gene spans >80 kb and consists of 10 exons. It has been assigned to 8q22, by FISH. We performed mutation analysis of genomic DNA in one symptomatic and five asymptomatic individuals presenting with dihydropyrimidinuria. We identified one frameshift mutation and five missense mutations. Two related Japanese adult subjects were homozygous for the Q334R substitution, whereas two other, unrelated Japanese infant subjects were heterozygous for the same mutation, but this mutation is not common in the Japanese population. A Caucasian pediatric patient exhibiting epileptic attacks, dysmorphic features, and severe developmental delay was homozygous for W360R. Using a eukaryotic expression system, we showed that all mutations reduced enzyme activity significantly, indicating that these are crucial DHP deficiency-causing mutations. There was no significant difference, in residual activity, between mutations observed in the symptomatic and those observed in the asymptomatic individuals.

Adult↗
PubMed1998

Bowenoid papulosis showing polyclonal nature.

Bowenoid papulosis (BP) is characterized clinically by its benign-looking appearance and histologically by the features of high grade squamous intraepithelial lesions (SILs). The external genitalia of young people is a common site of occurrence, and most of the lesions undergo resolution by local treatments or even spontaneously. A strong association between BP and high risk types of human papillomavirus (HPV), especially HPV 16, has been reported and the incorporation of BP into the SIL category is generally accepted, but controversy still exists as to the true nature of BP. We analyzed the clonality of BP lesions occurring on both sides of the vulva of a 15-year-old girl. DNA was subjected to a polymerase chain reaction-based clonal analysis using the highly informative androgen receptor gene (HUMARA) with a nonisotopic modification. The clonal analysis of each BP lesion showed a random X-chromosome inactivation pattern, indicating a polyclonal nature of this disorder. Although monoclonal proliferation of vulvar SIL was recently reported, this is the first report of the polyclonality in a type of SIL diagnosed as BP, supporting a clinicopathologic heterogeneity in SIL of the vulva.

Adolescent↗
PubMed1998

Abnormalities of electrocardiographic P wave morphology and their relation to electrophysiological parameters of the atrium in patients with sick sinus syndrome.

We examined the incidence of long P wave duration in lead II and increased P terminal force in lead V1 (PTFV1), and their relationship to electrophysiological findings of atrial muscle in 34 patients with sick sinus syndrome (SSS). Patients were divided into three groups: Group I, consisting of 20 patients with various cardiac arrhythmias other than SSS and paroxysmal atrial fibrillation (PAF) who served as controls; Group II, consisting of 18 patients with SSS but without PAF; and Group III consisted of 16 patients with SSS and PAF. P wave duration was significantly longer in Group III (122 +/- 11 ms, mean +/- SD, P < 0.0001) and Group II (111 +/- 15 ms, P < 0.002) than in Group I (98 +/- 10 ms). PTFV1 was greater in Group III (0.052 +/- 0.025 ms) than in Group I (0.028 +/- 0.011 ms, P < 0.05). P wave duration and PTFV1 had significantly and/or borderline correlations with longest duration of right atrial electrograms (r = 0.84, P < 0.0001 and 0.47, P < 0.02, respectively), maximal number of fragmented deflections of atrial electrograms (r = 0.69, P < 0.0001 and r = 0.51, P < 0.02, respectively), repetitive atrial firing zone (RAFZ) (r = 0.81, P < 0.0001 and 0.48, P < 0.05, respectively) and fragmented atrial activity zone (FAAZ)(r = 0.53, P < 0.01 and r = 0.45, P = 0.06, respectively). We concluded that long P wave duration and increased PTFV1 are electrocardiographic indicators for coexistence of electrophysiological abnormalities in the atria in SSS without recognizable heart disease.

Adult↗
PubMed1998

Molecular genetics of the complement C3 convertases in lower vertebrates.

Evolution of the two gene families of the complement system involved in the formation of the C3 convertases, B/C2 and C3/C4/C5, was studied at the cDNA level in lower vertebrates. Cyclostomes, the most primitive extant vertebrates, seem to possess only one member each of these families, indicating that gene duplication between B and C2 or among C3, C4 and C5 occurred in the lineage of jawed vertebrates. Typical C3 and C4 cDNAs were identified in both amphibian (Xenopus) and teleost (medaka fish), locating the C3/C4 gene duplication before the divergence of ray-finned fish and lobe-finned fish. On the other hand, typical B cDNA was identified in Xenopus, whereas teleost counterparts from three species all showed intermediate character between B and C2, suggesting the possibility that the B/C2 gene duplication occurred in the tetrapod lineage. Genetic linkage between these two family genes within the MHC was observed in Xenopus but not in medaka fish.

Animals↗
PubMed1998

Effect of dietary fats and sesamin on the lipid metabolism and immune function of Sprague-Dawley rats.

We examined the effect of three dietary fats, safflower oil (SAF) rich in linoleic acid, borage oil (BOR) rich in gamma-linolenic acid, and perilla oil (PER) rich in alpha-linolenic acid, on the lipid metabolism, and chemical mediator and immunoglobulin levels in Sprague-Dawley rats, as well as the dietary effect of sesame-derived antioxidative sesamin. The serum cholesterol, phospholipid, triglyceride, prostaglandin E2 level and splenic leukotriene B4 level were lower in the rats fed on BOR or PER than in those fed on SAF. SES feeding suppressed the expression of the lipid-decreasing effect of BOR, but not in the rats fed on PER. In respect of the fatty acid composition of the liver and spleen, PER feeding gave a lower arachidonic acid level, and higher eicosapentaenoic and docosahexaenoic acid levels than SAF feeding did, while the effect of BOR feeding was marginal. The effect of SES feeding on fatty acid composition was much smaller than that of dietary fats. In respect of immunoglobulin production, PER + SES feeding gave the lowest IgE productivity in the mesenteric lymph node lymphocytes. These results suggest that PER feeding regulated lipid metabolism and exerted an anti-allergic effect by a different mechanism from that with BOR feeding.

Animals↗
PubMed1998

[A successful case of minimally invasive direct coronary artery bypass (MIDCAB) followed by PTCA].

A 70-year-old man who developed angina pectoris underwent cardiac catheterization, which showed total occlusion of the left anterior descending coronary artery (LAD), associated with 75% stenosis of the right coronary artery (RCA) and 90% stenosis of the small circumflex coronary artery (CX). The LAD received good collateral flow from the RCA. The patient was scheduled to undergo the MIDCAB for the LAD using the internal thoracic artery (ITA), combined with percutaneous transluminal coronary angioplasty (PTCA) for the RCA subsequently. A left anterior submammarian skin incision of 10 cm in length was made. The fifth costal cartilage was removed. The left ITA was directly harvested from the chest wall from the 4th to 7th intercostal space, and was anastomosed to the midportion of the LAD without cardiopulmonary bypass. The patient was quickly recovered after the operation. On the 8th postoperative day, the patient successfully underwent the PTCA for the RCA after the ITA-LAD graft had been verified to be patent. The MIDCAB could be indicated for multivessel coronary disease in conjunction with the PTCA.

Aged↗
PubMed1998

Identification of novel mutations in the dihydropyrimidine dehydrogenase gene in a Japanese patient with 5-fluorouracil toxicity.

5-Fluorouracil (5-FU) is used widely in the treatment of several common neoplasms. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-FU. Several recent studies have described a pharmacogenetic disorder in which cancer patients with decreased DPD activity develop life-threatening toxicity following exposure to 5-FU. We reported recently the first Japanese case of decreased DPD activity accompanied by severe 5-FU toxicity. The present study describes the results of molecular analysis of this patient and her family, in which three novel mutations (Arg21Gln, Val335Leu, and Glu386Ter) of the gene coding for DPD were identified. We also revealed that Arg21Gln and Glu386Ter are on the same allele and that Val335Leu is on the other allele, on the basis of analysis of the family genome. Expression analysis in Escherichia coli showed that Val335Leu and Glu386Ter led to mutant DPD protein with significant loss of enzymatic activity and no activity, respectively. The Arg21Gln mutation, however, resulted in no decrease in enzymatic activity compared with the wild type. The present data represent the first molecular genetic analysis of DPD deficiency accompanied by severe 5-FU toxicity in a Japanese patient.

Antimetabolites, Antineoplastic↗
PubMed1997

Evolution of proteasome subunits delta and LMP2: complementary DNA cloning and linkage analysis with MHC in lower vertebrates.

The class II region of the mammalian MHC harbors two proteasome subunit genes, LMP2 and LMP7. These genes are induced by IFN-gamma, and their products are incorporated into proteasomes substituting for their closest relatives, the delta and X subunits, respectively. This substitution is believed to change the proteolytic specificity of proteasomes, making it more suitable for generation of peptides to be presented by class I molecules. To elucidate the phylogenetic origin of LMP2 and the linkage of its gene with the MHC, reverse transcriptase-PCR amplification of Xenopus laevis and lamprey liver mRNA was performed with primers designed to amplify both the mammalian LMP2 and delta sequences. Both LMP2 and delta were amplified from X. laevis, whereas only delta was amplified from lamprey, suggesting that delta/LMP2 gene duplication occurred after divergence of cyclostomes but before divergence of amphibians. The linkage between the LMP2 gene and the MHC was observed in a diploid Xenopus species, Xenopus tropicalis, but not in a tetraploid species, X. laevis, indicating that this linkage was established before the divergence of amphibian from higher vertebrates, but that this linkage was lost in X. laevis, probably by a gene reorganization accompanying the tetraploidization. The X. laevis LMP2 and LMP7 mRNA showed a similar tissue distribution, indicating that the genetic linkage is not required for apparently coordinated tissue-specific expression of these genes. Sequence and linkage analyses suggest that LMP2 may not play as vital a role as LMP7 in Ag presentation.

Amino Acid Sequence↗
PubMed1997

Ancient origin of the complement lectin pathway revealed by molecular cloning of mannan binding protein-associated serine protease from a urochordate, the Japanese ascidian, Halocynthia roretzi.

Recent identification of a C3-like gene in sea urchins revealed the presence of a complement system in invertebrates. To elucidate further the components and function of the pre-vertebrate complement system, we attempted to isolate an ascidian (urochordata) C3 convertase. After identification of C3 cDNA from Halocynthia roretzi, a Japanese ascidian, reverse transcriptase-PCR amplification of hepatopancreas RNA was performed using primers encoding highly conserved amino acid sequences of the vertebrate Bf and C2 serine protease domain. Two candidate sequences were identified, and the corresponding cDNA clones were isolated from a hepatopancreas library. Surprisingly, neither clone is related to Bf/C2 but rather share the same domain structure of mammalian C1r/C1s/MASP (mannan binding protein-associated serine protease), and are more related evolutionarily to mammalian MASP than to mammalian C1r or C1s. The identification of the tunicate MASP clones, amplified with primers designed to amplify Bf or C2, suggests that the lectin pathway antedated the classical and alternative pathways of complement activation.

Amino Acid Sequence↗