Biomedical subjects

M Nonaka

Publications and source records attributed to M Nonaka.

At least 19 recordsLinked to original sources

PubMed1999

Opsonic complement component C3 in the solitary ascidian, Halocynthia roretzi.

The recent identification of two mannose-binding lectin-associated serine protease clones from Halocynthia roretzi, an ascidian, suggested the presence of a complement system in urochordates. To elucidate the structure and function of this possibly primitive complement system, we have isolated cDNA clones for ascidian C3 (AsC3) and purified AsC3 protein from body fluid. The deduced primary structure of AsC3 shows overall similarity to mammalian C3, including a typical thioester site with the His residue required for nucleophilic activation of the thioester. AsC3 has a two-subunit chain structure, and the alpha-chain is cleaved at a specific site near to the N terminus upon activation. Ascidian body fluid contains an opsonic activity which enhances phagocytosis of yeast by ascidian blood cells, and Ab against AsC3 inhibits this opsonic activity. These results indicate that the complement system played a pivotal role in innate immunity by enhancing phagocytosis before the emergence of the vertebrates and well ahead of the establishment of adaptive immunity, which is believed to have occurred at about the time of the appearance of cartilaginous fish.

Amino Acid Sequence↗

PubMed1999

Platelets as participants in hyperacute guinea pig-to-rat lung xenorejection.

It is well known that xenotransplantation leads to immediate graft dysfunction. This study was designed to specifically examine the role of platelets in mediating lung hyperacute xenorejection (HXR) in a guinea pig-to-rat model. A total of 18 lungs were perfused with blood using an ex vivo apparatus. The animals were divided into the following four groups: a CE group comprising circuit only with rat blood; a SYN group comprising rat lungs and blood; a XE group comprising guinea pig lungs and rat blood; and an SH group comprising guinea pig lungs and rat blood with sarpogrelate hydrochloride, a suppressor of platelet aggregation. The platelet and serotonin in the blood were lower and the wet/dry weight ratio of the lung (W/D) in the XE group were higher than those in the SYN group after perfusion. The platelet count was higher, but the serotonin and W/D were lower in the SH group than in the XE group. These results suggest that platelets strongly affect HXR. Thus, the administration of drugs to suppress platelet aggregation would reduce xenotransplanted lung edema.

Animals↗

PubMed1999

Effects of initial low flow reperfusion and surfactant administration on the viability of perfused cadaveric rat lungs.

To expand the cadaveric lung donor pool, protecting the endothelium and alveoli from warm ischemia and reperfusion injury is important. The effects of initial low flow reperfusion and surfactant administration were studied in non-heart-beating donor lungs. The rat heart-lung bloc was excised immediately (group 1) or 30 min (groups 2-4) after euthanasia (n = 6 in each group). The graft was ventilated and reperfused (50 ml/min) immediately after excision for 1 h in groups 1 and 2. In groups 3 and 4, the reperfusion flow rate was increased gradually to 50 ml/min, while ensuring that the pulmonary arterial pressure did not exceed 40 mmHg. Then the graft was reperfused for 1 h. Surfactant was introduced into the airway in group 4 before reperfusion. Airway pressure (AWP) and pulmonary arterial pressure were monitored during reperfusion. After reperfusion, the wet/dry weight ratio (W/D) of the right lung was calculated, and histologic examination using trypan blue staining of the left lung was performed. In group 2, lung failure appeared in all animals during reperfusion. In group 3, although all lungs were reperfused for 1 h, AWP and W/D were higher than in group 1. In group 4, AWP and W/D were lower than in group 3. Histologic examination showed that surfactant administration had attenuated the alveolar cell death. To avoid damage caused by high pulmonary arterial pressure associated with graft reperfusion, iniital low flow reperfusion was beneficial in cadaveric lungs. Surfactant administration before reperfusion was effective in preventing pulmonary edema.

Animals↗

PubMed1999

Surgical treatment of internal carotid artery anterior wall aneurysm with extravasation during angiography--case report.

A 54-year-old female presented subarachnoid hemorrhage from an aneurysm arising from the anterior (dorsal) wall of the internal carotid artery (ICA). During four-vessel angiography, an extravasated saccular pooling of contrast medium emerged in the suprasellar area unrelated to any arterial branch. The saccular pooling was visualized in the arterial phase and cleared in the venophase during every contrast medium injection. We suspected that the extravasated pooling was surrounded by hard clot but communicated with the artery. Direct surgery was performed but major premature bleeding occurred during the microsurgical procedure. After temporary clipping, an opening of the anterior (dorsal) wall of the ICA was found without apparent aneurysm wall. The vessel wall was sutured with nylon thread. The total occlusion time of the ICA was about 50 minutes. Follow-up angiography demonstrated good patency of the ICA. About 2 years after the operation, the patient was able to walk with a stick and to communicate freely through speech, although left hemiparesis and left homonymous hemianopsia persisted. The outcome suggests our treatment strategy was not optimal, but suture of the ICA wall is one of the therapeutic choices when premature rupture occurs in the operation.

Aneurysm, Ruptured↗

PubMed1999

[Effects of coronary artery bypass surgery on the stunned and hibernating myocardium in the cases with depressed left ventricular function].

Chronic left ventricular (LV) dysfunction may result from irreversible damage (cell death), stunned myocardium (ST), or hibernating myocardium (HB). However, both of ST and HB are expected to be reversible. In this report, the effects of coronary artery bypass grafting on the regions of ST and HB were evaluated in 37 patients with less than 40% of LV ejection fraction. The patients were divided into two groups. Group I consisted of the patients whose postoperative LV ejection fraction rose by more than 10% compared to the preoperative value. Group II included the remaining patients with no significant improvement. After successful revascularization, 61% of HB changed to ST and 52% of ST to normal in group I. These changes were significant in comparison with group II because 48% of HB and 83% of ST in group II remained unchanged. Immediate or rapid recovery of HB hardly occurred in both of the groups. To recover normal function, HB may pass through a stage of ST on reperfusion. On the other hand, it is difficult to determine whether HB and ST with no significant changes after reperfusion are irreversibly damaged or reversible and take time to return to normal.

Aged↗

PubMed1999

[ASO as a risk factor of emergency CABG].

The presence of lower extremity arterial occlusive disease (arteriosus sclerosis obliterance of lower extremity) is an important risk factor for patients undergoing emergency coronary artery bypass operations. Those patients had higher mortality and morbidity rates related to the complications of intraaortic balloon pumps (IABP). If lower extremity ischemia is observed, rapid procedures such as removal of the IABP with or without thrombectomy and femorofemoral crossover interposition of a graft should be performed.

Aged↗

PubMed1998

Two diverged complement factor B/C2-like cDNA sequences from a teleost, the common carp (Cyprinus carpio).

Mammalian complement components factor B and C2 act as proteolytic subunits of the C3 convertases in the alternative and the classical activation pathways, respectively, and are believed to have diverged from a common ancestor by gene duplication. However, it is unclear when the B/C2 duplication occurred. Here, we describe two diverged B/C2-like cDNA clones (B/C2-A and B/C2-B) isolated from a bony fish, the common carp (Cyprinus carpio). B/C2-A shares the same domain structure as the factor B and C2 complement components of vertebrates reported so far and shows a close similarity to zebrafish B and medaka fish B/C2. These teleost sequences show almost the same degree of similarity to C2 and B of higher vertebrates. In contrast, B/C2-B has a novel structural feature in that it contains four short consensus repeat modules and does not have a close relative upon phylogenetic analysis. Northern blotting revealed the presence of two transcripts with different sizes for both the B/C2-A and B/C2-B in the hepatopancreas of the carp. Southern blotting suggested the presence of multiple genes for B/C2-A and a single gene for B/C2-B. Although structural features of B/C2-B are slightly more C2-like than B-like, B/C2-B has a crucial amino acid substitution in the serine protease domain, which makes it unlikely that B/C2-B functions as a C3 convertase. A possible phylogenetic relationship between the two carp sequences and mammalian C2 and B is discussed.

Amino Acid Sequence↗

PubMed1998

Two lineages of mannose-binding lectin-associated serine protease (MASP) in vertebrates.

Mannose-binding lectin-associated serine protease (MASP) is a newly identified member of the serine protease superfamily. MASP is involved in host defense against pathogens through a novel system of complement activation, designated the lectin pathway. To elucidate the origin of the lectin pathway and the molecular evolution of MASP, we cloned six MASP cDNAs from five vertebrate species going from mammal to cyclostome. An alignment of the amino acid sequences deduced from the cDNAs revealed the presence of two different lineages of the MASP gene. This classification was supported by the precise correlation with two types of exon organization for the protease domain. One of the two lineages is unique in that a single exon encodes the protease domain, unlike most other serine proteases. All members of this group, termed the AGY type, have an AGY codon at the active site serine. A phylogenetic tree suggests that the AGY type diverged from another lineage, termed the TCN type, before the emergence of primitive vertebrates. Furthermore, the presence of MASP or MASP-like sequences in most vertebrate species suggests that the lectin pathway functions extensively in vertebrates and that its origin is traced back to the invertebrate stage.

Amino Acid Sequence↗

PubMed1998

Changes in brain organic osmolytes in experimental cerebral ischemia.

The cell volume is regulated not only by inorganic ions, but also by organic osmolytes, such as amino acids, methylamines, and polyhydric alcohols (polyols). Using proton nuclear magnetic resonance spectroscopy (1H-NMR), we measured the tissue concentrations of amino acids (alanine, aspartate, gamma-aminobutyric acid (GABA), glutamate, glutamine, N-acetyl-aspartate (NAA), taurine), methylamines (glycerophosphorylcholine (GPC), creatine+phosphocreatine (total creatine, tCr)), and polyols (myo-inositol) in the rat brain after middle cerebral artery occlusion (incomplete focal ischemia) or after decapitation (complete global ischemia). The total osmolytes expressed as a sum of total amino acids, total methylamines, and total polyols were significantly decreased at 24 h of focal ischemia (58.7% of control value, P=0.0025) whereas they were not changed following decapitation. The water content was increased from control value of 77.9%-84.1% after focal ischemia (P<0.0001) but not after decapitation. These results suggest that the brain organic osmolytes are involved in the process of edema formation following focal cerebral ischemia. Further elucidation of the cellular mechanisms regulating these organic osmolytes in cerebral ischemia may promote greater understanding of the pathophysiology involved in the evolution of brain edema.

Alanine↗

PubMed1998

Increased transcription of glutamate-aspartate transporter (GLAST/GluT-1) mRNA following kainic acid-induced limbic seizure.

Expression of mRNA for glutamate-aspartate transporter (GLAST/GluT-1/EAAT1) was studied in the brain of the rat which presented recurrent limbic seizure following systemic administration of kainic acid (KA) by in situ hybridization and Northern blot analysis. The expression of GLAST mRNA was markedly increased after 12 h and peaked after 48 h in animals which demonstrated limbic seizure. The induction of the mRNA were observed in the small non-neuronal cells in the hippocampus, especially around CA3 region and hilus. In contrast, there was no change in GLAST mRNA levels in KA injected seizure-free animals. These findings suggest that GLAST mRNA is induced by seizure and increased extracellular glutamate levels during seizure may be important for induction of GLAST mRNA.

ATP-Binding Cassette Transporters↗

PubMed1998

Expression of MHC class Ia and class Ib during ontogeny: high expression in epithelia and coregulation of class Ia and lmp7 genes.

The amphibian Xenopus permits the examination of immune responses in a species that progresses through two distinct lives, tadpole and adult, in which animals are free-living and immunocompetent. MHC gene expression as well as general features of the immune system change profoundly at metamorphosis. In this study gene expression of class Ia, class Ib, and the immune proteasome component lmp7 was investigated by Northern blotting at all stages of development. Class Ia genes are expressed in most adult tissues, with highest levels in intestine. Class Ib genes are expressed at lower levels, and their tissue distribution is somewhat more restricted than that of class Ia. Consistent with the idea that particular class Ib isotypes can perform distinct functions, preferential expression of class Ib genes is found in some tissues, with one family being expressed exclusively in epithelia. The onset of MHC expression is not simultaneous in all tissues: class Ia transcripts are first present in tadpole lung, gill, and intestine, organs with epithelial surfaces in contact with the environment. In every tissue except colon and muscle, class Ia expression increases markedly after metamorphosis. Interestingly, expression of the MHC-linked proteasome component lmp7 mirrored class Ia expression, while the constitutive lmp7 homologue X was expressed ubiquitously at all stages. Class Ib transcripts were never detected before metamorphosis, suggesting that the Xenopus class Ib proteins identified to date do not subserve class Ia functions in tadpole life.

Animals↗

PubMed1998

Functional differences among multiple isoforms of guinea pig decay-accelerating factor.

Decay-accelerating factor (DAF, CD55) is a membrane inhibitor that protects host cells from the autologous C-mediated attack. The guinea pig homologue of DAF consists of multiple isoforms generated by alternative splicing from a single copy gene. These isoforms are mainly comprised of a glycosylphosphatidylinositol (GPI)-anchored form and a transmembrane form (TM) that is not present in human DAF. Both forms occur in at least three variations that differ in the length of the Ser/Thr-rich region (termed ST-a, ST-ab, and ST-abc). We have transfected cDNAs of the six major isoforms into Chinese hamster ovary cells, and their functional differences were evaluated in inhibition of C-mediated cytolysis and C3 deposition, using the transfectants expressing DAF at the same level on cell membranes. The degree of inhibition in both the classical and alternative pathways differed according to the length of the ST region in the order of abc > ab > a in both GPI and TM forms. When GPI and TM forms were compared, those with the ab or abc variation exhibited almost the same activity, whereas a-TM was less efficient than a-GPI. Although several isoforms are expressed constitutively in most of tissues, spermatozoa preferentially express the abc-GPI isoform, suggesting that this isoform offers effective protection to spermatozoa in the female genital tract.

Animals↗

PubMed1998

Post-meiotic expression of the mouse dihydropyrimidinase-related protein 3 (DRP-3) gene during spermiogenesis.

The dihydropyrimidinase-related protein (DRP) family, originally identified in humans by their homology to dihydropyrimidinase, contains at least four members. Genes of this family, and their counterparts in other mammals and chickens, are expressed mainly in fetal and neonatal brain, suggesting that the encoded proteins have a physiological role in the development of the central nervous system. In addition, the DRP-3 gene is expressed in testis as a shorter mRNA than the brain form. As a first step in understanding the extra-neuronal function of DRP-3, the structure and expression of testis DRP-3 were examined. Testis DRP-3 cDNA showed the same sequence as brain DRP-3 cDNA, except for the 5'-terminal end, which encodes a 5'-untranslated region and the 11 N-terminal amino acid residues, indicating that the two forms of DRP-3 mRNA were transcribed from a single copy gene. Northern blotting analysis detected DRP-3 mRNA in 30-, 40- and 70-day-old, but not in 10- and 20-day-old testes. In situ hybridization analysis indicated that the expression of DRP-3 in testis is restricted to post-meiotic round spermatids. This is the first report of the expression of DRP genes in extra-neuronal cells.

Amino Acid Sequence↗

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↗