Biomedical subjects

H Ninomiya

Publications and source records attributed to H Ninomiya.

At least 199 records · Page 11Linked to original sources

PubMed1995

[A case report of surgical repair for distal aortic arch aneurysm with abdominal aortic aneurysm].

A 77-year-old female was referred to our hospital with hoarseness and an abnormal shadow on her chest X ray film. Computed tomography and aortography revealed aneurysms of the distal aortic arch and the infrarenal abdominal aorta. Total aortic arch replacement was performed successfully on the patient, utilizing hypothermic selective cerebral perfusion. The operation employed three technical characteristics for avoidance of cerebral complication. Those were as follows: First, total aortic arch replacement was performed instead of distal aortic arch replacement because of severe sclerosis of the proximal aortic arch. Secondly, to prevent cerebral embolism due to the thrombi on the wall of the abdominal aortic aneurysm, an arterial cannula for cardiopulmonary bypass was inserted in the ascending aorta initially and after completion of the distal anastomosis, it was placed on the graft. Thirdly, the so called "non clamping technique" operation was employed because clamping onto the sclerotic arteries might have caused cerebral embolism. There was no cerebral complication and the postoperative course was satisfactory.

Aged↗

PubMed1995

[CD5-negative B-cell chronic lymphocytic leukemia (B-CLL) associated with massive splenomegaly and without lymphadenopathy].

A 39-year-old male was referred to our hospital in June, 1993, because of leukocytosis. Physical examinations showed massive splenomegaly without any lymphadenopathy. The white blood cell count was 13,800/microliters with 87% morphologically mature lymphocytes. Bone marrow aspirate revealed hypercellularity with 67% lymphocytes morphologically similar to peripheral lymphocytes. The lymphocytes displayed monoclonal rearrangements of immunoglobulin genes and the phenotype of CD5-CD19+CD20+ CD21+ and Smlg+. Splenectomy was effective against neutropenia and thromboytopenia. The clinical and laboratory findings of this case were unusual compared to those of typical B-CLL in massive splenomegaly, no lymphadenopathy and CD5-phenotype, suggesting the heterogeneity of B-CLL.

Adult↗

PubMed1995

Distinct roles of second and third intracellular loops of human endothelin receptors in the selective activation of G alpha s/G alpha i.

Endothelin-1 (ET-1) stimulated cAMP formation in Chinese hamster ovary cells stably expressing human wild-type ET(A) (CHO/hET(A) cells) and inhibited the formation in cells expressing human wild-type ETB (CHO/hETB cells), suggesting a selective coupling of hET(A) and hETB with G alpha s and G alpha i, respectively. To find out the receptor domain(s) that determined the selective coupling, a series of chimeric receptors between hET(A) and hETB were expressed on CHO cells and the effect of ET-1 on cAMP formation in each cell line was tested. hET(A) with the replacement of the second and/or third intracellular loop (ICLII and/or III) to the corresponding region(s) of hETB failed to transmit the stimulatory effect of ET-1. hETB with the replacement of ICLIII to the corresponding region of hET(A) failed to transmit the inhibitory effect of ET-1. A chimeric receptor with ICLII of hETB and with ICLIII of hET(A) failed to transmit either effect. These results indicated the roles of ICLII and III of hETR as major determinants of the selective coupling of hET(A)/hETB with G alpha s/G alpha i, respectively.

Animals↗

PubMed1995

Functional coupling of ETA receptor with Ca(2+)-permeable nonselective cation channel in mouse fibroblasts and rabbit aortic smooth-muscle cells.

Endothelin-1 (ET-1) induces persistent vasoconstriction via a sustained increase in intracellular free Ca2+ concentrations ([Ca2+]i). The mechanisms of the elevation of [Ca2+]i operating at physiologically low concentrations of ET-1 are controversial. Here we report that both native ETA receptors in vascular smooth-muscle cells and recombinant ET(A) receptors expressed in mouse fibroblasts (Ltk cells) are functionally coupled with a non-selective cation channel, which is permeable to Ca2+ and is blocked by mefenamic acid. The channel is persistently activated by a low concentration of ET-1 (10(-10) M) without stimulation of inositol triphosphate (IP3) formation and mediates sustained vasoconstriction.

Animals↗

PubMed1995

[Increased production of nitric oxide in the immediate and late asthmatic responses in models of guinea pig experimental asthma].

Nitric oxide is produced in mammalian airways by constitutive and inducible nitric oxide synthase, and endogenous nitric oxide can be detected as exhaled gas. Patients with asthma have large numbers of airway epithelial cells and inflammatory cells that contain nitric oxide synthase, and nitric oxide levels in exhaled air are high during immediate asthmatic responses. To examine the dynamics of nitric oxide synthase in the tracheas of guinea pigs, cumulative dose-response studies of 5-HT were done on tracheal strips, in the presence or absence of arginine and its analogues. This assay indicated that relative the activity of nitric oxide synthase was greater 6 hr after the challenge than immediately after, which suggests that nitric oxide is involved in the pathogenesis of bronchial asthma attacks.

Animals↗

PubMed1994

Secreted form of amyloid beta/A4 protein precursor (APP) binds to two distinct APP binding sites on rat B103 neuron-like cells through two different domains, but only one site is involved in neuritotropic activity.

Recent studies have identified the Alzheimer's disease amyloid beta/A4 protein precursor (APP) as a trophic and/or tropic protein on several types of cells, including fibroblasts, primary culture neurons, PC12 cells, and B103 neuron-like cells. Many trophic proteins bind heparin, and it is believed that the heparin-binding domain is crucial for the trophic activity of these proteins. APP also binds heparin. The current studies were undertaken to examine the hypothesis that the neuritotropic activity of APP requires heparin binding. It was found that APP produced in E. coli bound B103 cells through detergent-extractable molecules. Approximately 50% of the binding sites were heparinase-sensitive, and heparin and heparan sulfate competed for APP binding to these sites. The heparinase-insensitive sites were recognized by a stretch of 17 amino acids of APP (residues 319-335) that contains the neuritotropic activity of APP. A mutant APP with a deletion at this site was capable of binding to the heparinase-sensitive sites, although this molecule was not neuritotropic to B103 neuron-like cells. Therefore, the neuritotropic site and the heparin-binding site are distinct in APP, and the neuritotropic effect of APP is produced through its binding to detergent-extractable and heparinase-insensitive sites.

Amyloid beta-Protein Precursor↗

PubMed1994

Serum levels of major basic protein in patients with or without eosinophilia: measurement by enzyme-linked immunosorbent assay.

A bone marrow proteoglycan (BMPG) has been purified which consists of the same amino acid sequence as that of pro-MBP, and produced two anti-BMPG mAbs. Serum levels of major basic protein (MBP), a cationic protein rich in the eosinophil granule, were measured in patients with eosinophilia or allergic diseases by an enzyme-linked immunosorbent assay (ELISA) using these mAbs. The serum levels of MBP in patients with eosinophilia (n = 64) and in those with allergic diseases without eosinophilia (n = 32) were elevated significantly (P < 0.001 and P = 0.038, respectively). There was a weak positive correlation between the serum levels of MBP and the eosinophil counts in the patients with eosinophilia (r = 0.38). Among these patients, extremely high serum levels of MBP were found in those with hypereosinophilic syndrome (HES) and Kimura's disease. Serum levels of MBP decreased more slowly than the eosinophil counts in patients with eosinophilia when treated by glucocorticoids. We conclude that measurement of serum levels of MBP is useful in evaluating the total-body proliferation and infiltration of eosinophils more accurately than following-up the eosinophil counts alone.

Aged↗

PubMed1994

Fine vasculature of hepatoma in Chinese hamsters (Cricetulus griceus); scanning electron microscopy of resin casts of blood vessels.

Scanning electron microscopy of resin casts was carried out on the vascular system of hepatoma in Chinese hamster. Casts of capillaries in the hepatoma were thin and fragmentary and formed a fine randomly arranged network in contrast to those in the liver with radial arrangement and central veins in centrilobular regions. Capillaries in the cancer merged into superficial venules corresponding to central veins while those in the border region merged into sinusoids of adjacent liver tissue. The superficial venules connected to tributaries of hepatic veins to drain into the posterior vena cava. Neovascularization did not occur by sprouting and anastomosing to form hair-pin loops of capillaries but by division of pre-existing vessels into smaller vessels, thus increasing the number of capillaries. The hepatic artery feeding the cancer was seemingly intact. There was no indication of arterio-portal shunts in the hepatoma.

Animals↗

PubMed1994

[Reproductive and developmental toxicity studies of lactitol (NS-4) (1)--Fertility study in rats by oral administration].

A study of fertility and fetal development was conducted in Sprague-Dawley rats. Male rats were given lactitol, a hepatic encephalopathy drug, orally from 63 days before mating to the end of mating period. Female rats were given from 14 days before mating to day 7 of pregnancy. The dose levels for both males and females were 0 (control), 0.7, 2.65 and 10 g/kg. The females were sacrificed on day 20 of pregnancy for examination of their fetuses. The decrease in food consumption in either male or female was observed in the intermediate and high dose groups. The high dose caused soft stool, diarrhea and increase in water consumption in either male or female. Moreover, the high dose caused salivation and suppression of body weight gain in male. In the pathological examination, the enlargement of cecum were observed in male of the intermediate and high dose groups. The increase in cecum weight were observed in male in all lactitol groups, and in female of the high dose group. Lactitol did not affect on copulation and fertility indexes in either male or female rats. Lactitol failed to affect on estrous cycle in female rats, and number of corpora lutea, implantations and preimplantation egg losses. In the fetal examination, lactitol did not affect on the development of live fetuses. The results show that no-effect dose levels of lactitol are less than 0.7 g/kg in male rats and 0.7 g/kg in female rats for general toxicity, and 10 g/kg for reproductive function in parent animals and fetuses.

Administration, Oral↗

PubMed1994

[Reproductive and developmental toxicity studies of lactitol (NS-4) (2)--Teratogenicity study in rats by oral administration].

A teratogenicity study of lactitol, a hepatic encephalopathy drug, was conducted in Sprague-Dawley rats. Female rats were given lactitol orally at dose levels of 0 (control), 0.7, 2.65 and 10 g/kg from day 7 to day 17 of pregnancy. Twenty-two female rats per dose level were sacrificed on day 20 of pregnancy for examination of their fetuses, and thirteen pregnant rats per dose level were allowed to deliver naturally for postnatal examination of their offspring. The high dose of lactitol caused diarrhea or soft stool in pregnant rats. The food consumption of female rats decreased in the intermediate and high dose groups. The water consumption of female rats increased in the high dose group. The drug failed to alter the body weight of female rats. The weights of cecum of dams increased in the intermediate and high dose group. The high dose caused enlargement of cecum in dams. The drug failed to alter the numbers of corpora lutea and implantations, fetal mortality, the number of live fetuses, body weight of live fetus, sex ratio, and external, visceral and skeletal development of fetuses. Lactitol did not affect the delivery of dams, the number of live newborns, birth index, external development, body weight, viability index, weaning index, and sex ratio of weanlings. Nor did lactitol have any adverse effect on the postnatal development of the first (F1) generation offspring, such as differentiation, emotionality, motor ability, learning ability or reproductive performance. Nor did lactitol have any adverse effect on the second (F2) generation offspring. The results show that no-effect dose levels of lactitol are 0.7 g/kg for general toxicity in mother animals, 10 g/kg for reproductive function in mother animals and their offspring.

Abnormalities, Drug-Induced↗

PubMed1994

[Reproductive and developmental toxicity studies of lactitol (NS-4) (4)--Perinatal and postnatal study in rats by oral administration].

A perinatal and postnatal study of lactitol, a hepatic encephalopathy drug was conducted in Sprague-Dawley rats. Female rats were given lactitol orally at dose levels of 0 (control), 0.7, 2.65 and 10 g/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats per level were allowed to deliver naturally for postnatal examination of their offspring. The high dose caused diarrhea or soft stool in dams. The high dose suppressed the body weight of dams during the perinatal period. The food consumption of dams decreased in the intermediate and high dose groups. The water consumption of dams increased in the high dose group. The high dose caused enlargement of cecum and increase of weights of cecum in dams. The drug failed to affect the delivery of dams and gestation index. However, high dose caused prolongation of gestation period. Two dams in the high dose group failed to nurse their all newborns during early lactation. The drug did not affect the number of live newborns, birth index, external appearance, body weight, viability index, weaning index, and sex ratio of weanlings. Nor did lactitol have any adverse effect on the postnatal development of the first (F1) generation offspring, such as differentiation, emotionality, motor ability, learning ability or reproductive performance. Nor did lactitol have any adverse effect on the second (F2) generation offspring. The results show that the no-effect dose levels of lactitol are 0.7 g/kg for general toxicity in mother animals, 2.65 g/kg for reproductive function in mother animals, and 10 g/kg for their offspring.

Administration, Oral↗

PubMed1994

[Clinical features and diagnosis of paroxysmal nocturnal hemoglobinuria: correlates with the deficiency of GPI-anchored membrane proteins].

Glycosyl phosphatidylinositol (GPI)-anchored membrane proteins are deficient in the blood cells affected by paroxysmal nocturnal hemoglobinuria (PNH). The relation of the deficiencies of CD59 and CD14 with the clinical features of PNH are reported. CD59 binds to complement components C8 and C9 derived from human sera and inhibits the C5b-9-mediated hemolysis in a species-selective manner. The CD59-binding sites were revealed to be localized in the alpha subunit of C8 and in the "b" domain of C9 (thrombin fragment). The deficiency of CD59 in PNH is causatively related to the hemolytic features in PNH. A monocyte differentiation antigen, CD14, is deficient in the affected PNH monocytes. CD14 is reported to be one of the receptors to lipopolysaccharide (LPS). LPS-binding to the monocytes were revealed to be mediated through CD14 on monocytes. Enhancement of LPS-binding to monocytes by the presence of serum was not seen to PNH-affected monocytes. PNH-affected monocytes showed impaired TNF-alpha production in response to LPS. The deficiency of CD14 indicates the abnormality in PNH-affected monocytes, however, its significance in the clinical features of PNH is to be clarified.

Antigens, CD↗

PubMed1994

[A study on drug resistance of newly admitted pulmonary tuberculosis patients with special reference to the resistance to SM, INH, EB and RFP].

Previously untreated 347 tuberculosis patients newly admitted to our hospital from 1980 to 1991 with positive bacilli and the full record of the drug sensitivity tests were analysed in this study. Among them, 49 cases showed primary resistance to either of major 4 anti-tuberculosis drugs (SM, INH, EB, RFP). The results obtained were as follows: 1. The number of patients with positive bacilli increased with age. The rate of primary drug resistance in patients of age group below 49 were significantly higher than that of age group over 50. 2. The rate of resistance was 8.6% to SM, 4.0% to INH, 1.4% to RFP and 0.6% to EB. These results are consistent with the results of studies of the Tuberculosis Research Committee, Ryoken. EB was frequently substituted to resistant drugs. 3. There was no significant difference between a group with primary resistance and a sensitive group in the various risk and intractable factors, laboratory data as a indicator of risk factors, and in the results of tuberculin skin test. There was also no significant difference in the rate of culture negative conversion of tubercle bacilli and the improvement in radiological findings. 4. We could rarely find the source of infection in 49 cases with primary resistance. In only 5 cases, family contacts were suspected and in another 1 case, the contact in a work place was suspected.

Adult↗

PubMed1994

[A case report of the maze procedure with mitral valve replacement].

The maze procedure was performed simultaneously with mitral valve replacement for atrial fibrillation and mitral stenosis in a 66-year-old female. On the first postoperative day, the cardiac status deteriorated suddenly due to a very rapid heartbeat which was later diagnosed as a 1:1 AV conduction of atrial flutter. The atrial flutter responded to an injection of verapamil and changed to a 2:1 conduction. Although atrial flutter had continued until the thirteenth postoperative day, the heart achieved sinus rhythm on that day. Since then it has continued without any antiarrhythmic drugs except digitalis. It was difficult to make a diagnosis of the rapid heartbeat on the 12-lead ECG because P waves could not be seen clearly on the ECG. Recording the electrical cardiac status by using the temporal atrial pacing leads, which were placed during the operation, was helpful in diagnosing the heartbeat as atrial flutter. The electrophysiological examination eight weeks after the operation revealed that the sinus node function was normal and atrial flutter or atrial fibrillation could not be induced. The patient is well and in sinus rhythm 12 months after the operation.

Aged↗

PubMed1994

Peptides containing the RERMS sequence of amyloid beta/A4 protein precursor bind cell surface and promote neurite extension.

Amyloid beta/A4 protein precursor (APP) is secreted into medium by most cultured cells and can function as an autocrine factor. To study the biological function of secreted forms of APP (sAPP) on neurons, we used a clonal CNS neuronal line, B103, which does not synthesize detectable levels of APP. B103 cells transfected with APP construct developed neurites faster than the parent B103 cells when plated in a serum-free defined medium. Neurite outgrowth of B103 cells was promoted by the conditioned medium of APP-695-over-producing cells or by the bacteria-produced sAPP-695 (named KB75). A series of peptides having sequences between Ala-319 and Met-335 of APP-695 also stimulated neurite outgrowth of B103 cells. The sequence of five amino acids, RERMS (APP 328-332), within this stretch of sequence, was the shortest active peptide, although the concentration required for the neuritotropic activity was higher than that of KB75. Binding assay using 125I-labeled APP 17-mer peptide corresponding to Ala-319 to Met-335 of APP-695 as a ligand demonstrated specific and saturable cell-surface binding sites. The predicted KD value was 20 +/- 5 nM and the Bmax value was 80 +/- 8 fmol/10(6) cells. The binding could be displaced with KB75. A 17-mer peptide with reverse sequence neither induced neurite outgrowth nor competed for the binding. A bacteria-produced sAPP fragment lacking the active 17-mer sequence (named KB75 delta) did not compete with 125I-labeled 17-mer for binding or stimulate neurite extension. A peptide of sequence RMSQ (APP 330-333), which partially overlaps the active sequence RERMS, could block the neuritotropic effects of both KB75 and the 17-mer at higher concentrations. APP 17-mer was also found to induce the accumulation of inositol polyphosphates, suggesting that the APP 17-mer effects involve activation of inositol phospholipid signal transduction systems. These data indicate that sAPP induces neurite extension through cell-surface binding and that the domain containing the RERMS sequence (APP 328-332) represents the active site responsible for this function.

Amino Acid Sequence↗

PubMed1993

Biologically active domain of the secreted form of the amyloid beta/A4 protein precursor.

The amyloid beta/A4 protein precursor (APP), a large transmembrane protein, is expressed ubiquitously in many organisms, as well as in a variety of cultured cells. Studies of the synthesis and processing of APP have revealed several intricate metabolic pathways for this protein. One of these pathways involves the cleavage of APP in the middle of the beta/A4 domain and results in the secretion of the large amino-terminal portion of the protein. The biological function of this secreted form of APP has been the subject of intense investigation by several groups and various activities have been described for the different domains of APP studied. Our initial approach was to create a fibroblast cell line in which APP expression is dramatically reduced. These fibroblasts, called A-1, have a very slow growth rate. Addition of exogenous APP in the medium of A-1 cells restores their growth to the level of normal parent fibroblasts, demonstrating a growth factor-like activity for the secreted form of APP. Using APP fragments made in bacteria as well as synthetic peptides, we have been able to locate the active site of APP within a domain of 17 amino-acids (Ala319-Met335). This domain of APP can stimulate neurite extension of cultured neuroblastoma cells and it is proposed that APP mediates this effect through binding to a cell surface receptor, triggering intracellular transduction mechanisms. Thus, the secreted form of APP can function as a growth and/or differentiation factor and the site involved in these activities is within a 17-mer domain in the middle of the molecule. Our current lines of research seek to further characterize the mechanisms of APP function as well as its activity in vivo.

Amino Acid Sequence↗

PubMed1993

Amino acid sequence RERMS represents the active domain of amyloid beta/A4 protein precursor that promotes fibroblast growth.

The growth of A-1 fibroblasts depends on exogenous amyloid beta/A4 protein precursor (APP), providing a simple bioassay to study the function of APP. Our preliminary study, testing the activity of a series of fragments derived from the secreted form of APP-695 (sAPP-695) on this bioassay, has shown that at least one of the active sites of sAPP-695 was localized within a 40-mer sequence (APP296-335, Kang sequence; Roch, J.-M., I. P. Shapiro, M. P. Sundsmo, D. A. C. Otero, L. M. Refolo, N. K. Robakis, and T. Saitoh. 1992. J. Biol. Chem. 267:2214-2221). In the present study, to further characterize the growth-promoting activity of sAPP-695 on fibroblasts, we applied a battery of synthetic peptides on this bioassay and found that: (a) the sequence of five amino acids, RERMS (APP328-332), was uniquely required for the growth-promoting activity of sAPP-695; (b) the activity was sequence-specific because the reverse-sequence peptide of the active domain had no activity; and (c) the four-amino-acid peptide RMSQ (APP330-333), which partially overlaps the COOH-terminal side of the active sequence RERMS, could antagonize the activity of sAPP-695. Furthermore, a recombinant protein which lacks this active domain (APP20-591 without 306-335) did not promote fibroblast cell growth, suggesting that this domain is the only site of sAPP-695 involved in the growth stimulation. The availability of these biologically active, short peptides and their antagonists should prove to be an essential step for the elucidation of APP involvement in regulation of cellular homeostasis.

Amino Acid Sequence↗

PubMed1993

Induction of Fc gamma R-III (CD16) expression on neutrophils affected by paroxysmal nocturnal haemoglobinuria by administration of granulocyte colony-stimulating factor.

The inducibility of glycosyl-phosphatidylinositol (GPI)-anchored proteins on affected paroxysmal nocturnal haemoglobinuria (PNH) neutrophils (PMN) after both in vitro and in vivo stimulation was investigated. Fc gamma R-III (CD16), decay-accelerating factor (DAF/CD55) and 20 kD homologous restriction factor (HRF20/CD59) were demonstrated to be concurrently deficient on unstimulated defective PNH PMN. Upon in vitro stimulation with either N-formyl-methionyl-leucyl-phenylalanine (fMLP), zymosan-activated serum (ZAS), or recombinant human granulocyte colony-stimulation factor (G-CSF), neither CD16 nor CD55 expression was induced on defective PNH PMN. G-CSF was administered to two patients with PNH when their conditions were complicated by bacterial infections, or to prevent infections associated with the extraction of teeth or cataract surgery. CD16 expression was induced on the defective PNH PMN in both cases during the administration of G-CSF, but the expression of CD55 and CD59 was not. CD16, induced on the defective PNH PMN during the administration of G-CSF, was phosphatidylinositol-specific phospholipase C (PIPLC)-sensitive, implying that it had GPI-linkage to the membranes. The patients treated with G-CSF recovered from infection or evaded infection. These observations suggest that a deficiency of GPI-anchored proteins is not always seen in defective PNH blood cells, at least under certain stimulation conditions.

Antigens, CD↗