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Biomedical subjects

Y Takada

Publications and source records attributed to Y Takada.

At least 469 records · Page 26Linked to original sources

Cloning of large DNA fragments, which hybridize with actinorhodin biosynthesis genes, from kalafungin and nanaomycin A methyl ester producers and identification of genes for kalafungin biosynthesis of the kalafungin producer.

Large actI, III-homologous DNA fragments were isolated from genomic libraries of the strains that produce the benzoisochromanequinone antibiotics kalafungin and nanaomycin A methyl ester, Streptomyces tanashiensis strain Kala and Streptomyces sp. OM-173, respectively. These libraries were prepared in Escherichia coli JM108 by using a novel Streptomyces-E. coli bifunctional cosmid, pKU205, and screened with polyketide synthase genes (actI and III) for actinorhodin biosynthesis from Streptomyces coelicolor A3(2) as probes. The cloned DNA fragments (28 and 42 kb) were analyzed by hybridization with DNA containing actinorhodin biosynthetic genes (actI, II, III, IV, VA, VB, VI and VII). Both fragments hybridized with the actI, III, VA and VI regions, but not with the actII, IV, VB and VII regions. The cloned fragment of S. tanashiensis DNA was analyzed by complementation tests with kalafungin-nonproducing mutants. Seven genes (kalI approximately VII), which correspond to seven steps in kalafungin biosynthesis, were found to be located on a 14 kb continuous DNA fragment. Five of the genes were located on the regions homologous to the genes for actinorhodin biosynthesis, but the other two genes were not. Although kalafungin is an intermediate or shunt product in actinorhodin biosynthesis in S. coelicolor A3(2), the genes for kalafungin biosynthesis in S. tanashiensis are not identical with those in S. coelicolor A3(2).

Anthraquinones↗

[Small sized non-small cell lung cancer in advanced stage].

Eighteen cases of non-small cell, small sized advanced lung cancer, out of 362 operated cases for 6 years excluding 7 cases of small cell lung cancer, 60 of preoperative treated and 27 of inoperable cases, were discussed. A small sized tumor was defined as a tumor within 8,000 mm3 in its volume, calculated by multipling three lengths measured on the resected specimens. There were fourteen cases with stage 3 and 4 (A), and four cases with N1 disease (B). In group A, three cases of twelve with N2 diseases showed the tiny skipping lesion in the mediastinum with negative regional nodes. Remaining two had a lesion of dissemination and pulmonary metastasis. In group B, they showed unusual way of N1 spread, in which two of them with left upper lobectomy had metastatic lymph nodes on the non-bearing lobe, the lower lobe, and other two cases took regional lymph nodes metastasis without invasive growth of the main tumor. Predominant histologic type was adenocarcinoma, but the subtype and the differentiation of it were not specific. The level of CEA was low below 5 ng/dl in most of them except three cases, in which it suggested massive positive nodes and pulmonary metastasis. Seven patients died of the disease in two years. Remainders are alive, 4 with and 7 free from the tumor with the longest period of 3 years and a half. N2 diseases of small sized tumor were found in the cases with the volume of 3 cm3 and more at almost same ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Correlation between plasma levels of ACTH and cortisol in basal states and during the CRH test in normal subjects and patients with hypothalamo-pituitary disorders.

Using a new ACTH-immunoradiometric assay (IRMA), we measured plasma ACTH levels in the basal states and during CRH test in normal subjects and the patients with hypothalamo-pituitary disorders. The basal levels of plasma ACTH in 76 normal young (25-45 yr) and 140 elderly (60-85 yr) subjects were 23.1 +/- 13.6, and 17.5 +/- 11.2 pg/ml, respectively. The plasma ACTH levels were less than detection limit (5 pg/ml) in 3 patients with isolated ACTH deficiency, and less than 10 pg/ml in 6 of 7 patients with hypopituitarism. A significant correlation was observed between the basal levels of plasma ACTH and of cortisol in two age groups, with almost the same regression line, showing no age-related decline in the plasma levels of ACTH and cortisol. In 2 normal subjects and 2 patients with Cushing's disease, synchronized secretions of ACTH and cortisol were observed between 0800h and 1800h. In normal subjects and the patients with pituitary disorders, a significant correlation was observed between the Area Under the Curve's for plasma ACTH and cortisol during the CRH test. The correlation constant was higher in normal subjects, but lower in the patients with acromegaly, non-functioning pituitary tumor, and Cushing's disease in this order, suggesting low sensitivity of the pituitary-adrenal axis in these patients. These results suggest that the ACTH-IRMA kit provide reliable data for clinical investigation, and that the secretions of ACTH and cortisol correlate each other in basal states and during the CRH test in the patients with pituitary disorders as well as in normal subjects.

Adolescent↗

Characterization of a new human apolipoprotein A-I Yame by direct sequencing of polymerase chain reaction-amplified DNA.

A new genetic variant apolipoprotein (apo), A-I Yame, was discovered during screening for apoA-I genetic variants with isoelectric focusing gel electrophoresis. To investigate the structural abnormality of apoA-I Yame, we amplified the apoA-I gene isolated from the proband's peripheral blood leukocytes with the polymerase chain reaction (PCR) method and directly sequenced these PCR fragments. ApoA-I Yame was found to have aspartic acid (GAC) substituted by tyrosine (TAC) at residue 13. We also identified this substitution by an automated DNA sequencer. This substitution was confirmed with amino acid sequencing of the isolated apoA-I Yame by Immobiline gel electrophoresis. This combined method, direct PCR from genomic DNA-derived individual peripheral blood leukocytes and subsequent direct sequencing, can be used to identify the entire sequence of apoA-I in a short period of time. Furthermore, with this method, it is possible to identify both alleles in heterozygous individuals.

Alleles↗

[A case of metoclopramide-induced neuroleptic malignant syndrome with cerebrospinal fluid lactic acidosis].

A case of metoclopramide-induced neuroleptic malignant syndrome with cerebrospinal fluid (CSF) lactic acidosis was reported. A 44-year-old Japanese woman noted tarry stool on July 2, 1988 and was treated with metoclopramide and cimetidine for nausea and vomiting. Hydroxyzine pamoate was also administered for insomnia at 3:10 am and she became comatose with muscle rigidity at 3:40-4:30 am on July 3. Tachycardia and high fever (39.5 degrees C) were evident at 8:00 am on July 4. She was transferred to the Kyushu University Hospital. On admission, serum creatine kinase was elevated to 1640 IU/1; MM fraction was 100%. She was diagnosed as malignant syndrome. Cerebrospinal fluid was normocellular with protein 38 mg/dl and glucose 122 mg/dl. Cerebrospinal fluid lactate increased markedly to 3.43 mmol/l, CSF pH was 7.264, HCO3- 14.4 mEq/l, indicating CSF metabolic acidosis. She became afebrile after the 10th hospital day, and gradually but completely recovered within a month. She was discharged on August 16, 1988. The anti-dopaminergic activity of metoclopramide was considered to be primarily responsible for the development of malignant syndrome in this case. Cerebrospinal fluid lactic acidosis seemed to reflect hyperpyrexia or malignant syndrome induced derangement of the brain metabolism.

Acidosis, Lactic↗

[A case of squamous cell carcinoma of the thymus and thymic cyst].

A 57-year-old man was referred to our hospital for further evaluation of an abnormal mediastinal shadow detected on chest X-ray film. Chest CT showed a solid mass and a cyst. Operation revealed a squamous cell carcinoma of the thymus adjacent to a thymic cyst. Histologic examination demonstrated the clear separation of the squamous cell carcinoma and the thymic cyst by interstitial tissue. Cases of squamous cell carcinoma of the thymus combined with thymic cyst are very rare.

Carcinoma, Squamous Cell↗

Hepatomuscular failure in septic catabolism: altered muscular response to plasma proteolytic factor in decreased hepatic mitochondrial redox potential.

To estimate the contribution of muscle protein in whole-body protein catabolism, the muscular contribution index (MCI; urine 3-methylhistidine/urine total nitrogen) was determined in 49 cases of elective laparotomy, together with the arterial blood ketone body ratio (KBR; acetoacetate/beta-hydroxybutyrate), which reflects hepatic mitochondrial redox potential. MCI increased after operation and the occurrence of severe infection, provided KBR was maintained above 0.7. In patients with sepsis, however, MCI decreased dependently with KBR (n = 33; p less than 0.01). In these patients, plasma proteolysis-inducing activity determined by in vitro bioassay increased in inverse proportion to KBR (n = 20, p less than 0.01). Moreover, plasma concentrations of not only aromatic but also branched-chain amino acids markedly increased when KBR decreased to below 0.4 (n = 23; p less than 0.05). Thus the role of muscle protein in septic catabolism is diminished under reduced hepatic mitochondrial redox potential, despite the rapid increase of proteolysis-inducing activity. This finally leads to the failure of amino acid uptake by muscles, as well as liver. These results suggest that the deteriorated substrate exchange may form the metabolic background for multiple systems organ failure, which is often preceded by reduced KBR.

Biomarkers↗

[The usefulness of diving reflex--the effect on PSVT].

We attempted to use the diving reflex to treat PSVT in five patients, in whom carotid-sinus massage had failed to terminate, PSVT. In three cases PSVT converted to normal sinus rhythm. The patient was seated comfortably, and a pan of ice and water (4 degrees C) was placed on the table in front of the patient. He then took a deep breath and, without expiration, submerged his face in the cold ice and water for about 30 seconds. In case 1, a 68-year-old male, PSVT stopped after facial immersion of 11 seconds. Subsequently, sinus arrest with junctional or ventricular contractions continued for 7 seconds followed by conversion to the sinus rhythm. The duration of facial immersion was 18 seconds. In case 2, a 51-year-old male, PSVT converted to the sinus rhythm in the same way. The duration of facial immersion was 23 seconds. Case 3 was a 27-year-old female with WPW syndrome. PSVT converted to the sinus rhythm after a 6.6 seconds facial immersion. Case 4 and 5 were respectively 72 and 73-year-old males, whose attacks did not respond to the diving reflex for the reason that they could not maintain breath-holding for a sufficient time to activate the reflex adequately. We postulated that apnea might effect the termination of PSVT in case 1 and 2 because relatively long duration of about 20 seconds was necessary to convert PSVT to the sinus rhythm. On the other hand, in case 3, cold water stimulation on the face might play an important role because PSVT converted to the sinus rhythm immediately.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Multiple ligand binding functions for VLA-2 (alpha 2 beta 1) and VLA-3 (alpha 3 beta 1) in the integrin family.

In our studies of VLA-3 we have shown (i) that a single integrin (VLA-3) can bind to multiple ligands by different mechanisms, involving RGD and non-RGD sites, which are regulated differently by divalent cations. Also we showed from the primary sequence of VLA-3 that it is only distantly related to the other cleaved alpha subunits. In our studies of VLA-2 we have shown that a single integrin may have at least three functional forms, depending on the cell type where expressed. In addition, we have expressed functional VLA-2 in RD cells, resulting in both Coll and Lm binding functions in vitro, and increased tumor cell metastasis in vivo in nude mice.

Amino Acid Sequence↗

Application of an interleukin 2 slow delivery system to the immunotherapy of established murine colon 26 adenocarcinoma liver metastases.

We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 minipellet, using a murine hepatic metastasis model. The IL-2 minipellet consists of atelocollagen derived from natural bovine skin together with 1 x 10(6) units of recombinant IL-2. Administration of the IL-2 minipellet was performed into the spleens of BALB/c mice after translocation of the spleens to the s.c. position. Administration produced detectable serum IL-2 levels for 72 h. The IL-2 minipellet was evaluated for its efficacy against hepatic metastases from colon 26 adenocarcinoma in the BALB/c mice. Both the administration of the IL-2 minipellet alone and its combination with the injection of 5 x 10(7) lymphokine-activated killer cells resulted in significant reductions of the number of metastatic nodules. Moreover, increased survival of mice bearing colon 26 adenocarcinoma was noted in these two treatment groups. To investigate the mechanism of the IL-2 minipellet activity, we tested the lytic potential of splenocytes obtained after administration of the IL-2 minipellet in a 51Cr release assay. Cytotoxicity against YAC-1 cells and colon 26 cells was significantly augmented on Day 2 after minipellet administration. These results demonstrated that local administration of the IL-2 minipellet into the hepatic circulation was extremely effective against metastatic liver cancer.

Adenocarcinoma↗

[Evaluation of delayed I-123 IMP lung studies in atelectatic and inflammatory diseases in comparison with Ga-67-citrate scintigraphy].

We have previously reported that increased tracer accumulation on delayed 123I-IMP scintigraphy is associated with atelectasis and inflammation. The purpose of this study was to evaluate the diagnostic values of delayed 123I-IMP lung scintigraphy, compared with gallium scintigraphy. Ten patients with atelectasis caused by lung cancer and 7 patients with inflammatory diseases were studied. Inflammatory lung disease included 4 cases of pneumonia, 2 of interstitial pneumonitis, and 1 of diffuse panbronchiolitis. Delayed 123I-IMP scintigraphy was performed 24 hours after intravenous injection of 111 MBq of 123I-IMP. In 14 patients, the SPECT images were obtained. Gallium scintigraphy was done within 7 days of 123I-IMP scintigraphy and the images were obtained 72 hours after the administration of 111 MBq of 67Ga-citrate. 123I-IMP scintigraphy was compared with gallium scintigraphy for its ability to detect atelectasis. The degree of uptake by the collapsed lobes was judged visually on planar images and rated using four grades: negative, slight, moderate and heavy. All the cases showed moderate or intense uptake on the 123I-IMP images, whereas with gallium scintigraphy there was no change corresponding with lobar collapse in 8 out of 10 cases. Of the remaining 2 cases, one had tumor in the collapsed lobe and the other had obstructive pneumonia. In inflammatory lung diseases, the correlation of 123I-IMP and gallium images regarding degree of change shown on chest X-ray film was studied. The degree of correlation was classified using four grade: poor, fair, good and excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Fluctuation of tPA and PAI-1 antigen levels in plasma: difference of their fluctuation patterns between male and female.

The circadian fluctuation of the fibrinolytic activity and the antigen levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in plasma were analyzed in normal male and female volunteers. Samples were obtained at 8:30, 10:30, 12:30, 14:30 and 16:30 h. Euglobulin clot lysis time (ECLT) showed the longest time at 8:30 to 10:30 h and the shortest time at 16:30 h. The highest level of tPA was obtained at 8:30 h and the lowest at 14:30 h in men, whereas the highest value was at 8:30 h and the lowest was at 16:30 h in females. Free PAI-1 showed highest value at 10:30 h in men and at 8:30 h in women. The lowest values obtained at 16:30 h in both men and women and were about one third of the highest values. ECLT was always shorter in females than in males and parameter such as tPA and PAI-1 were also lower in females than in males. The phase of the circadian rhythm of the fibrinolytic parameters may be advanced in females than in males.

Adolescent↗

Fluctuation of TPA and PAI-1 antigen levels in plasma: difference of their fluctuation patterns between male and female.

The daytime fluctuation of the fibrinolytic activity and the antigen levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in plasma were analyzed in normal male and female volunteers. Samples were obtained at 8:30, 10:30, 12:30, 14:30 and 16:30 h. Euglobulin clot lysis time (ECLT) showed the longest time at 8:30 to 10:30 h and the shortest time at 16:30 h. The highest level of tPA was obtained at 8:30 h and the lowest at 14:30 h in men, whereas the highest value was at 8:30 h and the lowest was at 16:30 h in females. Active free PAI-1 showed highest value at 10:30 h in men and at 8:30 h in women. The lowest values obtained at 16:30 h in both men and women and were about one third of the highest values. ECLT was always shorter in females than in males and parameter such as tPA and PAI-1 were also lower in females than in males. The phase of the circadian rhythm of the fibrinolytic parameters may be advanced in females than in males.

Adolescent↗