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Biomedical subjects

F Kishi

Publications and source records attributed to F Kishi.

At least 73 records · Page 4Linked to original sources

Effect of aminophylline on brain tissue oxygenation in patients with chronic obstructive lung disease.

BACKGROUND: It is known that theophylline reduces cerebral blood flow in humans. To quantitatively assess the possible adverse effect of theophylline on brain tissue oxygen tension (PO2) due to decreased cerebral blood flow, two sets of experiments were conducted in mildly hypoxaemic patients with chronic obstructive lung disease. METHODS: Firstly, internal jugular venous PO2 (PjO2) was measured simultaneously with arterial and mixed venous blood PO2 (PaO2 and PvO2) during right heart catheterisation in 10 subjects (mean PaO2 73 mm Hg; conversion factor: 10 mm Hg = 1.33 kPa)) before and after intravenous infusion of aminophylline (6 mg/kg). The PjO2 and PvO2 were considered to reflect the average tissue PO2 for the brain and for the whole body respectively. Secondly, the relation between PaO2 and PjO2 over a wide range, with the PaCO2 similar to that in the first study, was investigated in a different group of 12 subjects by stepwise changes in inspiratory gas composition. RESULTS: The mean PjO2 decreased by as much as 6 mm Hg 15 minutes after an infusion of aminophylline, whereas PaO2 stayed at the same level and PvO2 showed only a small decrease. The low PjO2 value of 29 (SD 6) mm Hg with aminophylline in the first study was similar to the PjO2 value of 30 (2) mm Hg obtained during severe hypoxia (PaO2 45 mm Hg) in the second study. The coefficient of oxygen delivery for the brain decreased by 29% with aminophylline treatment, but did not change significantly during severe hypoxic challenge. CONCLUSIONS: These data suggest that an infusion of aminophylline lowers brain tissue PO2 appreciably when given to mildly hypoxaemic patients with chronic obstructive lung disease.

Aminophylline↗

Augmented heart rate response to hypoxia in patients with chronic obstructive pulmonary disease.

Effects of acute, progressive isocapnic hypoxia on heart rate (HR) and ventilation were determined in 31 patients with chronic obstructive pulmonary disease (COPD) and in 24 normal control subjects. There was an inverse linear relationship between heart rate and SaO2 in each subject. The slope factor (delta HR/delta SaO2) obtained from the regression line was significantly higher in the patients with COPD than in the normal control subjects (0.888 +/- 0.309 SD beats/min/% fall in SaO2 versus 0.693 +/- 0.287; p less than 0.05), whereas the ventilatory response (delta VE/delta SaO2) was not significantly different between the two groups. To elucidate factors responsible for the augmented heart rate response to hypoxia in the patients with COPD, we examined the relationships of delta HR/delta SaO2 with age, physical characteristics, pulmonary function data, and arterial blood gas data in all the subjects. A weak but significant relationship was found only between delta HR/delta SaO2 and FEV1/VC, %FEV1, RV/TLC, and %RV. Because the HR response to hypoxia correlates only with parameters that reflect the grade of airway obstruction, we believe that the enhanced HR response seen in patients with COPD is a result of the disease process in the airway and tissue, although the precise mechanism was not specified in this study.

Female↗

Squamous cell carcinoma antigen is a new member of the serine protease inhibitors.

We have cloned cDNA of squamous cell carcinoma antigen. Sequence analysis of the complete 1711 basepairs SCC antigen cDNA revealed that it coded 390 amino acids and no typical signal sequence in the NH2-terminus. Northern blot analysis of human squamous cell poly(A)+ RNA using this cDNA insert as the probe showed a single RNA species of about 1.7 kilobases. The cDNA was expressed in Escherichia coli and the product was detected by immunological methods using antibodies against SCC antigen, indicating that this cDNA encodes the entire SCC antigen sequence. The amino acid homology search revealed that SCC antigen was a member of the serine protease inhibitors family.

Amino Acid Sequence↗

Prenatal diagnosis of infantile hypophosphatasia.

Prenatal diagnosis was attempted in a pregnant Japanese woman whose son had died of infantile hypophosphatasia, using chorionic villi sampled at 10 weeks of gestation. Southern blot analysis of restriction fragment length polymorphism was used as a guide, with cDNA for the human liver-type alkaline phosphatase as a probe, and BclI as a restriction enzyme. The fetus was found to be a heterozygote; the pregnancy was allowed to continue; and the baby born was phenotypically normal.

Alkaline Phosphatase↗

Characterization of a processed pseudogene derived from the gene encoding bovine adenylate kinase isozyme 2.

We have isolated an intronless processed pseudogene for an isoform of bovine adenylate kinase isozyme 2 (AK2B). The pseudogene which was flanked by 11-nucleotide (nt) direct repeats contained an open reading frame of 519 bp which encodes 173 amino acids (aa), 61 aa shorter than AK2B. In the entire pseudogene sequence, substitutions as well as deletions and insertions were noted in 78 nt positions as compared with the AK2B cDNA (95.1% homology). Northern-blot analysis showed that this pseudogene was not expressed in bovine tissues.

Adenylate Kinase↗

Longitudinal analyses of respiratory chemosensitivity in normal subjects.

To evaluate relative contributions of inherent versus extrinsic factors to respiratory chemosensitivity, ventilatory responses to isocapnic progressive hypoxia and normoxic progressive hypercapnia were examined at intervals of 8 to 10 yr in 32 healthy male volunteers aged 42.2 +/- 1.4 yr (SEM) in the final examination. The volunteers included 22 sons of patients with chronic obstructive pulmonary disease. The mean value for the slope factor of the end-tidal PO2-ventilation hyperbola (A) significantly decreased from 98.3 +/- 12.2 to 77.4 +/- 10.3 L/min mm Hg (p less than 0.05), but that for the end-tidal PCO2 ventilation line (S) did not change over the years. The individual values for the hypoxic ventilatory response were significantly correlated (r = 0.63, p less than 0.001) between the initial and final examinations but not so for the hypercapnic ventilatory response (r = 0.23, NS), suggesting that the latter is more subject to influence from extrinsic factors than the former in the long term. The reproducibility of both tests expressed as coefficients of variation was similar or rather small for the hypercapnic ventilatory response, which was determined by three consecutive measurements at 1 wk intervals in a different group of six subjects. From these data we conclude that hypoxic chemosensitivity is more determined by factors inherent to the individual than hypercapnic chemosensitivity and that it is more systematically influenced by temporal factors, as demonstrated by the systematic decrease over the years.

Adult↗

[A case of chronic pulmonary emphysema with a past history of bilateral carotid body resection].

A 76-year-old man, whose carotid bodies had been resected for treatment of bronchial asthma 40 years previously was admitted for evaluation of abnormal arterial blood gases and exertional dyspnea. The case was diagnosed clinically as chronic pulmonary emphysema. His peripheral chemoreceptor function, estimated by hypoxic ventilatory and P0.1 response tests and withdrawal test was non-functioning. His PaCO2 value tended to rise over 50 Torr either after light exercise or during airway infection, though it was normal at rest. In addition his dyspnea had continued for 40 years in spite of carotid body resection. It was concluded that the effect of carotid body resection lasts more than 40 years and it does not have a good effect on COPD.

Aged↗

[Effects of antiplatelet serum on the pulmonary intravascular macrophage].

Antiplatelet serum (APS) has been used to investigate the role of platelets in lung injury. However, the effect of APS on pulmonary intravascular macrophages (PIMs) is unknown. Therefore we investigated the effects of APS on PIMs. A bolus injection of APS raised pulmonary arterial pressure with the production of thromboxane. Fluorescence- and electronmicroscopy revealed that PIMs engulfed APS-platelets complexes after the APS injection. Repeated injections of APS increased the ratio of PIMs which engulfed platelets and the number of platelets in a PIM, but attenuated phagocytosis of liposomes by PIMs to decrease liposome-induced pulmonary hypertension and production of thromboxane. From the above data it was concluded that APS injection causes PIMs to engulf APS-platelets complexes, and that APS injection attenuates the phagocytosis of liposomes by PIMs, and thereby diminishes liposome-induced pulmonary hypertension and production of thromboxane.

Animals↗

Isolation and characterization of the gene encoding bovine adenylate kinase isozyme 2.

Mitochondrial adenylate kinase isozyme 2 (AK2) exists in two isoforms, AK2A and AK2B, which have the same amino-acid sequence except for the C-terminal portion. We have isolated the gene encoding AK2 from a bovine genomic library. The gene covers about 25 kb and consists of seven exons and six introns. The nucleotide sequences from exon 1 to the 5' half of exon 6 encode the portion common to AK2A and AK2B, while the sequences of the 3' half of exon 6 and exon 7 direct the unique portions of AK2A and AK2B, respectively. Therefore, an alternative splicing mechanism is suggested in generating two types of mRNA encoding AK2A and AK2B. The 5'-flanking region of the gene lacks a TATA box, but contains three CAAT boxes. The G + C content of this region is high and eight copies of GC box are found. These features of the promoter region resemble those of 'housekeeping' genes. S1 mapping and primer extension analyses revealed multiple transcription start points. The 581-bp region just upstream from the start codon functions as a promoter in the expression of the cat gene in Chinese hamster ovary cells.

Adenylate Kinase↗

Characterization of a 5'-flanking region of the human liver/bone/kidney alkaline phosphatase gene: two kinds of mRNA from a single gene.

We have cloned the human liver/bone/kidney alkaline phosphatase (ALPL) gene using a liver-type ALPL cDNA as a probe. The gene is divided into 12 exons, and is likely to exist as a single copy in haploid genome. As compared with the gene isolated using a bone-type ALPL cDNA (Weiss et al., J. Biol. Chem. 263, 12002-12010, 1988), another leader exon specific for the liver-type ALPL mRNA was assigned about 3.4 kb upstream from exon 2 and the alternative splicing in the first exon was indicated. RNA blot analysis showed that three species of mRNA of 2.5, 4.1 and 4.7 kilobases were detected in liver and developmentally regulated.

Alkaline Phosphatase↗

Mechanism of adenylate kinase. Are the essential lysines essential?

Using site-specific mutagenesis, we have probed the structural and functional roles of lysine-21 and lysine-27 of adenylate kinase (AK) from chicken muscle expressed in Escherichia coli. The two residues were chosen since according to the nuclear magnetic resonance (NMR) model [Mildvan, A. S., & Fry, D. C. (1987) Adv. Enzymol. 58, 241-313], they are located near the alpha- and the gamma-phosphates, respectively, of adenosine 5'-triphosphate (ATP) in the AK-MgATP complex. In addition, a lysine residue (Lys-21 in the case of AK) along with a glycine-rich loop is considered "essential" in the catalysis of kinases and other nucleotide binding proteins. The Lys-27 to methionine (K27M) mutant showed only slight increases in kcat and Km, but a substantial increase (1.8 kcal/mol) in the free energy of unfolding, relative to the WT AK. For proper interpretation of the steady-state kinetic data, viscosity-dependent kinetics was used to show that the chemical step is partially rate-limiting in the catalysis of AK. Computer modeling suggested that the folded form of K27M could gain stability (relative to the wild type) via hydrophobic interactions of Met-27 with Val-179 and Phe-183 and/or formation of a charge-transfer complex between Met-27 and Phe-183. The latter was supported by an upfield shift of the methyl protons of Met-27 in 1H NMR. Other than this, the 1H NMR spectrum of K27M is very similar to that of WT, suggesting little perturbation in the global or even local conformations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Kinase↗

Isolation of a Y chromosomal DNA sequence and its clinical application.

A 4.6 kb long, Y-specific DNA fragment was isolated from a flow-sorted human Y chromosomal library, and its male specificity was confirmed by Southern blot analysis. The fragment, designated as pY-80, was proven with an in situ hybridization experiment to have originated from the Yp11.2-Ypter region. Its 2,808 bp section was sequenced. The polymerase chain reaction proceeded with oligonucleotides flanking a 666 bp PstI-EcoRI fragment of the sequence as primers and a male genomic DNA as a template, but not with a female genomic DNA. Preliminary tests of samples of various sources successfully detected the Y-specific fragment in male-derived samples, including mouth wash, single hair roots, urinary epithelial cells, dried blood spots and amniotic fluid cells.

Base Sequence↗

Naloxone increases ventilatory response to hypercapnic hypoxia in healthy adult humans.

The ventilatory response to hypercapnic progressive hypoxia and the breathing pattern during steady-state hypercapnic hypoxia were compared before and after intravenous infusion of 3 mg of naloxone in a relatively large number of healthy adults (n = 21). In addition, the withdrawal response from hypercapnic hypoxia (modified transient O2 test) was measured to investigate the possible role of endogenous opioids in the peripheral chemoreceptors. The average ventilatory response (delta VE/delta SaO2) increased significantly from 0.51 +/- SD 0.26 to 0.65 +/- 0.42 L/min/% (p less than 0.05) after naloxone infusion, whereas there were no significant changes between two tests with normal saline in the control study (n = 7). Because there was considerable interindividual variation in the response to naloxone administration, we selected "high responders" (n = 8) who showed larger increases with naloxone than the upper limit of the 95% confidence interval for the change with the second saline in the control study. They showed greater delta VE/delta SaO2 (p less than 0.01), respiratory frequency (p less than 0.01), and mean inspiratory flow (p less than 0.01) during hypercapnic hypoxia before naloxone infusion than did the other subjects. There was no significant change in the withdrawal response before and after naloxone infusion, even in such high responders. We conclude that endogenous opioids participate in the control of breathing in normal adults during hypercapnic hypoxia. This may be particularly true for those subjects who exhibit greater chemosensitivity to hypercapnic hypoxia. Endogenous opioids appear to act centrally rather than peripherally.

Adult↗

[Clinical and pathological characteristics of lung cancer with chronic obstructive pulmonary disease].

Forty-two lung cancer patients with COPD (7.9% of 534 lung cancers), and 84 age- and sex-ratio-matched controls who were randomly selected from lung cancer patients without COPD were examined. Lung cancers with COPD consisted of 25 cases of squamous call carcinoma (59.5%), 11 of adenocarcinoma (26.2%), 2 of small-cell carcinoma (4.8%), and 4 of large-cell carcinoma (9.5%). Squamous cell carcinoma occurred more in patients with COPD than in controls (35.7%) (p less than 0.01). In squamous cell tumors with COPD, 12 cases (48.0%) were centrally located and 13 cases (52.0%) were peripherally located. Squamous cell carcinoma of peripheral origin occurred more in patients with predominant emphysema (76.9%) than controls (36.7%) (p less than 0.05). Our results suggest that the COPD patients with predominant emphysema may be at greater risk for squamous cell tumors of peripheral origin.

Adenocarcinoma↗

[A case of primary pulmonary hypertension with high venous thromboxane B2 concentration].

A 30-year-old male was admitted because of dyspnea, which had started three years before the admission. Chest roentgenogram showed prominence of the proximal pulmonary arteries and diminished vascularity of the peripheral pulmonary arteries. Electrocardiogram showed right axis deviation and right ventricular hypertrophy. Right heart catheterization revealed a markedly elevated pulmonary arterial pressure and pulmonary vascular resistance with normal capillary wedge pressure. Oximetry showed no evidence of intracardiac shunt. Perfusion lung scan revealed nonsegmental, patchy defects in both lungs. Pulmonary arteriography showed no evidence of pulmonary thromboembolism. From the above findings, primary pulmonary hypertension was diagnosed. Nifedipine, ISDN, prazosin, and captopril were administered to evaluate the short term-effect of he vasodilators. Nifedipine was found to be the most effective. The venous thromboxane B2 level was high. After oxygen therapy, venous thromboxane B2 level fell within the normal range following improvement of arterial oxygenation and decrease in venous FDP level. Hemodynamic changes induced by ice-water hand immersion showed marked increase in the mean pulmonary arterial pressure and total pulmonary arterial resistance. These results suggested that chemical mediators such as thromboxane, and pulmonary arterial vasospasm were involved in the pathogenesis.

Adult↗

[A case of pulmonary sarcoidosis which exacerbated bronchial asthma in remission].

A 34-year-old woman had history of bronchial asthma in childhood, was admitted complaining of coughs and wheezes. Chest X-ray examinations showed bilateral hilar lymphadenopathy. A diagnosis of bronchial asthma was made because of her past history, reversible airflow limitation and moderate bronchial hyperreactivity. In addition, findings of chest X-ray films and TBLB specimens were indicative of pulmonary sarcoidosis. When bilateral hilar lymphadenopathy disappeared, her wheezes and bronchial hyperreactivity also improved. In this case, it was suggested that pulmonary sarcoidosis was a factor which worsened bronchial hyperreactivity and bronchial asthma which had been in remission.

Adult↗

Cloning and characterization of cDNA for mitochondrial GTP:AMP phosphotransferase of bovine liver.

Three different types of cDNA clones for mitochondrial GTP:AMP phosphotransferase (AK3) were isolated from a cDNA library of bovine liver poly(A)+ RNA. Nucleotide sequencing revealed that each of these clones consisted of a common 5'-untranslated region, a common AK3-coding sequence and a 3'-untranslated region with different sizes. By Northern blot analysis, three species of AK3 mRNA apparently corresponding to the isolated cDNA clones were detected, which would be a result of varying terminations and polyadenylations of the primary transcript. From comparison of the size of the product synthesized in vitro from the message directed by the isolated cDNA with that of the purified AK3 protein, AK3 appeared to have no cleavable NH2-terminal sequence as found in other mitochondrial proteins. The AK3 cDNA was expressed in Escherichia coli, which resulted in complementation of an adenylate kinase mutation of E. coli. The AK3 product was exported to the periplasmic space through the bacterial inner membrane. The possible involvement of the NH2-terminal sequence of the protein in targeting to the mitochondrial matrix was discussed.

Amino Acid Sequence↗