Search PubMed⌕ Search

Biomedical subjects

T Imai

Publications and source records attributed to T Imai.

At least 793 records · Page 44Linked to original sources

Purification and characterization of a pyridine nucleotide glycohydrolase from rabbit spleen.

A particulate NMN glycohydrolase of rabbit spleen was solubilized with Triton X100 and purified approximately 100-fold. The enzyme was shown to have a pH maximum of 6.5, a Km of 0.25 mM, a Vmax of 5.3 mumol/min/mg protein, an activation energy of 7.9 kcal/mol, and a molecular weight of approximately 400,000. Both of the purified and the particulate enzymes exhibited identical catalytic properties with respect to substrate specificity, activation energy, pH profile and exchange reaction with nicotinic acid, except that the purified enzyme was highly activated with Triton X100 as compared with the particulate enzyme; it appears that the purified enzyme possesses the same catalytic properties as the enzyme present in the tissue and that solubilization does not significantly alter the native protein. In addition to catalytic activity with NMN, the rabbit spleen enzyme catalyzed an irreversible hydrolysis with NAD and NADP, exhibiting catalyzing activity ratios of NMN:NAD:NADP = 1.00:1.45:0.44 and Vmax/Km ratios of 1.00:1.7:2.3, respectively. These ratios of activity remained constant throughout purification of the enzyme and no separation of these activities was detected. Mutually competitive inhibition of the enzyme with Ki values similar to Km, and identical rates of thermal denaturation of the enzyme and activity-pH profiles with NMN or NAD indicated the hydrolysis of the C-N glycosidic linkage of the pyridine nucleotides to be catalyzed by the same enzyme. The enzyme was less specific for the purine structure of the substrate dinucleotides but was stereospecific for the glycosidic linkage cleaved. Nicotinamide riboside, the nicotinic acid analogs and the reduced forms were not hydrolyzed. A linear noncompetitive inhibition of NMN hydrolysis with nicotinamide indicated an ordered Uni-Bi mechanism in which nicotinamide was the first product released from the enzyme. A property that the rabbit spleen enzyme appears to share with other NAD glycohydrolases is the transglycosidation reaction. The ratio of transglycosidation reaction vs. hydrolysis catalyzed by the enzyme in the presence of NMN and nicotinic acid indicated that the enzyme could function as a primary transglycosidase rather than a hydrolytic enzyme in vivo.

Animals↗

Kinetic analysis of the transglycosidation reaction catalyzed by rabbit spleen pyridine nucleotide glycohydrolase.

Properties of the transglycosidation reaction catalyzed by rabbit spleen pyridine nucleotide glycohydrolase were characterized using a modified cyanide addition method by which initial velocities of the transglycosidation (vT) and hydrolysis (vH) of pyridine nucleotides could be monitored simultaneously. (1) The vT was routinely determined with NMN and nicotinic acid used as substrates and was observed to be maximal at pH 6. Arrhenius plots of vT and vH indicated that the activation energies for transglycosidation and hydrolysis were 8.7 and 10.7 kcal/mol, respectively. (2) The enzyme showed a broad spectrum of substrate specificity with respect to both pyridine nucleotides and bases. Of the compounds tested, NMN and nicotinic acid were shown to be the best substrates when compared on the basis of Vmax/Km values. Kinetic constants for the enzyme-catalyzed transglycosidation reaction were as follows; Km(NMN) = 0.53 mM, Km(nicotinic acid), as acid form = 15 mM, apparent Vmax = 7.8 mumol/min/mg protein, in the presence of 0.2 M nicotinic acid. (3) The ratio of vT/vH was shown to be dependent on both pH and nicotinic acid concentration. However, transglycosidation versus hydrolysis partition at a fixed pH was constant regardless of the nicotinic acid concentration employed and approximated to be 1.2 x 10(4) at the maximal pH. (4) Nicotinamide, one of the most potent inhibitors for the enzyme-catalyzed hydrolysis, was shown to function as an antagonist for the transglycosidation reaction with NMN and nicotinic acid used as substrates. The inhibition mechanism with nicotinamide was purely noncompetitive with respect to nicotinic acid; on the other hand, the double reciprocal plot of the transglycosidation velocity against NMN concentration at a fixed concentration of nicotinamide was concave downwards. (5) The equilibrium constant of the reaction, NMN + 3-acetylpyridine----3-acetylpyridine mononucleotide + nicotinamide, was 0.61, whereas the conversion of NMN with nicotinic acid to nicotinic acid mononucleotide was essentially irreversible. These enzymatic properties of rabbit spleen pyridine nucleotide glycohydrolase suggested that the enzyme should not function as a glycohydrolase but as a transglycosidase and could serve in an important mechanism for an alternative biosynthetic pathway of nicotinic acid mononucleotide, one of the precursors for NAD synthesis, when nicotinic acid is supplied.

Animals↗

Relationship between length of longitudinal extension and maximal depth of transmural invasion in roentgenographically occult squamous cell carcinoma of the bronchus (nonpolypoid type).

This study was designed to verify our hypothesis that there are two different growth types in roentgenographically occult squamous cell carcinoma of the bronchus. Serial blocks prepared from the entire bronchial tree of 83 resected specimens of occult carcinoma were used for the evaluation of the relationship between the length of longitudinal extension and the maximal depth of transmural invasion. We prepared a length-depth diagram of 92 lesions, including multifocal carcinomas, which confirmed that there are at least two types: Most of these lesions are of the creeping type, which shows a marked superficial growth; the minority are of the penetrating type, which shows a marked downward growth. The diagram suggests that occult carcinoma has a propensity either for longitudinal growth along the bronchial lumen or for transmural growth into the bronchial wall at the time of occurrence. It is likely that the penetrating type grows rapidly and becomes advanced in a short time. Identification of longer lesions of the creeping type is occasionally problematical both at bronchoscopy and at surgical treatment. The stump is usually positive for carcinoma unless frozen sections or imprint specimens of the margin of resection are examined, because it is frequently difficult to identify the proximal end of extension by bronchoscopy.

Bronchi↗

Primary malignant melanoma of the penis--a case report and a review of the literature.

A 50-year-old man had a primary malignant melanoma of the penis associated with granuloma telangiectaticum in the pigmented lesion. The patient had an operation for phimosis at the age of 20 and after the operation, he noticed a pigmented lesion at the operation site. We examined the literature and found 16 cases of primary malignant melanoma of the penis in Japan.

Biopsy↗

A physiological marker for assessing anxiety level in humans: frontal midline theta activity.

The distinct theta rhythm in the frontal midline area during performance of mental tasks has been designated as Fm theta. Sixteen male university students who failed to show any appearance of Fm theta in 3 consecutive days were given diazepam 5 mg, amobarbital 80 mg, methylphenidate 15 mg and placebo, in a double-blind, crossover design. Scores were made on the state anxiety scale of STAI; EEGs were recorded before and during performance of an arithmetic addition. The test was repeated twice: before and one hr after drug administration. Fm theta appeared following the drug administration even in those who had never shown the appearance of Fm theta, and the appearance time of Fm theta increased in the following order: diazepam greater than amobarbital greater than placebo greater than methylphenidate. The scores of STAI decreased in the same order. The speed of performed tasks was increased by methylphenidate and placebo, but decreased by amobarbital and diazepam. These results suggest that relief from anxiety might be reflected in the appearance of Fm theta and that Fm theta might be a useful tool to measure the anxiety level in humans.

Adult↗

[A case of measles in adolescents with myocarditis and pneumonia].

A 18-year-old man was admitted with fever, dry cough, erythema, conjunctivitis, and dyspnea. The case was diagnosed as measles because of the typical clinical course and the increase of measles viral antibody titre. Electrocardiogram showed transient ST-T abnormalities and the laboratory data showed transient increase of CPK. Therefore myocarditis was considered. However chest roentgenogram showed no abnormal findings. Arterial oxygen was low. The Ga scintigram revealed diffused uptake in both lungs. Microscopic examination of the transbronchial lung biopsy revealed alveolitis. In view of he above, measles pneumonia was diagnosed in this case.

Adolescent↗

Retrograde pyramidal tract degeneration in a patient with cervical haematomyelia.

Retrograde pyramidal tract degeneration has been described only very rarely in the human central nervous system. In most of these cases the thoracic or cervical corticospinal tracts were shown to have degenerated following long-standing, lower spinal cord lesions. In a 67 year old man, who lived 2 years following the rupture of a mid-cervical cavernous angioma, we observed such degeneration which reached as high as the pons. This axonal dissolution was much less manifest above the ponto-medullary junction. Large pyramidal cells of Betz were not identified in the precentral gyrus, suggesting that the parental soma of the damaged axons had undergone atrophic changes. Furthermore, the involvement of the so-called aberrant pyramidal tract in the pontine medial lemniscus indicated that retrograde degeneration had occurred there as well.

Aged↗

Further studies on the pharmacological effect of the anti-inflammatory compound, bis[2-(E-2-octenoylamino)ethyl] disulfide.

Further studies on the pharmacological effect of orally administered bis[2-(E-2-octenoyl-amino)ethyl] disulfide (compd. I-3) was examined by using several experimental models in vivo. Compound I-3 showed analgesic activity, inhibiting both acetic acid- and acetylcholine-induced writhings in mice. This compound also showed antipyretic activity against yeast-induced fever in rats, and significantly inhibited arachidonic acid-induced mortality in mice. However, it had no effect on serotonin-induced paw edema formation or platelet activating factor-acether-induced mortality in mice. The effects of compd. I-3 are suggested to be due to inhibition of prostaglandin biosynthesis.

Amides↗

Enhancement of the dissolution rates of poorly water-soluble drugs by water-soluble gelatin.

The dissolution behavior of several acidic and basic drugs from kneaded mixtures with water-soluble gelatin have been studied in comparison with that of the drug alone. The results revealed a significant increase of dissolution rate of drugs from kneaded mixtures. The water-soluble gelatin showed little interaction with any of the drugs in solution or in the solid state. Interestingly, the contact angle of the kneaded mixture was remarkably decreased compared with that of the drug powder and was found to be almost the same as that of water-soluble gelatin powder. Thus, the enhanced dissolution rate of the drug caused by water-soluble gelatin was explained by the improvement of wettability of the drug by water.

Chemistry, Pharmaceutical↗

[Dissolution and absorption behavior of meclizine dihydrochloride from soft gelatin capsules].

Two kinds of soft gelatin capsules containing meclizine dihydrochloride (MZ) were prepared by using a medium-chain length triglyceride as a base. One is a self-emulsifying type, and the other is an oil dispersing type. The release of MZ from soft capsules and its in vivo absorption behavior were examined and compared with those of a commercial tablet. The release of MZ from the self-emulsifying soft capsule which was only slightly affected by pH was greater than those from the oil dispersing soft capsule and commercial tablet. The serum levels of MZ after the administration of preparations orally to beagle dogs increased in the order of self-emulsifying soft capsule, commercial tablet, oil dispersing soft capsule. This result suggests that the self-emulsifying soft capsule is useful for the increase of the bioavailability of the drug.

Administration, Oral↗

Silent myocardial ischemia in the aged: a retrospective study from the evaluation of necropsy hearts.

The diagnosis of silent myocardial ischemia in the aged remains controversial. In this study to evaluate the basic state of silent ischemia in the aged, a total of 972 consecutive autopsy cases (mean 79.0 yrs of age) were analyzed in terms of coronary atherosclerotic diseases. The following results were obtained: (1) Severe coronary occlusive lesions simultaneously detected in the three major coronary arterial branches were found in 85 cases (8.7%), of which 10 (12%) had neither history of angina nor myocardial infarction (MI), which may correspond to one representation of silent ischemia. (2) There were 218 cases of MI (22.4%), of which 106 (49%) were never documented to have MI during life. The latter may correspond to unrecognized MI. It was considered to be caused by 1) small or middle-sized MI in 66 cases and 2) lateral or nontransmural MI in 29 out of 40 large MI cases (more than 4.9 cm in diameter). (3) 30 cases (54%) out of 56 fresh and large MI with a correct diagnosis revealed no chest pain. This is an incidence of painless MI in the aged. This painless group showed a significant difference in the incidence of a correct diagnosis of MI (51% vs 89%), combined arrhythmia (47% vs 79%) and the association of CVD (47% vs 11%) compared with chest pain group.

Aged↗

Exacerbation of hypercapnia and acidosis of central venous blood and tissue following administration of sodium bicarbonate during cardiopulmonary resuscitation.

Administration of sodium bicarbonate during cardiopulmonary resuscitation (CPR) is controversial, and our aim was to elucidate whether or not its administration is beneficial by analyzing the acid-base status and the level of carbon dioxide in central venous blood during CPR, and their changes following administration of sodium bicarbonate. Six patients were studied. They had all been admitted to the intensive care unit (ICU), had already had pulmonary arterial or central venous catheters inserted, and had acute episodes of circulatory collapse during their stay in the ICU. The following phenomena were observed: 1) hypercapnia and acidosis of central venous blood were prominent during both cardiogenic shock and CPR, although arterial hypocapnia was maintained by hyperventilation; 2) administration of sodium bicarbonate during cardiogenic shock and CPR induced exacerbation of hypercapnia and acidosis of central venous blood; 3) when arterial hypercapnia was present due to disturbed ventilation, administration of sodium bicarbonate exacerbated hypercapnia and acidosis of both arterial and central venous blood; 4) administration of sodium bicarbonate did not induce hypercapnia of central venous blood in a septic shock patient in whom the septic hyperdynamic state was prevalent in spite of low systemic perfusion pressure. It was concluded that hypercapnia and acidosis of the central venous blood and tissues were exacerbated by administration of sodium bicarbonate during CPR, and that such an effect might be dependent on the severity of the decrease in tissue perfusion.

Acid-Base Equilibrium↗

Stenotic lesions and length of the left main coronary artery in the aged.

To evaluate lesions of the left main coronary artery (LM) in the aged, a pathologic study was performed on a total of 972 consecutive autopsy cases over 60 years of age. The study population consisted of 503 men and 469 women with an average age at death of 79.0 years. In this study the degree of narrowing and length of the LM were evaluated in all cases (T), and the 141 cases with normal hearts (N) were compared with the 202 cases with myocardial infarction (MI). The following results were obtained: (1) the average coronary stenotic index (CSI) was 9.1/15 in T, 5.8/15 in N and 11.2/15 in MI (N less than MI, p less than 0.001), (2) the grade of narrowing in the LM (LMG), when 100% obstruction of the LM is counted as 5, was 1.8 +/- 0.9 in T, 1.3 +/- 0.6 in N and 2.3 +/- 1.1 in MI (N less than MI, p less than 0.001). Cases showing more than 75% narrowing of the LM were found in 58 (6%), of which 35 cases belonged to MI, but development of MI directly due to lesions in the LM was found in only 9 patients (4.5% among MI), (3) the average length of the LM (LML) was 9.4 +/- 4.4 mm in T, 9.0 +/- 4.2 mm in N and 9.3 +/- 3.8 mm in MI (N vs MI; n.s.). Cases presenting left coronary artery dominance (n = 82) or a balanced type (n = 159) showed shorter LML than those with right coronary artery dominance (n = 729) (8.5 +/- 4.0 mm, 8.8 +/- 4.6 mm and 9.7 +/- 4.4 mm, respectively, p less than 0.05), (4) in T there was a correlation between the LMG and CSI, but not between the LML and CSI. In conclusion, lesions of the LM in the aged were generally mild and the LMG showed a positive correlation with CSI and the narrowing of each coronary branch, while no relationship was noted between the LML and CSI.

Aged↗

[Clinical effect of combined chemotherapy with UFT, MMC and OK-432 in recurring or advanced cancer of the digestive organs].

The usefulness of UFTMO therapy (combined chemotherapy with UFT, MMC and OK-432) performed in 40 cases of recurring or advanced cancer of the digestive organs was investigated. According the response criteria by Koyama et al., of 40 eligible cases, the treatment was judged effective in 13, 2 CR and 11 PR cases with a response rate of 32.5%, while of the 35 complete cases, 2 CR and 9 PR cases made for 11 effective cases and a response rate of 31.4%. Side effects were observed in 58.3% of the 36 evaluated cases; of the subjective and objective side effects, however, none were serious enough to require cessation of administration, while stopping administration in the cases of abnormal laboratory findings resulted in rapid recovery. UFTMO therapy, therefore, is considered to be one of the beneficial treatments for recurring or advanced cancer of the digestive organs.

Adult↗

[The effect of a selective 5-lipoxygenase inhibitor, AA-861 on airway hyperresponsiveness induced by ozone exposure in dogs].

To determine whether 5-lipoxygenase products are involved in hyperresponsiveness induced by ozone exposure, we studied the effect of a selective 5-lipoxygenase inhibitor, AA-861 on ozone-induced airway hyperresponsiveness in six dogs. Airway responsiveness to methacholine was measured by modified Astograph (7 Hz oscillation method) before and after ozone exposure, and TxB2 in plasma and in BALF, 6-keto-PGF1 alpha in BALF, numbers of neutrophils in the peripheral blood and differential cell counts in BALF were measured before and after ozone exposure. Ozone exposure was carried out for 2 hr at an ozone level of 3.04 +/- 0.01 ppm (mean +/- SE). There was a significant increase in airway responsiveness to methacholine after ozone exposure in the six dogs (p less than 0.01), and the numbers of neutrophils in the peripheral blood and the neutrophil counts in BALF increased significantly after ozone exposure (P less than 0.01). A selective 5-lipoxygenase inhibitor, AA-861 significantly inhibited the increase of airway responsiveness to methacholine induced by ozone exposure (p less than 0.05), and furthermore, the increase in the numbers of neutrophils in the peripheral blood and the neutrophil counts in BALF after ozone exposure were significantly inhibited by pretreatment with AA-861 (p less than 0.05). There was no significant change in the levels of TxB2 in plasma or in BALF, and also no apparent change in the levels of histamine was observed in BALF after ozone exposure. The levels of 6-keto-PGF1 alpha in BALF decreased after ozone exposure, but the decrease was not significant. These results suggest that 5-lipoxygenase products play an important role in the development of airway hyperresponsiveness and in the infiltration of neutrophils into the airway after ozone exposure in dogs.

Animals↗

[Adenoid cystic carcinoma presenting as cavernous sinus syndrome: a clinico-pathological study of two cases].

Adenoid cystic carcinoma (ACC), usually arising in the major and minor salivary glands, is well known to otolaryngologists, but is rarely encountered by neurologists or neurosurgeons. We report two ACC patients who presented initially with cavernous sinus syndrome and in whom CT did not demonstrate apparent abnormalities. Case 1 is a 48-year-old man who first developed right cavernous sinus syndrome. The patient came to our hospital four years later. At this time, the only abnormality found on CT was the clouded sphenoid sinus on the left, which was interpreted as sinusitis. Two years later, the repeat CT revealed the enhancing lesions in the area of bilateral cavernous sinuses with bony destruction. The nasolaryngological exploration of the left sphenoid sinus made the diagnosis of ACC. Case 2 is a 43-year-old man who developed unilateral cavernous sinus syndrome over three months. No radiological abnormality was apparent to the neurologist and neurosurgeons, however, the otolaryngologist detected a nasopharyngeal mass diagnosed as ACC. Histological examinations of the biopsy specimen from both cases revealed mixed cribriform, tubular, and solid patterns characteristic of ACC. Electron microscopic study in Case 1 demonstrated microvilli-containing epithelial tumor cells forming true glandular lumens. In these cystic spaces there were cellular debris and crystalloids consisting of hexagonally-arranged tubules with a diameter of 25 nm. Although thick basement membrane was found in the basal portion of the tumor cells facing the connective tissue, there was no so-called pseudocysts lined by replicated basal lamina. It is possible that the specimen examined electron microscopically is limited to a particular epithelial region.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗