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Biomedical subjects

T Naito

Publications and source records attributed to T Naito.

At least 235 records · Page 13Linked to original sources

Disseminated adenovirus (type 19) infection in a neonate. Rapid detection of the infection by immunofluorescence.

A case of fatal disseminated adenovirus infection in a neonate who suffered from severe keratoconjunctivitis and pneumonitis is reported. The diagnosis was made seven days after the onset of illness based on the detection of adenovirus antigen in the smears of the tracheal suction and conjunctival swab by immunofluorescence. Viral antigen was detected in the frozen or formalin-fixed autopsy specimens of the lungs, kidneys, spleen, liver and lymph nodes. Typical crystal arrangement of adenovirus virions was observed in the alveolar epithelial cells by electron microscopy. The isolated virus was identified to be of type 19 by a neutralization test. The IF examination using adenovirus group specific immune reagents on the smears of clinical specimens appears to be useful for rapid diagnosis of viral infections.

Adenoviridae Infections↗

Intracranial hemorrhage associated with nontraumatic disseminated intravascular coagulation--report of four cases.

The authors report four cases of intracranial hemorrhage associated with nontraumatic disseminated intravascular coagulation (DIC). Two cases demonstrated a sudden onset of intracerebral hemorrhage. The other two showed chronic subdural hematoma initially, followed by acute multiple intracranial hemorrhages or general hemorrhagic diathesis. The underlying disorders were glioblastoma multiforme, thoracoabdominal aortic aneurysm, acute promyelocytic leukemia, and stomach cancer associated with disseminated carcinomatosis of the bone marrow. All patients died eventually. When the underlying disorder has a rare incidence of DIC as in glioblastoma multiforme or thoracoabdominal aortic aneurysm, the possibility of DIC and the need for immediate initiation of replacement therapy should be recognized, although the mortality is very high because the underlying disorder cannot be eliminated quickly. When the underlying disorder has a high incidence of DIC as in acute promyelocytic leukemia or disseminated carcinomatosis of the bone marrow, it is mandatory to start replacement therapy and treatment for the underlying disorder simultaneously. DIC can be controlled when the treatment for the underlying disorder is effective.

Adult↗

Antiproliferative activity of mammalian lignan derivatives against the human breast carcinoma cell line, ZR-75-1.

The effect of each of twelve mammalian lignan derivatives on the growth of human mammary tumor ZR-75-1 cells was examined. At a concentration less than 10 micrograms/ml, tumor cell growth was inhibited from 18-68%. The effect of 2,3-dibenzylbutane-1,4-diol(hattalin) was found to be strongest, inhibiting growth by 50% at a concentration (EC50) of 2.1 micrograms/ml. Hattalin inhibited membrane Na+, K(+)-ATPase of canine kidney cortex. It also inhibited the ATPase of the plasma membrane fraction from both cultured cells and a section of human breast cancer tissue at a concentration ranging from 0.5 to 2.0 mM. However, only a few percent of membrane ATPase from either ZR-75-1 cells or breast carcinoma tissue was inhibited by 2.0 mM of ouabain, suggesting that the target ATPase of hattalin was other than ouabain-sensitive ATPase. The relative incorporation of [3H]thymidine per 1 x 10(5) cells into the acid-precipitable fraction of ZR-75-1 cells was not affected by 1-50 micrograms/ml of hattalin, while a marked decrease resulted from 1-10 micrograms/ml of 5-fluorouracil (5-FU). These results suggest that the suppressive effect of hattalin on tumor cell growth may not occur through inhibition of DNA synthesis but rather partly by inhibition of the plasma membrane ATPase other than Na+ and K(+)-dependent ones.

4-Butyrolactone↗

Improved synthesis of an ester-type prodrug, 1-acetoxyethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-[(Z)-1- propenyl]-3-cephem-4-carboxylate (BMY-28271).

1-Acetoxyethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3- [(Z)-1-propenyl]-3-cephem-4-carboxylate (BMY-28271) is an ester-type prodrug of cephalosporin for oral use. Methods suitable for large scale preparation were investigated. The yield was improved by esterification of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-trityloxyiminoacetamido]cep hem-4-carboxylic acid (11) followed by removal of the trityl group and, in addition, column chromatographic purification at each step was eliminated by optimization of the reaction conditions.

Acylation↗

Synthesis of a new series of cephalosporins having 3-substituted-ammonio-1-propenyl group as the C-3 side chain.

The synthesis and antimicrobial activity of eight derivatives of 7-[(Z)-2-(2-aminothiazol-4-yl)- and 7-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido] cephalosporins having an (E) or (Z)-3-ammonio-1-propenyl group in the C-3 side chain are described. The (E)-propenyl derivatives were more active than their corresponding Z-isomers and showed well-balanced, broad antibacterial activity against both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa.

Bacteria↗

Direct introduction of a formamido group into the 7 alpha (6 alpha)-position of cephalosporins (penicillins).

A novel direct introduction of a formamido group into the 7 alpha (6 alpha)-position of cephalosporins (penicillins) was achieved by treatment of 7 beta (6 beta)-[(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1- ylidene)methylimino]cephem (penam) esters with N,N-bis(trimethylsilyl)formamide, followed by deblocking with Girard reagent T to give the corresponding 7 alpha (6 alpha)-formamido-7 beta (6 beta)-amino derivatives. Three 7 alpha-formamidocephalosporins were prepared by the conventional N-acylation of 7 alpha-formamidocephem. All of them were resistant to beta-lactamases, showing similar MIC values against both of a pair of a beta-lactamase-producing strain and the corresponding non or low-producing strain of the same species of bacteria, when tested on Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Enterobacter cloacae and Citrobacter freundii.

Bacteria↗

Amikacin analogs with a fluorinated amino acid side chain.

The synthesis and biological activity of kanamycin A derivatives with an omega-amino-alpha-fluoroalkanoyl side chain on the 1-amino group are described. The fluorinated amino acids (4) for the side chain were prepared by fluorination of the alpha-hydroxy esters (2) with diethylaminosulfur trifluoride (DAST) with accompanying the Walden inversion. The reaction products varied with the amino protective groups employed, chain length of the alkanoic acids and the presence or absence of base. The fluorinated side chain was introduced to 1-free-NH2 kanamycin A (12) by the conventional active ester method and subsequent deblocking reactions afforded the desired final products (13-17). Of the derivatives prepared, 1-N-[(S)-4-amino-2-fluorobutyryl]kanamycin A (2'''-deoxy-2'''-fluoroamikacin, 14) showed the best overall activity profile, nearly the same as that of amikacin. Preparation and antibacterial activity of several aminoglycoside antibiotics with the 1-N-(S)-4-amino-2-fluorobutyryl side chain are also discussed.

Amikacin↗

Effects on herpes simplex virus type 1 of combined use of interferon-beta and anti-herpetic agents in vitro.

It has been shown that the use of interferon (IFN) alone has little or no therapeutic effect in the treatment of herpetic keratitis. However, IFN used in combination with anti-herpetic agents has high therapeutic efficacy. This interaction between IFN and anti-herpetic agents has not been elucidated clearly. In this study, the interaction between human fibroblast interferon (HuIFN-beta) and anti-herpetic agents, 5-iodo-2'-deoxyuridine (IDU), aciclovir (ACV) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), was studied in vitro using VERO cells. After the formation of a monolayer of VERO cells, HuIFN-beta of various concentrations was added to the maintenance medium. After 24 hours incubation, the medium was removed and herpes simplex virus (HSV) type 1 was inoculated on the VERO cells. Then, anti-herpetic agents were added to the medium in various concentrations. After 48 hours incubation, plaques were counted and the reduction rate in numbers of plaque was calculated. It was found that the combination of HuIFN-beta with IDU, ACV or DHPG worked synergistically in the inhibition of HSV replication.

Acyclovir↗

Highly selective synthetic inhibitors with regard to plasma-kallikrein activities.

The synthetic inhibitors of plasma kallikrein (PK) were found, which are called PKSI-1007, PKSI-0180 and PKSI-0527 in our laboratories. (1) The inhibitors inhibited PK competitively with D-Pro-Phe-Arg-pNA and the Ki values obtained were considerably small, 10(-6) M-10(-7) M. However, the Ki values for glandular kallikrein (GK), plasmin (PL), thrombin (TH) and factor Xa (FXa) were larger. In particular, a selectivity of PKSI-0527 towards PK was very high and the toxicity was weak (i.v. LD50 for mice is over 100 mg/kg). (2) The inhibitors were effective (a) to prevent the bradykinin formation in the kaolin-activated human plasma and the acid-treated ascites taken from the mice bearing Sarcoma 180, (b) to prolong the coagulation time by contact activation, and (c) to inhibit the enhancement of ADP-platelet aggregation by PK. The results indicated that the some PKSI-inhibitors will be much useful for the basic studies, furthermore they deem to be even promising towards the clinical application.

Amino Acid Sequence↗

Nature of renal involvement in the acro-renal-ocular syndrome.

A 16-year-old female with acro-renal-ocular syndrome complicated by ventricular septal defect is described. Renal biopsy was performed for the first time in this syndrome, and the results suggested that proteinuria and renal dysfunction were caused by chronic pyelonephritis secondary to malrotation of the kidney and anomalous pelves. Chronic renal failure and hypoplasia of the optic papillae were also observed in the patient's mother, suggesting a participation of heredity in the pathogenesis of the syndrome.

Adolescent↗

Synthesis of tripeptide chloromethyl ketones and examination of their inhibitory effects on plasmin and plasma kallikrein.

With the aim of obtaining selective synthetic inhibitors of plasmin and plasma kallikrein, D-Ile-Phe-Lys-CH2Cl, Ile-Phe-Lys-CH2Cl, D-Ile-Phe-Arg-CH2Cl and Ile-Phe-Arg-CH2Cl were synthesized and their inhibitory activity against plasmin, plasma kallikrein and other trypsin-like serine proteinases was examined. Among them, D-Ile-Phe-Arg-CH2Cl exhibited a highly selective inhibitory activity against plasma kallikrein, yet D-Ile-Phe-Lys-CH2Cl exhibited nearly the same order of inhibitory activity against plasmin as well as plasma kallikrein.

Amino Acid Chloromethyl Ketones↗

Relationship between milk composition and pup's growth in mice.

The effect of lactation numbers (first, second, and third) on milk composition and the relationship between milk composition and pup's growth were examined in four strains of mice (SHN, SLN, C3H/He, and GR/A). Although the percentage of milk fat and moisture increased and decreased, respectively, through the first to third lactations in C3H/He mice, no differences in milk composition among lactation numbers were observed in the other mouse strains. In pooled data derived from the four strains of mice, there was no significant correlation between milk composition and body weight or growth rate of pups on Day 12 or 20 of the first lactation. In contrast, the amount of milk fat and moisture was the positively and negatively, respectively, correlated with the pup's growth parameters during the second and third lactations. This was reflected by a lower fat content and a higher moisture content in the milk of GR/A mice, especially evident during the second and third lactations and reduced pup's growth, when compared with the other mouse strains. Milk lactose and ash content was not correlated with pup's growth parameters. The results of our study stress the importance of milk fat for the growth of mouse pups.

Animals↗

New cirramycin-family antibiotics F-1 and F-2. Selection of producer mutants, fermentation, isolation, structural elucidation and antibacterial activity.

Two new 16-membered macrolides, cirramycins F-1 and F-2, were isolated from the culture filtrate of a mutant strain B-1425 of Streptomyces cirratus JTB-3. The antibiotics were also produced by bio-transformation of cirramycin A1 using a blocked mutant strain A-0033. Structures of F-1 and F-2 have been elucidated by spectral interpretation and analysis of acid degradation products. Both involved isomeric modification of a neutral sugar; F-1 contained L-rhodinose, and F-2 L-amicetose. Based on spectral data, cirramycin F-1 and antibiotic A6888C were found to be identical. Cirramycins F-1 and F-2 are active against Gram-positive bacteria, but less active than cirramycin A1.

Anti-Bacterial Agents↗

Inactivation of erythrocyte Cu-Zn-superoxide dismutase through nonenzymatic glycosylation.

Human erythrocyte Cu-Zn-superoxide dismutase undergoes glycation reaction in vitro and in vivo (Arai et al., 1987a; Arai et al., 1987b). In addition, an increase in the glycation of the superoxide dismutase was observed in aged erythrocytes, indicating that the glycation reaction is an age-related change under physiological conditions. In the cases of crude extracts as well as pure enzyme preparations obtained from erythrocytes of patients with Werner's syndrome, the specific activity of the glycated form expressed as units per mg Cu-Zn-superoxide dismutase protein as determined by both enzymatic assay and immunoenzymatic assay was significantly lower and the enzyme was unstable as compared to the normal form.

Adult↗

[Aberrant expression of major histocompatibility complex class II. (HLA-DR/DQ) antigens and proliferative nuclear antigen. (Ki-67) in renal tubular epithelial cells].

In an attempt to clarify the participations of cellular immunity in the development of tubulo-interstitial lesions, aberrant expressions of major histocompatibility complex (MHC) class II antigens and Ki-67 nuclear antigen on the renal tubular epithelial cells were studied. Ki-67 antigen was known to appear in all phases of cell cycle except for Go. Nine normal kidney specimens (4 males and 5 females) and 117 kidney specimens obtained from patients with kidney diseases (54 males and 63 females) were examined with the indirect immunofluorescence technique using murine monoclonal antibodies against HLA-DR (lal), HLA-DQ (Leu10) and Ki-67 nuclear antigen. Patients included 100 with glomerular diseases, and 16 with tubulo-interstitial diseases consisting of 4 acute tubular necrosis (ATN), 7 acute tubulo-interstitial nephritis (AIN), one renal allograft rejection and 4 sarcoidosis. In normal kidney, HLA-DR was solely noted in only two specimens (22.2%) at the basal portion of proximal tubular epithelial cells. In tubulo-interstitial diseases 11 (68.8%) out of 16 patients showed diffuse and intense expressions of HLA-DR concomitant with HLA-DQ in 6 of 13 (42.9%), and 11 of 13 (84.6%) were positive for Ki-67 nuclear antigen. Especially, in AIN and allograft rejection, intense expression of HLA-DR, DQ and Ki-67 nuclear antigen were observed in 100%, 86%, 100%, respectively. In ATN 3(75%) were positive for HLA-DR and Ki-67, but not for HLA-DQ. In contrast, only 12(15.6%). 2(2.6%) and 2(4.8%) of primary glomerular disease were weakly positive for HLA-DR, DQ and Ki-67 nuclear antigen, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[The motility of lung lymphocytes in hypersensitivity pneumonitis and sarcoidosis].

Hypersensitivity pneumonitis (HP) and pulmonary sarcoidosis (Sa) are characterized by an accumulation of large numbers of lymphocytes within the interstitium and the epithelial surface of the lung. Although the lymphocytes in bronchoalveolar lavage fluid (BALF) are representative of interstitial cells in these diseases, the mechanism involved in an accumulation of lymphocytes on the epithelial surface are yet unknown. To explore the possibility that the lymphocytes on the epithelial surface are migrated cells from the interstitium, we studied the motility of the BALF lymphocytes in five patients with HP and nine patients with Sa and compared them to that of peripheral blood lymphocytes. The lymphocyte migration assay was performed using blind well chemotaxis chambers and cells migrated into the cellulose nitrate membranes were assessed. The total migrated cell numbers of BALF lymphocytes in HP and Sa were 753.3 +/- 86.5 and 334.2 +/- 41.0, respectively. The migration distance of BALF lymphocytes in HP and Sa assessed with leading front method were 50.2 +/- 3.8 microns and 57.9 +/- 4.6 microns, respectively. The motility of BALF lymphocytes in HP and Sa was significantly greater than that of peripheral blood lymphocytes and the motility of BALF lymphocytes were comparable to that of PHA-activated lymphocytes. The motility of BALF lymphocytes were correlated with the proportion of lymphocytes in BALF cells and the proportion of Ia+T lymphocytes. These results suggest that BALF lymphocytes in these diseases are activated and enhanced motility may facilitate the accumulation of lymphocytes to the epithelial surface.

Alveolitis, Extrinsic Allergic↗

Surfactant replacement therapy in neonatal respiratory distress syndrome. A multi-centre, randomized clinical trial: comparison of high- versus low-dose of surfactant TA.

We conducted a prospective, randomized, controlled trial comparing the efficacy of two doses of a reconstituted bovine surfactant (Surfactant TA) in premature infants requiring mechanical ventilation shortly after birth for respiratory distress syndrome. Forty-six infants weighting 1000-1499 g were randomized into two groups: a low-dose group (23 infants given a single dose of 60 mg surfactant lipid/kg) and a high-dose group (23 infants given a single dose of 120 mg/kg). The mean (SD) age at which surfactant was given was 5.5 (+/- 1.2) h in the low-dose group and 6.0 (+/- 1.5) h in the high dose group. Both treatments improved oxygenation (increased arterial-alveolar PO2 ratio) with decreased mean airway pressure, the high-dose surfactant having a more beneficial effect in prolonging the response. Infants in the high-dose group had significantly less (P less than 0.05) incidence of both intraventricular haemorrhage and bronchopulmonary dysplasia. This prospective trial documents that a greater benefit can be obtained by increasing the dose of surfactant (120 mg/kg) beyond 60 mg/kg treatment of premature infants with severe respiratory distress syndrome (RDS).

Clinical Trials as Topic↗

Effects of pituitary grafting on plasma and milk levels of prolactin, growth hormone and progesterone in mice.

Plasma and milk levels of prolactin, growth hormone (GH) and progesterone on days 12-13 of lactation were compared between C3H/He female mice grafted with isologous anterior pituitaries each under the kidney capsules 2-3 days after placing with males and intact controls. At the 1st lactation, both plasma and milk levels of prolactin were higher in the experimental mice than in the control, however, at the 2nd lactation, milk prolactin level of the former decreased to about 1/8 of that of the latter, whereas plasma prolactin level further elevated in the former. While plasma GH level was increased by pituitary grafting, milk GH level was slightly affected by the treatment at either the 1st or the 2nd lactation. There was only a small difference between the experimental and the control groups in either plasma or milk level of progesterone at the 1st and the 2nd lactations. Progesterone levels in plasma and milk were higher at the 1st lactation than at the 2nd lactation in both the experimental and the control groups. These results suggest that the transfer of plasma hormones into milk is not always free, but there may be any regulatory mechanism(s) in this process.

Animals↗