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Biomedical subjects

K Hiraga

Publications and source records attributed to K Hiraga.

At least 91 records · Page 5Linked to original sources
PubMed1991

The glycine cleavage system: structure of a cDNA encoding human H-protein, and partial characterization of its gene in patients with hyperglycinemias.

We have isolated a 1,192-base-long cDNA which encodes the entire structure of a precursor form of human H-protein. The tentatively calculated number of copies for this cDNA appeared to be about four times as many as that of the antithrombin III gene specified by a single locus in the human haploid genome. Southern analysis using H-protein cDNA probe demonstrates a deletion of the 5.0-kb SacI fragment in the genome of a patient with an atypical nonketotic hyperglycinemia in whom there was an inactive H-protein. This SacI fragment was also deleted from the genome of one of seven patients with nonketotic hyperglycinemia resulting from the lesion of glycine decarboxylase. The remaining six patients had common aberrations identified with the 5.2-kb EcoRI and 5.5-kb SacI fragments. Although implication of these defective fragments in pathogenesis is unclear at present, it is suggested that rearrangements occur in multiple genomic loci of patients with nonketotic hyperglycinemia and that this H-protein cDNA can be used for carrier screening.

Amino Acid Oxidoreductases↗
PubMed1991

The incidence of cancer pain and improvement of pain management in Japan.

A nation-wide survey (1987) of cancer pain and analgesic methods showed that the incidence of pain in the terminal stage was in the range of 68 to 72% without any significant difference between hospital groups. Irrespective of the stage of illness, a certain analgesic effect was obtainable with oral/parenteral use of opioids. As a result of a year-to-year comparison of pain in cancer clinics, it was found that the rate of complete pain relief has increased for all stages of illness, especially in the terminal stage. Here the rate of complete pain relief steadily increased from 37.8% in 1986 to 42.7% in 1987 and 48.6% in 1988. Propagation of WHO-advocated cancer pain therapeutics has led to an improvement of the rate of pain relief in the terminal stage. Marketing of MS Contin tablets resulted in a dramatic increase in the consumption of morphine, but there was no increase in the rate of pain relief due to poor measures to counter adverse reactions, and to administration of morphine in insufficient doses. The consumption of morphine for medical use increased year by year, but a greater number of doctors experienced in the use of opioids would further improve the management of pain. To realize that, it would be necessary to incorporate terminal care into medical education programmes as soon as possible. Further efforts will be required for extensive research and propagation of analgesic methods in various fields including education in medicine, science of nursing and postgraduate education.

Adult↗
PubMed1991

Relationship between plasma concentration of morphine and analgesic effectiveness.

Morphine is a key drug for cancer pain management. In this study, we analyzed plasma morphine concentration in cancer patients who received continuous morphine drip and/or oral administrations of morphine: (1) The plasma concentration of morphine varied widely in patients whose pain was satisfactorily controlled at a constant dosage of morphine. The absolute value of the plasma concentration of morphine necessary for effective pain control could not be estimated; (2) When MS Contin was given at the doses 20 mg, 30 mg, 40 mg, the plasma concentration of morphine increased with increasing dose. Thus, when the dose was increased according to the severity of pain, the plasma concentration of morphine increased and in turn an analgesic effect was obtained; (3) In those patients who had difficulty in taking oral preparations and/or blocked intestines, plasma concentration of morphine following oral administration was relatively low causing an unsatisfactory analgesic effect. However, by changing from oral administration to continuous drip infusion, the plasma concentration of morphine became higher and pain relief was obtained; (4) Continuous drip infusion of morphine progressively increased plasma concentration of morphine in parallel with the increase in the dose of morphine if the patients had no pleural effusion, ascites, and/or oedema. In contrast, plasma morphine concentration in patients with pleural effusion, ascites, and/or oedema was about half of that observed in patients who have normal distribution area. The rapid development of pleural effusion and ascites lowers the blood level of morphine; (5) To use the plasma concentration of morphine as an index for the analgesic effect, it is essential to develop a method to measure the plasma concentration of morphine rapidly.

Aged↗
PubMed1991

Non-ketotic hyperglycinemia: an aim of the second generation of studies on pathogenesis.

Non-ketotic hyperglycinemia is caused by a molecular lesion involved in the glycine cleavage system and shows striking features representing the impaired central nervous system. For the study on molecular genetics of non-ketotic hyperglycinemia, we have isolated several cDNA clones, each encoding human glycine decarboxylase of H-protein, two of the four component enzymes of the glycine cleavage system. Although one of eight patients with this disease resulting from a lesion of glycine decarboxylase had the glycine decarboxylase gene deleted at a 5' region, they showed no common aberration detectable by glycine decarboxylase cDNA. Using the H-protein cDNA, we have demonstrated the rearranged structures, identified by one of the undetectable 5.0 and 5.5 kb SacI fragments, in the genomes of patients in whom there was an impaired expression of H-protein or glycine decarboxylase. The aberration of the 5.5 kb SacI fragment was associated with a defect of the 5.2 kb EcoRI fragment. Multiple genomic lesions are suggested for non-ketotic hyperglycinemia, and their implications in pathogenesis are discussed.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

One of the two genomic copies of the glycine decarboxylase cDNA has been deleted at a 5' region in a patient with nonketotic hyperglycinemia.

One of eight patients with nonketotic hyperglycinemia resulted by the lesion in glycine decarboxylase showed the deletion of 0.6-kb SacI and 1.5-kb PstI fragments identified by the cDNA for this protein. A genomic clone, lambda HGDG10, encodes a 5' region of this cDNA in an organized structure and can produce these two fragments. The other clone, lambda HGDG8, carries a processed gene. Southern analysis using a limited segment of this cDNA demonstrated that the 1.7-kb and 1.5-kb PstI fragments predicted from its recognition sites in both genomic clones occur actually in the human genome, indicating that at least two copies of glycine decarboxylase cDNA exist in the haploid genome, and the patient has the glycine decarboxylase gene deleted at a 5' region.

Amino Acid Oxidoreductases↗
PubMed1990

Changes in breathing patterns after lung operations.

To assess the effects of thoracic surgery on breathing patterns without conscious intervention, we analyzed and compared the breathing patterns observed immediately before and after surgical procedure while anesthesia was maintained with enflurane and nitrous oxide at a constant level in 15 patients undergoing thoracic surgery. Our results showed that immediately after the surgical procedure, respiratory frequency (f) was significantly higher and tidal volume (V(T)) was significantly smaller than those observed immediately before the surgical procedure. The increased f during the period immediately after the surgical procedure was due to shortening of both inspiratory time (T(I)) and expiratory time (T(E)) without changing the ratio of T(I) to the total breath time (T(tot)). Despite the significant decrease in V(T) observed immediately after the surgical procedure, the value of negative pressure during the occluded inspiration (P(max)) was significantly higher than that observed immediately before the surgical procedure. These results indicate that a rapid, shallow type of breathing pattern can occur after thoracic surgery without conscious intervention.

Journal Article↗
PubMed1990

Effects of i.v. lignocaine on airway reflexes elicited by irritation of the tracheal mucosa in humans anaesthetized with enflurane.

We have investigated the effects of bolus administration of lignocaine 1.5 mg kg-1 i.v. on respiratory responses to airway irritation induced by instillation of distilled water into the trachea in 10 patients anaesthetized with enflurane (1.5% end-tidal). Before administration of lignocaine, airway irritation elicited not only the cough reflex, but also other respiratory reflexes such as expiration, apnoea and spasmodic panting. Immediately after administration of i.v. lignocaine, when plasma concentrations of lignocaine exceeded 4.7 micrograms ml-1, tracheal irritation elicited only brief apnoea. Other reflex responses were suppressed completely; they recovered gradually with progressive decrease in plasma concentration of lignocaine. The apnoeic reflex was not eliminated at plasma lignocaine concentrations greater than 7.0 micrograms ml-1, whereas the expiration reflex, cough reflex and spasmodic panting were eliminated effectively by plasma concentrations of lignocaine greater than 3.5, 2.8 and 2.2 micrograms ml-1, respectively.

Adult↗
PubMed1990

Laryngeal and respiratory responses to tracheal irritation at different depths of enflurane anesthesia in humans.

The effect of three different depths of enflurane anesthesia (1.0, 1.4, and 1.8 MAC) upon laryngeal and respiratory responses to tracheal instillation of distilled water in nine female patients in whom a double-cuffed endotracheal tube had been inserted was investigated. The laryngeal responses were monitored by measuring the pressure in the saline-filled cuff positioned within the larynx, and the respiratory responses were monitored by measuring ventilatory flow and tracheal airway pressure. Increases in laryngeal cuff pressure in response to tracheal irritation were 19.7 +/- 4.5 cmH2O (mean +/- SD) at 1.0 MAC, 13.9 +/- 3.6 cmH2O at 1.4 MAC, and 7.6 +/- 1.8 cmH2O at 1.8 MAC, respectively (P less than 0.01 for anesthetic dose). At 1.0 MAC of enflurane anesthesia, tracheal instillation of saline caused immediate laryngeal constriction and all components of the tracheal response, such as apnea, expiration reflex, cough reflex, and spasmodic panting. At 1.4 and 1.8 MAC, the same stimulation caused only apnea and constriction of the larynx in the majority of patients. These results indicate that changes in depth of anesthesia can modify the laryngeal and respiratory responses to tracheal irritation. The close association of laryngeal and respiratory responses may be an integral part of the defensive reflex synergism.

Adult↗
PubMed1990

Effects of tracheal irritation and hypercapnia on tracheal smooth muscle in humans.

Both hypercapnia and tracheal irritation are known to constrict the airways in animals. To see whether similar responses occur in humans, we investigated tracheal smooth muscle (TSM) responses to hypercapnia and tracheal irritation with water in 14 paralyzed and anesthetized humans. TSM tone was monitored by measuring the pressure in the saline-filled cuff of the endotracheal tube. Although, tracheal irritation caused TSM constriction in 10 of 14 patients, 4 patients showed no TSM response. Administration of intravenous atropine attenuated the TSM constriction response. Hypercapnia did not cause any change in TSM tone in any of the 14 patients. These results indicate that in paralyzed and anesthetized humans, there exist interindividual differences in the TSM responses to tracheal irritation and that hypercapnia cannot be an effective stimulus for the TSM constriction.

Adult↗
PubMed1990

[Influence of hypercapnia on circulatory response to endotracheal intubation].

Effects of CO2 on circulatory responses to laryngoscopy and endotracheal intubation were investigated in 16 patients under constant depth of enflurane anesthesia (1.2MAC) at different levels of CO2 (normocapnia, PETCO2: 40mmHg or hypercapnia, PETCO2: 60mmHg). Patients were randomly divided into two groups; normocapnia group (n = 8) and hypercapnia group (n = 8). Although there was no significant difference in blood pressure response to laryngoscopy and endotracheal intubation between normocapnic and hypercapnic groups, heart rate response was significantly attenuated in hypercapnic group and the latent period between the start of laryngoscopy and the onset of increase in heart rate was significantly longer in hypercapnic group. Our results suggest that hypercapnia exerts inhibitory influence on heart rate responses to laryngoscopy and endotracheal intubation.

Adult↗
PubMed1989

The effects of thiamylal sodium on the tonic vibration reflex in man.

The effects of barbiturate on the tonic vibration reflex (TVR) in man were studied. Motor unit spikes elicited during the TVR were recorded before and after an intravenous injection of thiamylal sodium. Thiamylal sodium at a dose between 1.5 and 5.8 mg/kg depressed the motor unit response to muscle vibration. Analysis using a cross-correlation between vibratory stimuli and motor unit spikes confirmed the previously reported existence of two types of motor unit response, i.e. spikes that are locked and those that are not locked to the vibratory stimuli. In addition, the latter type was susceptible to the depressant effects of thiamylal than the former type. Some possible explanations for the difference in susceptibility of the two types of motor unit to barbiturate are discussed, placing special emphasis on the probable participation of polysynaptic connections from group Ia afferents to motoneurons in the generation of the human TVR.

Adult↗
PubMed1989

Identification of a wheat germ agglutinin-sensitive ATPase in yeast nuclei.

We have found that wheat germ agglutinin (WGA), a lectin that specifically binds to N-acetylglucosamine residues inhibits the in vitro transport of plasmid DNA, pJDB219, into yeast nuclei. Histochemical staining of the isolated nuclei with biotinylated WGA and streptavidin-biotinylated peroxidase complex revealed the presence of WGA-binding materials around the nuclear pore under an electron microscope. Using WGA-agarose column chromatography of yeast nuclear extracts, a novel Mg2+-dependent ATPase was isolated. Its activity was highly sensitive to WGA and stimulated by Nonidet P-40 or phosphatidylserine. We suggest that the WGA-sensitive ATPase plays a role in yeast nuclear transport of DNA.

Adenosine Triphosphatases↗
PubMed1989

High-resolution electron microscopy study on crystal structures of high-Tc superconductors.

Recent studies of high-resolution electron microscopy on the high-Tc superconductors of Y-Ba-Cu-O and Bi-Ca-Sr-Cu-O are presented. The observed images of crystals thinner than 3 nm, taken under conditions that approached the Scherzer defocus condition, directly show the arrangements of cations and oxygen-vacant positions. The results reveal structural characteristics of the atomic scale; this offers important insights into the origin of the high-Tc superconductivity. The usefulness of high-resolution electron microscopy for studying complicated crystal structures is demonstrated for the high-Tc oxides.

Bismuth↗
PubMed1989

Inhibitory effects of CO2 on airway defensive reflexes in enflurane-anesthetized humans.

We investigated responses of respiration, blood pressure, and heart rate to tracheal mucosa irritation induced by injection of distilled water at three different levels of CO2 ventilatory drive in 11 spontaneously breathing female patients under a constant depth of enflurane anesthesia [1.1 minimum alveolar concentration (MAC)]. The airway irritation at the resting level of spontaneous breathing caused a variety of respiratory responses such as coughing, expiration reflex, apnea, and spasmodic panting, with considerable increases in blood pressure and heart rate. Although the latency of respiratory responses after water injection was much shorter than those of blood pressure and heart rate responses, blood pressure and heart rate responses, once elicited, were prolonged much longer than was the respiratory response. An increase in CO2 ventilatory drive decreased the degree and duration of respiratory, blood pressure, and heart rate responses to the airway irritation, whereas a decrease in CO2 ventilatory drive had the opposite effect on these responses. Our results indicate that changes in CO2 ventilatory drive can modify reflex responses of respiration, blood pressure, and heart rate to airway irritation.

Adult↗
PubMed1989

Influence of CPAP on reflex responses to tracheal irritation in anesthetized humans.

We investigated the effects of lung inflation during continuous positive airway pressure breathing (CPAP) on airway defensive reflexes in 10 enflurane-anesthetized spontaneously breathing humans. The airway defensive reflexes were induced by instillation into the trachea of 0.5 ml of distilled water at two different levels of end-expiratory pressure (0 and 10 cmH2O CPAP). The tracheal irritation at an end-expiratory pressure of 0 cmH2O caused a variety of reflex responses including apnea, spasmodic panting, expiration reflex, cough reflex, an increase in heart rate, and an increase in blood pressure. Lung inflation during CPAP of 10 cmH2O did not exert any influence on these reflex responses in terms of the types, latencies, and durations of reflex responses although the intensity of the expiration reflex and cough reflex was augmented by lung inflation. Our results suggest that the pulmonary stretch receptors do not play an important role in the mechanisms of airway defensive reflexes in humans.

Adult↗