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Biomedical subjects

Y Hirokawa

Publications and source records attributed to Y Hirokawa.

At least 55 records · Page 3Linked to original sources

Focal nodular hyperplasia in an adolescent with glycogen storage disease type I with mesocaval shunt operation in childhood: a case report and review of the literature.

As patients with glycogen storage disease type I survive longer, cases with hepatic tumor have been increasingly documented. A 16 year old boy with glycogen storage disease type I was evaluated for multiple liver tumors. He was diagnosed on clinical features at 9 months of age and underwent a mesocaval shunt operation at 5 years of age. The biopsy of one of the masses showed focal nodular hyperplasia. This is uncommon in patients with glycogen storage disease type I, compared to those with adenoma or malignant hepatic tumor. The association of a portacaval shunt with focal nodular hyperplasia is significant compared to other tumors. An environment of high estrogen concentration or sex hormone binding globulin accompanied by shunt operation may cause focal nodular hyperplasia to develop in the liver of patients with glycogen storage disease type I.

Adolescent↗

Rush immunotherapy with house dust extract in patients with mild extrinsic asthma.

Rush immunotherapy (RIT) with house dust extract was given to 15 patients with mild extrinsic or mixed asthma. Every patient was strongly positive for IgE on the radioimmunosorbent test and sensitive to house dust extract on the scratch skin test. Nine patients were positive on the bronchial provocation test to house dust extract and 6 could not be examined. All patients did not drop out and got to house dust extract solution 10(-1) within 1 week. The symptom-medication scores decreased significantly after RIT. During RIT 1 patient developed a mild asthmatic attack and 3 patients developed generalized skin reaction. Eight weeks later, the threshold for house dust-provoked bronchoconstriction increased in 9 patients, but did not in 3 patients. The blood eosinophil count and blood histamine level significantly decreased. We conclude that RIT is able to raise antigen concentrations for a short periods and effective but not risky for mild asthma.

Adolescent↗

Tracheal, circulatory, and respiratory responses to femoral nerve stimulation.

Tracheal, circulatory, and respiratory responses to electrical stimulation of the afferent nerve from the hindlimb were analyzed in decerebrate, paralyzed, and mechanically ventilated dogs. Tension of the tracheal smooth muscle (TSM), arterial blood pressure, and phrenic nerve activity (PNA) were measured during stimulation of the proximal end of the transected femoral nerve (FNS) with train pulses (duration; 0.5 ms, frequency; 40 Hz). With low intensity (e.g., 0.62 V) FNS, TSM exhibited relaxation, arterial pressure decreased, and neural respiratory output (NRO) was reduced (3 of 8 dogs) or unchanged (5 of 8 dogs). With increases in stimulus intensity, TSM always exhibited relaxation while arterial pressure and NRO exhibited excitatory responses almost at the same thresholds (approximately 5 V). The TSM relaxation and the excitatory NRO and arterial responses augmented with increases in stimulus intensity up to 16 times of threshold of the excitatory NRO response. TSM response was blocked by intravenous atropine but pressor response and phrenic response were not. The arterial response disappeared after administration of a ganglionic blocker. These findings suggest that TSM, arterial pressure, and PNA may be controlled by one neuronal mechanism during high intensity FNS, but that arterial pressure and PNA may be modified by another mechanism in an inhibitory direction when the stimulus intensity is low. This study suggested the existence of a neural mechanism which controls the airway and cardiorespiratory systems properly to execute exercise. Physiological significance of the responses to low intensity femoral nerve stimulation was uncertain.

Animals↗

Differences in motor control in the bronchus and extrathoracic trachea.

The motor control of the bronchus and extrathoracic trachea was evaluated by continuously measuring bronchial diameter and tracheal muscle tension as well as phrenic nerve activity in decerebrated, paralyzed, artificially ventilated dogs. Spontaneous rhythmic changes in bronchial diameter and tracheal muscle tension occurred in phase with phrenic burst during mechanical ventilation and during apnea induced by disconnecting the ventilator. There was a small but consistent difference in the timing of their rhythmic activities; bronchial constriction started at mid-inspiration, whereas tracheal contraction began just prior to the end of inspiration. Both were active in the post-inspiratory phase. Both hypercapnia and apnea caused an enhanced rhythmic constriction of the bronchus, while evoking a tonic contraction of the trachea. Intermittent electric stimulation of the efferent vagus nerves revealed that repetitive stimulation with a short intermission was necessary to evoke a sustained constriction of the bronchus, and that the bronchus could maintain the sustained constriction only transiently. These results indicate that the motor control of the bronchus and extrathoracic trachea are distinct. The central nervous system may contribute to the difference in timing of the contraction between tracheal and bronchial smooth muscle. However, the difference in response to electric stimulation of the nervus vagus may be attributed to the peripheral neuromuscular system.

Animals↗

Tenascin in breast cancer development--is epithelial tenascin a marker for poor prognosis?

(1) In mouse mammary gland development, immunoreactive tenascin (TN) is expressed in the dense mesenchyme surrounding the epithelial component of 14-day embryos, endbuds at puberty, and tumors. (2) Cells that produce TN are myofibroblastic and are characterized by nuclear invaginations, rough endoplasmic reticulum, and pinocytotic vesicles. These cells are not normally present in the stroma of mammary glands but present in cancer stroma, originating probably from fibroblasts differentiated under the influence of TGF-beta 1 stimulation. (3) Breast cancer cells are capable of synthesing TN under certain conditions. TN-non-producing MCF7 cells can produce TN when co-cultured with embryonic fibroblasts or with their conditioned medium. (4) Nine primary human breast cancers were examined for TN expression by in situ hybridization. TN mRNA was expressed in all nine cases in the stroma and in four cases in carcinoma cells as well. (5) Immunohistochemistry for TN was performed in human breast cancers, and it was found that the five-year survival after surgery was markedly lower in the group whose cancer cells were positive [corrected] for TN. TN expression in cancer cells appears to indicate poor prognosis.

Biomarkers, Tumor↗

Recurrent lower gingival squamous cell carcinoma spreading along the pathway of the inferior alveolar nerve.

Computed tomography images showed recurrent lower gingival squamous cell carcinoma spreading from the mandibular foramen to the middle cranial fossa. This extensive tumor spread followed exactly the same anatomic pathway as the inferior alveolar nerve. Histopathologic examination revealed squamous cell carcinoma. Tumor spread was thought to be caused by perineural invasion. This case demonstrates computed tomography features of perineural tumor spread along the inferior alveolar nerve.

Carcinoma, Squamous Cell↗

Development of potent serotonin-3 (5-HT3) receptor antagonists. I. Structure-activity relationships of 2-alkoxy-4-amino-5-chlorobenzamide derivatives.

A new series of 2-alkoxy-4-amino-5-chlorobenzamide derivatives bearing five- to seven-membered heteroalicyclic rings in the amine moiety was synthesized and evaluated for serotonin-3 (5-HT3) receptor antagonistic activity by assaying the ability to antagonize the von Bezold-Jarisch reflex in rats. The five- to seven-membered heteroalicycles comprise pyrrolidine, morpholine, 1,4-thiazine, piperidine, piperazine, 1,4-oxazepine, 1,4-thiazepine, azepine, and 1,4-diazepine rings. Among them, some benzamide derivatives having a 1,4-diazepine ring showed a potent 5-HT3 receptor antagonistic activity. In particular, 4-amino-5-chloro-N-(1,4-dimethylhexahydro-1H-1,4-diazepin-6- yl)-2- ethoxybenzamide (96) and the 1-benzyl-4-methylhexahydro-1H-1,4-diazepine analogue 103 showed potent 5-HT3 receptor antagonistic activity without 5-HT4 receptor binding affinity.

Animals↗

Development of potent serotonin-3 (5-HT3) receptor antagonists. II. Structrue-activity relationships of N-(1-benzyl-4-methylhexahydro-1H-1,4- diazepin-6-yl)carboxamides.

Our studies on 4-amino-5-chloro-2-ethoxybenzamides led to the discovery that the N-(1,4-dimethylhexahydro-1H-1,4-diazepin-6-yl)benzamide 9 and the 1-benzyl-4-methylhexahydro-1H-1,4-diazepine analogue 10 are potent serotonin-3 (5-HT3) receptor antagonists. Structure-activity relationship (SAR) studies on the influence of the aromatic nucleus of 9 and 10 upon inhibition of the von Bezold-Jarisch reflex in rats are described. Heteroaromatic rings such as pyrrole, thiophene, furan, pyridine, pyridazine, 1,2-benzisoxazole, indole, quinoline, and isoquinoline rings showed weak 5-HT3 receptor antagonistic activity. Within this series, use of the 1H-indazole ring as an aromatic moiety led to a substantial increase of the activity; the 1H-indazolylcarboxamides 54, 57, 97, and 102 showed potent 5-HT3 receptor antagonistic activity. The optimal compound identified via extensive SAR studies was N-(1-benzyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-1H-indaz ole-3- carboxamide (54), whose effect was superior to that of the corresponding benzamide 10 and essentially equipotent to those of ondanbsetron (1) and granisetron (4).

Animals↗

[Neural control of tracheal smooth muscle during cough].

Contraction of tracheal smooth muscle during mechanically induced coughing was studied in dogs. Recordings of smooth muscle tension were obtained from the cervical trachea, which is not influenced by intrathoracic pressure. We observed that during breathing at rest, tracheal smooth muscle contracts and relaxes in synchrony with phrenic nerve activity. When cough occurs, the tracheal smooth muscle contracts continuously and tonically with no rhythmic correlation to phrenic nerve activity. Sometimes the contraction starts before the phrenic nerve activity increases. A neuromuscular blocking agent caused a significant decrease in phrenic nerve activity in response to mechanical stimulation. The correlation between phrenic nerve activity and tracheal smooth muscle tension during normal breathing was also observed after afferent inputs from pulmonary mechanoreceptors were interrupted. During coughing, however, this correlation was lost. From these results we conclude that the neural control of tracheal smooth muscle is at least partially independent of phrenic nerve activity during coughing. Because coughing was attenuated by neuromuscular blocking agents, we speculate that there is a positive feedback mechanism from receptors in the chest wall or airway, which increases the magnitude of coughing.

Animals↗

[Efficacy and assessment of patient education as related to morbidity from asthma].

Asthmatic patients are sometimes ignorant of their treatment and of the pathophysiology of their disease. In such patients, anxiety about the disease may worsen their condition. We studied the effects of an educational program for bronchial asthma. In 45 patients, the Severity of Asthma Scores before and after the program were measured. Sixty percent of the patients were assessed as "improved". On self-administered questionnaires concerned with asthma, most of the patients indicated that the program significantly improved their condition, reduced apprehension about the disease, and increased their trust in the hospital. In 24 patients, three psychological tests were done. Results of the comprehensive asthma inventory indicated that the program was useful for dependent and self-disciplined patients, but was not useful for resigned and depressed patients. The Y-G test showed that most of the patients who were helped by the program were introverted. Results of the Edwards Personal Preference Schedule revealed a difference in desire between the group that benefitted from the program and the group that did not. These results suggest that each group had a certain inclination toward psychogenic symptoms. Therefore, psychological tests are useful for predicting the effects of education. In conclusion, educational programs for patients with bronchial asthma may affect morbidity from asthma. Possible mechanisms include relief of anxiety about the disease and improvement in the patient's compliance with prescribed therapy.

Anxiety↗

[Clinical characteristics and outcome of 508 patients with hyperventilation syndrome].

The characteristics of hyperventilation syndrome (HVS) were studied in 508 patients who visited our hospital over 11 years. Information regarding symptoms and laboratory data was collected from the clinical records, and outcome was surveyed with a questionnaire mailed to all patients. Patients with acute HVS ranged in age from 5-85 years, and acute HVS was particularly prevalent among women in their late teens. Triggers of HVS included anxiety, nausea & vomiting, and fever due to the common cold. The primary symptoms were dyspnea and numbness, but these differed from the symptoms that appeared during a provoked attack, Half of the patients had no underlying disorder, but the others were suffering from neurosis, cardiovascular disorders, or other diseases. These characteristics of acute HVS did not differ from those seen in patients in whom the diagnosis of HVS was confirmed with arterial blood gas analysis. Half of the patients recovered without treatment, and the others underwent paper-bag rebreathing or intravenous infusion of sedatives. The prevalence of chronic HVS was 2% and almost all those patients were middle-aged women. In contrast, the questionnaire revealed that half of the patients had repeated HVS attacks. In 10% of the patients, these attacks persisted for more than 3 years. Many of these patients reported that they sighed frequently and felt air hunger while in remission. These findings were compatible with the criteria for chronic HVS. Therefore, it may be possible to diagnose HVS from symptoms alone, without hyperventilation provocation tests. In conclusion, these data underscore the importance of clinical symptoms in the diagnosis of HVS.

Adolescent↗

Mediation of the physiological response of platelets by interactions of spectrin and protein 4.1 with the cytoskeleton.

Spectrin and protein 4.1 became associated with the Triton-insoluble cytoskeletons during platelet activation. Inhibition of platelet activation by a PGI2 analogue resulted in release of the proteins from the cytoskeletons. Changes in subcellular distributions of the proteins preceded changes in the state of platelet aggregation. These results suggest that interactions of spectrin and protein 4.1 with the cytoskeletons are involved in mediating the physiological response of the platelet.

Actins↗

Dose-reducing effect of Lipowitz metal-embedded spacers in interstitial brachytherapy for carcinoma of the mobile tongue.

Dose-reducing effects of spacers with and without a Lipowitz metal plate for the purpose of decreasing osteoradionecrosis after interstitial brachytherapy for tongue cancers were examined experimentally and clinically. The thicker the sample or spacer and the thicker the metal plate, the greater was the dose reduction achieved. A more marked dose reduction was achieved with iridium than with radium because of lower gamma ray energy of iridium. Iridium has been used widely as a radioactive source for interstitial brachytherapy. It was concluded therefore that a metal plate should be used as a shield into the spacer in interstitial brachytherapy both to reduce the radiation dose to surrounding normal tissues and to help prevent osteoradionecrosis.

Alloys↗

Tenascin expression and postnatal development of the human prostate.

We investigated the distribution of tenascin during postnatal development of the human prostate. Monoclonal antibody specific to human tenascin was applied to paraffin sections by the avidin-biotin-complex method to examine its localization. Infantile prostates showed two distinct zones. The inner zone had sparse acini with fibromuscular bundles. The peripheral zone had similar acini and lighter stroma as compared with inner zone. Tenascin was found diffusely but weakly. The periglandular area occasionally showed immunoreactivity. The prostates from 9- to 13-year-old subjects had a morphology similar to that of the infantile gland. The difference was increased density of the acini. Immunoreactivity was low. In the prostates from 14- to 21-year-old subjects, the acini distribution was more crowded, and the epithelial lining had become taller in both zones. Tenascin distributed preferentially in the peripheral zone during this period. Simultaneously, the percent of glandular area in the peripheral zone rose abruptly. The dynamics of tenascin expression are closely associated with the development and maturation of the gland. The distribution of tenascin during the post-puberal period may suggest its participation in the preferential of prostatic carcinoma in the peripheral zone.

Adolescent↗

[Apoptosis in radiosensitive malignant tumors].

This study reported the radiation induced apoptosis in 6 cases with malignancies that were observed rapid tumor regression with radiotherapy up to 10 Gy. Microscopic examinations of 6 cases revealed the tumor cell number reduction and the appearance of apoptotic cells in the irradiated cases. It is suggested that the radiation-induced apoptosis plays an important role in rapid tumor regression by radiotherapy and occurs not only in lymphoma which has been recently reported in vitro but also in carcinoma.

Apoptosis↗

Serotonin innervation patterns differ among the various medullary motoneuronal groups involved in upper airway control.

The purpose of this study was to test our hypothesis that the serotoninergic system plays a significant role in airway obstruction during sleep, by focusing on patterns of serotoninergic innervation of the medullary motoneurons involved in upper airway control. We used the combined techniques of retrograde labelling of motoneurons with unconjugated cholera toxin B and immunohistochemistry with antiserum against serotonin (5-HT). The retrograde tracers were injected into posterior cricoarytenoid (PCA), cricothyroid (CT), and genioglossal (GG) muscles of the cat. Motoneurons retrogradely labelled from PCA were identified ipsilateral to the injection site in the caudal part of nucleus ambiguus (NA). Serotonin immunoreactive terminals surrounded their somata and proximal dendrites, suggesting a strong influence of serotonin on the PCA-labelled motoneurons. Motoneurons retrogradely labelled from CT were located ipsilaterally in two distinct groups in the rostral NA and in the retrofacial nucleus (RFN). Selective peripheral nerve section revealed that the CT-labelled motoneurons in the NA had axons in the recurrent laryngeal nerve, whereas the other CT-labelled motoneurons in the RFN were innervated through the superior laryngeal nerve. In the RFN, the pattern of 5-HT innervation in relation to the CT-labelled motoneurons was analogous to that observed with the PCA-labelled motoneurons. In the NA, however, 5-HT terminals made few contacts with the CT-labelled motoneurons, although a dense network of 5-HT terminals was present in the surrounding region. In the GG-labelled motoneuron region of the hypoglossal nucleus, 5-HT terminals were apposed to distal dendrites, not to the soma, indicating less effect of serotonin on GG than on PCA activity. The present results demonstrated that the patterns of 5-HT innervation vary according to the type of motoneurons and their projections to the upper airway.

Animals↗

Experimental and clinical studies on dose reduction effects of spacers in interstitial brachytherapy for carcinoma of the mobile tongue.

The difference of radiation dose reduction effect with spacers of different materials, a heat-curing denture base resin and a silicon impression material, was examined experimentally and clinically. Radium needles and iridium hairpins were used as radioactive sources. In both studies, it was revealed that a dose reduction effect of silicon impression material was greater than that of denture base resin. Silicon impression material was thought to be a better material for spacers because of its larger radiation dose reduction effect and the time saving to produce the spacer.

Brachytherapy↗

Centrally driven slow oscillating potential of extrathoracic trachea.

Spontaneous electrical activity of extrathoracic trachea was recorded along with force developed by tracheal smooth muscle and phrenic nerve activity in decerebrated, paralyzed, and artificially ventilated dogs with pneumothorax. The tracheal electrical activity exhibited slow oscillating potentials that were coupled with spontaneous phasic contraction of trachea. Both rhythmic changes were synchronous with central respiratory rhythm represented by phrenic burst, independent of the respirator's rhythm. The dominant component of the slow oscillating potentials consisted of sinusoidal waves with large amplitude that occurred shortly after cessation of phrenic burst, i.e., in the postinspiratory phase. The concomitant small change in the slow oscillating potentials began in the late inspiratory phase just before the initiation of the tracheal contraction. This phase relationship was preserved after removal of intrathoracic vagal afferents from lungs. Such slow oscillating potentials were also observed during lung collapse produced by disconnecting the tube attached to the respirator. Transection of recurrent laryngeal nerves abolished the slow oscillating potentials. These results indicate that the slow oscillating potentials of the extrathoracic trachea are generated by a physiological process associated with the central respiratory rhythm. The dominant component of the slow oscillating potentials occurs in the postinspiratory phase.

Anesthesia↗