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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 73 records · Page 4Linked to original sources
PubMed1995

Prediction of prognosis of primary biliary cirrhosis in Japan.

The clinical profile of primary biliary cirrhosis in Japan was clarified on the basis of data on 1066 patients attending 212 hospitals and institutions in this country. Six hundred and twelve patients (57.4%) were asymptomatic. The majority of the patients were middle-aged women. Pruritus was the most frequent initial symptom of symptomatic primary biliary cirrhosis. Antimitochondrial antibodies were positive in 877 patients (82.5%). Sjögren's syndrome was the most common associated autoimmune disease. Liver biopsy was performed in 753 patients at the time of diagnosis, and histological staging by Scheuer's classification indicated that 307 (43.7%) patients were in stage I and 222 (31.6%) were in stage II. The most frequent causes of death were hepatic failure and/or gastrointestinal bleeding, which affected 166 (78.3%) of the 212 patients who died. Statistical analysis using Cox's regression method revealed that the patient's age and the serum bilirubin, albumin, and total cholesterol concentrations were significant predictors of the prognosis. A prognostic index was also calculated that could be used to predict the duration of survival for patients with primary biliary cirrhosis.

Adult↗
PubMed1995

Mutations in rpoB gene of rifampicin resistant clinical isolates of Mycobacterium tuberculosis in Japan.

In Mycobacterium tuberculosis, involvement of alterations of the RNA polymerase beta subunit in resistance to rifampicin has been described by Telenti et al. To determine if the same correlation could be observed between the mutation of the rpoB gene and clinically isolated M. tuberculosis of the rifampicin-resistant phenotype in Japan, 47 strains of M. tuberculosis of the rifampicin-resistant phenotype, 17 of the rifampicin-susceptible phenotype, and 4 type strains were examined. A 411-base pair (bp) rpoB fragment was amplified by the polymerase chain reaction and subjected to solid phase direct sequencing. By comparing the nucleotides, mutation involving 8 conserved amino acids were identified in 44 of the 47 (93.6%) rifampicin-resistant isolates, but in none of the 17 sensitive isolates and 4 type strains. All mutations found were clustered within a region of 23 amino acids. Thus, similar to the results reported by Telenti et al., substitution of a limited number of highly conserved amino acids encoded by the rpoB gene appears to be the molecular mechanism responsible for resistance to rifampicin in Japanese clinical isolates of M. tuberculosis. Our results suggest that direct DNA sequencing of the rpoB gene may be a reliable method for identifying rifampicin-resistant M. tuberculosis strains among Japanese clinical isolates.

Amino Acid Sequence↗
PubMed1995

Nonselective cation channels coupled with tachykinin receptors in rat sensory neurons.

1. Effects of substance P (SP) and other tachykinins on membrane currents were investigated using whole cell voltage clamp in cultured sensory neurons isolated from rat dorsal root ganglia. 2. SP (100 nM) evoked an inward current in two-thirds of the cells at negative potentials. In most of the cells that generated the inward current in response to SP, capsaicin also activated an inward current. The SP-evoked inward current was not observed in cells loaded with 2 mM guanosine 5'-O-(2-thiodiphosphate) (GDP beta S). 3. Neurokinin A (NKA) or neurokinin B (NKB) also activated an inward current. At 100 nM of each agonist, the order was NKB > NKA > SP with respect to activated current amplitude. 4. The tachykinin-activated current was reversed around +10 mV with a standard extracellular solution containing 140 mM NaCl. The reversal potential became more negative when extracellular NaCl was reduced by substituting with sucrose. The inward current was also activated in cells bathed in an extracellular solution containing Cs+, tetraethylammonium (TEA) or N-methyl-D-glucamine (NMDG) as a major cation instead of Na+. The order of permeability, determined from the reversal potential of the current, was Cs+ not equal to Na+ > TEA > NMDG. The amplitude of the inward current activated by NKB was increased when extracellular Na+ was replaced with Cs+, TEA or NMDG. 5. Permeability of Ca2+ was tested using an extracellular solution containing Ca2+ as the only cation (111.8 mM Ca2+ outside). Under this condition, NKB evoked an inward current that reversed around +30 mV. 6. The results suggest that SP and other tachykinins activate nonselective cation channels, which are also permeable to Ca2+, through receptors which are more responsive to NKB than to SP or NKA. The channel activation may serve as a mechanism underlying tachykinin-mediated excitatory neurotransmission in sensory neurons.

Animals↗
PubMed1995

Role of endogenous endothelin in gastric mucosal injury induced by hemorrhagic shock in rats.

We examined the role of endogenous endothelin in the pathogenesis of hemorrhagic shock-induced gastric mucosal injury in rats. Animals were bled to induce hypotension (20-30 mm Hg) for 20 min and the shed blood was retransfused. Rats were sacrificed at the end of hypotension, 20 min, and 60 min after retransfusion, respectively. Gastric erosions were induced with this experimental protocol. The total area of erosions was minimal only at the end of hypotension, and increased time-dependently after blood retransfusion. Plasma endothelin concentration significantly increased at the end of hypotension and persistently increased after retransfusion, whereas in gastric endothelin concentration a significant increase was observed at 60 min after retransfusion. The gastric mucosal hemodynamics as assessed by continuous measurement with reflectance spectrophotometry showed ischemia associated with congestion after retransfusion. Treatment with a monoclonal antibody against endothelin (0.2 mg/100 g BW/h) prevented these hemodynamic disturbances, rendering a significant decrease in the total area of erosions at 20 and 60 min after retransfusion. These results strongly suggest an important role of circulating endothelin in the pathogenesis of hemorrhagic shock-induced gastric mucosal injury through mucosal microcirculatory perturbation.

Animals↗
PubMed1995

Effect of oral multiple-dose administration of anti-inflammatory flurbiprofen chimera drug on gastric lesion, other toxicities and disposition kinetics.

Flurbiprofen (FP) was esterified with a histamine H2-antagonist, PPA (N-[3-(3-(1-piperidinylmethyl)phenoxy)-propyl]-2-(2- hydroxyethylthio)acetamide), to yield a chimera drug, FP-PPA, and its protective effect toward gastric lesions, other toxicities and the disposition kinetics were investigated, as compared to those of FP, in multiple oral administration to rats for 2 weeks. FP-PPA scarcely formed any disorder of the gastric mucosa following multiple oral administration. The body weight changes and hematological and serum biochemical parameters were found to be similar to those in the control group. Some drug metabolizing enzyme activities tested were the same as those of the control group. Further, the pharmacokinetic parameters were found to be the same after both single and multiple oral administration. On the other hand, in the FP treated group, the inhibition of body weight increase and changes in serum biochemical and hematological parameters were observed due to malabsorption. The absorption rate constant was increased significantly after multiple administration as compared to that of single administration. It is suggested that these changes in the absorption process of FP are due to variations in gastrointestinal permeability derived from gastrointestinal damage. The results obtained here indicate clearly that the chimera drug FP-PPA scarcely forms any disorder of the gastric mucosa, even after multiple oral administration, and is thus a potential candidate for oral use.

Absorption↗
PubMed1995

Organization of the sources of reticulospinal projections in the chicken by means of a confocal laser scanning microscope.

To investigate the manner of reticulospinal projections in chickens, two different fluorescent dyes (Fast-Blue and Diamidino-Yellow) were injected into the lumbar and sacral segments. Results showed that the main projections to the spinal segments are clearly different for the pons and medulla. The main source of the medulospinal projections was in the ventral reticular formation, and the projections from the dorsal reticular formation were sporadic. On the other hand, the main pontine projections arose from the dorsolateral tegmentum and they projected to the sacral segments. In contrast, projections to the lumbar segments were somewhat more dominant in the ventromedial tegmentum than in the dorsolateral tegmentum. Double projection neurons were observed in the ventrolateral reticular formation and dorsolateral tegmentum where there were many cells of origin of the spinal descending projections. The reticulospinal projections manner of birds was organized dorsoventrally, and it was comparable with that of mammals.

Amidines↗
PubMed1995

Sex differences in the shapes of several parts of the young Japanese face.

For the purpose of studying the sex differences of the human face we collected five separate images, which consist of several parts of the face, from frontal view photographs of 48 male and 52 female college students. We traced outlines of their faces with simple lines (traced items), and made reproductions of the photographs of their eyes, mouth and nose by using a copying machine (reproduced items). The test subjects were 16 males and 8 females. They looked at parts of the face shown in each image, and categorized them individually by judging on their sex. Then, we calculated the percentages of correct judgments (percentage correct) for each image. By comparing the percentage correct between male and female we concluded that the sex of the subjects did not affect the results of their judgments. In the traced items the percentage correct for the face as a whole, which contained the outlines of the eyes, mouth, nose and the lower jaw, was 69%, but it decreased to 61% when the outline of the lower jaw was removed. Hence, the outline of the lower jaw apparently has a characteristic shape easily noticed by males. In the reproduced items the percentage correct was 65% for the eyes, 68% for the mouth and 58% for the nose. The mouth, therefore, has more distinguishing characteristics than the eyes or nose, especially with females. On the other hand, there is no correlation between the percentage correct for the eye, mouth and nose items. Hence, we concluded that the sexual specificity for the shape of the young Japanese face appears on their parts independently.

Adult↗
PubMed1995

Exhibition of anti-platelet effect of isocarbacyclin methyl ester and its free acid via an increase in cAMP in platelets.

Isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) and its free acid (CAS 88911-35-7, TEI-7165) are chemically stable analogues of prostaglandin (PG) I2. The cAMP increasing activities of TEI-9090 and TEI-7165 were investigated. TEI-9090, TEI-7165, PGI2, and PGE1 caused the accumulation of cAMP in rabbit and human platelets. The effects of TEI-9090, TEI-7165, and PGE1 were longer lasting than the effect of PGI2. Each drug concentration-dependently increased the cAMP level in rabbit and human platelets. The order of cAMP-increasing activity was PGI2 > PGE1 = TEI-9090 = TEI-7165 in rabbit platelets and PGI2 > TEI-9090 = TEI-7165 > PGE1 in human platelets. The antiplatelet aggregation activity of TEI-9090 in rabbit and human platelets was remarkably decreased by the addition of an esterase inhibitor, diisopropyl fluorophosphate (DFP). However, this activity of TEI-7165 was not affected by the inhibitor. In the presence of DFP, the cAMP accumulation by TEI-9090 in rabbit platelets was almost completely inhibited but that by TEI-7165 was not inhibited. These results suggest that TEI-9090 is deesterified to TEI-7165 and that this free acid then inhibits platelet aggregation via an increase in the cAMP level in the platelets.

Alprostadil↗
PubMed1995

Anti-platelet effects of isocarbacyclin methyl ester on human and rabbit platelets in vitro.

Anti-platelet effects of isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) and of its free acid form, TEI-7165 (CAS 88911-35-7) were compared with those of prostaglandin (PG) I2 and PGE1. TEI-9090 and TEI-7165 dose-dependently inhibited human and rabbit platelet aggregation and human platelet adhesion in vitro. The IC50 values of TEI-9090, TEI-7165, PGI2, and PGE1 against ADP-induced human (rabbit) platelet aggregation were 22.90 (25.00) ng/ml, 2.78 (6.46) ng/ml, 1.67 (3.34) ng/ml, and 19.91 (8.32) ng/ml, respectively; and those against human platelet adhesion were 3.47 ng/ml, 0.13 ng/ml, 0.25 ng/ml, and 1.45 ng/ml, respectively. TTC-909, a product incorporating TEI-9090 in lipid microspheres, had an aggregation inhibitory effect similar to that of TEI-9090 in human platelets. The aggregation inhibitory effect of TEI-9090 and TTC-909 increased with incubation time, and reached a level similar to that of TEI-7165. In contrast, the aggregation inhibitory effect of TEI-7165 remained constant for 120 min, whereas that of PGI2 decreased with time. TEI-9090 and TEI-7165 also enhanced the disaggregation of human platelets at nearly the same concentration as they exerted their inhibitory effect on aggregation. The order of anti-platelet activities, compared at each optimum incubation point, were PGI2 approximately equal to TEI-7165 approximately equal to TEI-9090 (approximately equal to TTC-909) > PGE1 in human and rabbit platelets. These results indicate that TEI-9090 (TTC-909) and its active metabolite, TEI-7165, may be a potent anti-platelet drug.

Animals↗
PubMed1995

Ex vivo anti-platelet effects of isocarbacyclin methyl ester incorporated in lipid microspheres in rabbits.

Effect of TTC-909, a chemically stable isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) incorporated in lipid microspheres, on platelet aggregation was tested in conscious rabbits. TTC-909 significantly inhibited platelet aggregation induced by ADP at early times after bolus i.v. injection from the dose of 0.3 micrograms/kg in a dose-dependent manner. Similarly, TTC-909 significantly inhibited platelet aggregation induced by ADP during the venous infusion from the dose of 100 ng/kg/min, also in a dose-dependent manner. The anti-platelet effect of TTC-909 was observed at a dose lower than that inducing hypotensive effect when given as both bolus i.v. and venous infusion. On the other hand, prostaglandin (PG) E1 (LM)--PGE1 incorporated in lipid microspheres--reduced blood pressure without having an anti-platelet effect. These results indicate that TTC-909 may be a potent anti-thrombotic drug.

Alprostadil↗
PubMed1995

The effects of bifemelane hydrochloride on depressive illness of the elderly.

The therapeutic efficacy, utility and safety of bifemelane hydrochloride were studied in 52 elderly depressive patients. The drug was administered as a tablet containing 50 mg orally three times daily for 8 consecutive weeks. The final global improvement rating and global utility rating were respectively 80.8 and 73.1 percent for all patients. The improvement rates on the Hamilton depression rating scale (HAM-D) were more than 60% for depressed mood, guilt, suicide, middle insomnia, delayed insomnia, psychotic anxiety, gastro-intestinal symptom, hypochondriasis, depersonalization and derealization. The rates regarding global symptoms evaluated by the Psychoneurotic rating scale for doctor's use were more than 60% for tension, agitation, irritability and excitement, phobia, depression, hypochondria and nocturnal delirium in psychotic symptoms, and insomnia in addition to palpitation in somatic symptoms. A significant decrease was also observed in the symptoms covered by the Self-rating depression scale of Zung after treatment with this drug. There were no instances of side-effects, nor any abnormalities in laboratory tests, encountered throughout the trial. Therefore, bifemelane hydrochloride is of value for the treatment of geriatric depression.

Aged↗
PubMed1995

[ATP as a neurotransmitter in the brain: its possibility based upon recent findings].

We discuss here possible neurotransmitter roles of extracellular ATP in the central nervous system. Important findings concerning the effects of ATP on central neurons have been made in the last few years. A fast neurotransmitter role of ATP in rat medial habenula reported by Edwards et al (1992) may be the best example. In rat cultured hippocampal neurons, we have found that ATP evokes postsynaptic currents, and increases the intracellular Ca2+ concentration. In addition, ATP also produces a "long-term potentiation like effect" in these cells. Receptors for ATP are generally divided into two classes: one class is coupled with ion channels and the other class is coupled with GTP-binding proteins. In cultured hippocampal neurons, the GTP-binding protein-coupled receptors are present and promote the inhibition of K+ channels. Although the channel-coupled receptors have not been identified in the hippocampal neurons, these channels have been found in nucleus solitarii and locus coeruleus. Several types of ATP receptors have been cloned very recently. These cloned receptors, combined with molecular biological techniques, will allow great progress in this field.

Adenosine Triphosphate↗
PubMed1995

Expression of estrogen receptor related protein (p29) and estradiol binding in human arthritic synovium.

OBJECTIVE: We investigated the expression of estrogen receptors (ER) and the presence of estradiol in human synovial tissues from subjects without arthritis and patients with traumatic arthritis, osteoarthritis, and rheumatoid arthritis. METHODS: Synovial tissues were immunostained using ER-D5 monoclonal antibody (Mab) directed toward an ER related protein (p29), ER-ICA Mab directed toward nuclear ER, and antiestradiol serum. Fluorescent estradiol was used to demonstrate specific estradiol binding to ER. RESULTS: (1) p29 was present predominantly in hyperplastic synovial lining cells and smooth muscles of blood vessels. (2) Exogenous estradiol bound to synoviocytes and sublining macrophage-like cells in the inflamed synovium. (3) Endogenous estradiol was also detected in hyperplastic lining cells and macrophage-like cells in arthritic synovium. CONCLUSION: Our study demonstrated the expression of ER in arthritic synovium and suggested that estrogen modulates local inflammation in various joint diseases via synoviocytes as well as sublining macrophage-like cells.

Adolescent↗
PubMed1995

Annual screening for oral cancer and precancer by invitation to 60-year-old residents of a city in Japan.

Since 1986, annual screening for oral cancer and precancer by postal invitation has been undertaken among 60-year-old residents of Tokoname city, Japan. Clinical examination of the oral soft tissues is performed by groups of four different, specially trained general dental practitioners in the city health centre on one day each year. Following screening each subject receives an individual consultation with an oral medicine specialist. Individuals considered to need full diagnostic follow up or treatment are advised to attend a secondary care referral facility. Between 1986 and 1993, 802 out of 5187 eligible residents (15.5 per cent) were screened of whom 38 (4.7 per cent) were designated by the screeners as positive for oral cancer, erythroplakia, leukoplakia, lichen planus or chronic candidosis. Of these, 32 were referred and 25 attended for follow up examination in hospital departments by specialists with full diagnostic back up facilities. Twenty subjects were confirmed as having a potentially malignant lesion. For these referred patients only, the proportion of correct decisions by the screeners out of all oral cancer/precancer screening decisions was 81 per cent. Positive and negative predictive values for those attending for follow up were 0.80 and 0.82 respectively. Ways of improving the effectiveness and adequacy of the programme are considered.

Biopsy↗
PubMed1995

[Simultaneous operations for both the repair of the aortic arch aneurysm and repeated CABG].

A 73-year-old female complaining of left thoracic pain was referred to our hospital. In 1988, she had the first CABG of the left circumflex coronary artery (CX) and right coronary artery. On admission in April 1994, chest X-ray and CT scan revealed a saccular aortic aneurysm, 5 x 5 cm in size, extending to the distal to the left subclavian artery. Coronary arteriography showed a patency of the CX graft, but 99% stenosis of the proximal left anterior descending branch (LAD) with delayed opacification. After the repeated median sternotomy, cardiac arrest was achieved with the aortic cross clamping and St. Thomas Hospital solution infusion. CABG to the LAD branch using a saphenous vein was accomplished. Following this, the replacement of the aortic aneurysmal lesion with a prosthetic graft was performed under the selective cerebral perfusion with deep hypothermia. Proximal anastomosis of the vein graft was completed during a rewarming period. The operation was performed without complications. Postoperative course was satisfactory except a few minor transient complications such as athelectasis of the left upper lobe and the intra-thoracic hematoma. After one month's hospitalization, she was discharged, and currently (six months postoperative) remains asymptomatic.

Aged↗