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Biomedical subjects

K Hisamatsu

Publications and source records attributed to K Hisamatsu.

At least 19 recordsLinked to original sources

Update results of FEC followed by docetaxel neoadjuvant trials for primary breast cancer.

This study has been initiated to evaluate the safety, clinical and pathologic response as well as the relation of response (pCR or non-pCR) and survival (overall and relapse-free) of fluorouracil, epirubicin and cyclophosphamide (FEC) followed by docetaxel (DOC) as preoperative chemotherapy in patients with operable breast cancer. Japanese patients with primary breast cancer, Tlc-3N0M0 or T1-3NIM0, age 20-60, PS 0-1 were included in this study. Preoperative chemotherapy consisted of 4 cycles of FEC (500 mg/m(2), 100 mg/m(2), 500 mg/m(2)) every 3 weeks followed by 4 cycles of DOC (75 mg/m(2)) every 3 weeks. Since June 2002, 200 patients were enrolled in this study, and the time of this interim analysis, 80 patients were evaluable for safety and clinical efficacy. The overall clinical response rate was 71.4% (14% CR, 44% PR, 42% SD/PD), and the only G3,4 toxicities, neutropenia and febrile neutropenia were observed in 54% and 14% of patients, respectively. Eighty nine patients were evaluable for pathologic response by central review. Pathologic response was evaluated among invasive tumors on multiple cross-section specimens based on a modified version of the Japanese grading system for Japanese Breast Cancer Society. The pathologic response rate was 17%. In this ongoing trial, FEC followed by DOC was active and well tolerated.

Antineoplastic Agents, Phytogenic↗

Relatively benign clinical course in asymptomatic patients with brugada-type electrocardiogram without family history of sudden death.

INTRODUCTION: The incidence of sudden death or ventricular fibrillation (VF) in asymptomatic Brugada syndrome patients with a family history of sudden death is reported to be very high. However, there are few reports on the prognosis of asymptomatic Brugada syndrome patients without a family history of sudden death. METHODS AND RESULTS: Eleven patients (all male; mean age 40.5 +/- 9.6 years, range 26 to 56) with asymptomatic Brugada-type ECG who had no family history of sudden death were evaluated. The degrees of ST segment elevation and conduction delay on signal-averaged ECG (SAECG) before and after pilsicainide were evaluated in all 11 patients. VF inducibility by ventricular electrical stimulation also was evaluated in 8 of 11 patients. Patients were followed for a period of 9 to 84 months (mean 42.5 +/- 21.6). The J point level was increased (V1: 0.19 +/- 0.09 mV to 0.36 +/- 0.23 mV; V2: 0.31 +/- 0.12 mV to 0.67 +/- 0.35 mV) by pilsicainide. Conduction delay was increased (total QRS: 112.2 +/- 6.3 msec to 131.7 +/- 6.3 msec; under 40 microV: 42.0 +/- 8.5 msec to 52.7 +/- 12.7 msec; last 40 msec: 17.4 +/- 5.9 microV to 10.4 +/- 6.1 microV) on SAECG by pilsicainide. VF was induced in only 1 of 8 patients. None of the patients had syncope or sudden death during a mean follow-up of 42.5 +/- 21.6 months. CONCLUSION: This study suggests that asymptomatic patients with Brugada-type ECG who have no family history of sudden death have a relatively benign clinical course.

Adult↗

Functions and ATP-binding responses of the twelve histidine residues in the TF1-ATPase beta subunit.

The C2 proton signals of all (twelve) histidine residues of the TF1 beta subunit in the 1H-NMR spectrum have been identified and assigned by means of pH change experiments and site-directed substitution of histidines by glutamines. pH and ligand titration experiments were carried out for these signals. Furthermore, the ATPase activity of the reconstituted alpha3beta3gamma complex was examined for the twelve mutant beta subunits. Two of three conserved histidines, namely, His-119 and 324, were found to be important for expression of the ATPase activity. The former fixes the N-terminal domain to the central domain. His-324 is involved in the formation of the interface essential for the alpha3beta3gamma complex assembly. The other conserved residue, His-363, showed a very low pK(a), suggesting that it is involved in the tertiary structure formation. On the binding of a nucleotide, only the signals of His-173, 179, 200, and 324 shifted. These histidines are located in the hinge region, and its proximity, of the beta subunit. This observation provided further support for the conformational change of the beta monomer from the open to the closed form on the binding of a nucleotide proposed by us [Yagi et al. (1999) Biophys. J. 77, 2175-2183]. This conformational change should be one of the essential driving forces in the rotation of the alpha3beta3gamma complex.

Adenosine Triphosphate↗

Pranlukast protects leukotriene C4- and D4-induced epithelial cell impairment of the nasal mucosa in vitro.

To investigate the effect of pranlukast on leukotriene- induced airway mucosal epithelial dysfunction, samples of human nasal mucosa obtained during surgery for facial trauma were exposed to leukotriene C4 and/or D4 and observed on a TV screen magnified x 2,500. Leukotriene C4- and D4-induced ciliary inhibition and delayed mucosal surface alterations appeared several hours later. Pranlukast prevented both the mucosal epithelial cell dysfunction and the delayed epithelial cell alteration.

Adult↗

Peripheral arterial coil embolization for hepatic arteriovenous malformation in Osler-Weber-Rendu disease; useful for controlling high output heart failure, but harmful to the liver.

A 55-year-old Japanese housewife, who had Osler-Weber-Rendu disease, was admitted to our hospital because of frequent epistaxis and worsening exertional dyspnea. The computed tomography and hepatic arteriography revealed large hepatic arteriovenous malformation, which was considered to be the leading cause of her high output heart failure. Two series of hepatic arterial coil embolization procedures were performed to reduce hepatic shunt flow. They temporarily improved her cardiac condition, but gradually induced progressive hepatic failure due to intrahepatic cholangitis. Hepatic dysfunction restricted her quality of life and lead to a fatal clinical course one year after the second coil embolization.

Arteriovenous Malformations↗

The relationship between psychosomatic factors and orthostatic dysregulation in young men.

We carried out a questionnaire survey regarding symptoms of orthostatic dysregulation and administered the Japanese Edition of the Cornell Medical Index-Health Questionnaire (JCMI) and the Yatabe-Guilford Personality Test (Y-G test) to 151 male medical students (mean age, 24.6 yr). Orthostatic dysregulation was identified in 19 (12.5%) of the subjects based on the questionnaire results. The percentage classed as types III (possible neurotic) and IV (probable neurotic) according to the health questionnaire was 47.3% in the 19 with orthostatic dysregulation and 8.9% in the controls (n = 78). The percentage classed as types B and E, suggestive of emotional or psychological disturbance according to the personality test, was 42.1% in those with orthostatic dysregulation and 8.9% in the controls. These differences were significant (P < 0.01). These results suggest that psychosomatic factors influence the occurrence of orthostatic dysregulation in young men.

Abdominal Pain↗

Interaction between oral alpha-streptococci and group A streptococci in patients with tonsillitis.

The incidence of oral alpha-streptococci with inhibitory activity against group A streptococci, as a defense mechanism against bacterial infection in the oral cavity, was investigated in 141 patients with streptococcal tonsillitis. The study population included both children (n = 79) and adults (n = 62). Infection by group A streptococci appeared to be more common in children than in adults, as the detection rates of inhibitory alpha-streptococci in healthy children (29.7%), as well as pediatric patients with tonsillitis (14.9%), were lower than those in adults (63.0%; p < .01). It is possible to consider oral alpha-streptococci with inhibitory activity to be among the indications for tonsillectomy in patients with streptococcal tonsillitis, since the detection rate of inhibitory alpha-streptococci in surgical cases (10.9%) was significantly lower than that in nonsurgical cases (31.1%; p < .01). The high detection rate of these strains during the postoperative state supported the observation that the incidence of group A streptococcal infection was decreased postoperatively. Accordingly, it is useful to investigate bacterial interference between oral alpha-streptococci and group A streptococci in patients scheduled for tonsillectomy.

Adolescent↗

[A case of a premenopausal woman with advanced breast cancer treated with aromatization inhibition in combination with luteinizing hormone-releasing hormone agonist].

A 44-year-old premenopausal woman having local recurrence and pleural and bone metastases of breast cancer was treated with aromatization inhibition in combination with Luteinizing Hormone-releasing Hormone (LH-RH) agonist. The dominant site of metastasis was a painful local lesion invading the chest wall. A partial response by reducing the size of the local lesion was attained 3 months after initiation of treatment. This result suggested that treatment using aromatization inhibition in combination with LH-RH agonist would be effective in premenopausal breast cancer. To confirm the effectiveness of this treatment, comparative study between aromatization inhibition in combination with LH-RH agonist aromatization inhibition alone and anti-estrogen in combination with LH-RH agonist are needed.

Adult↗

The nasopharyngeal bacterial flora in children with otitis media with effusion.

A study was undertaken to evaluate the incidence of nasopharyngeal alpha-streptococci with inhibitory activity against pathogens, as a defense mechanism of the normal bacterial flora against infection. Cultures were taken from the nasopharynges of 43 children with otitis media with effusion (OME). The detection rates of alpha-streptococci with inhibitory activity against Haemophilus influenzae, Streptococcus pneumoniae, Staphylococus aureus and group A streptococci were significantly lower in the nasopharynx than those isolated from the tonsils of the same patients. Moreover, the detection rates of alpha-streptococci with inhibitory activity against all of these pathogens derived from the nasopharynx were lower than those in healthy children, streptococcal strains with activity against H. influenzae and Strep, pneumoniae were also lower than that in patients with tonsillitis. These findings suggest that low nasopharyngeal levels of alpha-streptococci with inhibitory activity against respiratory pathogens may render children susceptible to OME. Further studies are needed to investigate the relationships between the prevalence of pathogens in the nasopharynx and the inhibitory activities of alpha-streptococci against them in order to devise and select optimal treatment for patients with OME.

Antibiosis↗

The relationship between orthostatic dysregulation and the orthostatic test in dizzy patients.

The orthostatic test was administered to 134 dizzy patients (37 males and 97 females) who were identified as having orthostatic dysregulation from December 1990 through November 1994. The mean age of the male and female patients was 42.5 and 44.6 years, respectively, and the peak age decade was the 50s. Among the questionnaire items for orthostatic dysregulation, orthostatic dizziness was the most frequent major symptom and occurred in 116 of the patients (86.6%). Fatigue was the most frequent minor symptom and was found in 97 (72.4%). The incidence of positive orthostatic test results in the patients with orthostatic dysregulation (50.7%) was significantly higher (P < 0.01) than that in the control subjects (27.8%). There was also a significant difference (P < 0.01 or P < 0.05) between systolic pressure decrease during the orthostatic test procedure in the patients with orthostatic dysregulation and that in the control subjects. These results suggest that autonomic imbalance as reflected by the orthostatic dysregulation questionnaire and orthostatic test results is closely related to the occurrence of dizziness or vertigo.

Adolescent↗

Effect of leukotriene C4 exposure on ciliated cells of the nasal mucosa.

To clarify the effects of leukotriene C4 (LTC4) on human ciliated epithelium, ciliary activity of the ethmoid sinus mucosa was measured photoelectrically in tissue culture. At concentrations ranging from 10(-6)M to 10(-9)M, LTC4 showed minimal effects on the ciliated epithelium during the initial 30 minutes of exposure; thereafter, ciliary inhibition was observed in a concentration- and time-dependent manner. Irrigation of the mucosa with culture medium 15 minutes after exposure prevented the LTC4-induced ciliary inhibition. However, irrigation 60 minutes after exposure failed to inhibit 10(-8)M LTC4-induced ciliary dysfunction and mucosal damage. The LTC4-induced ciliary inhibition was blocked in the presence of FPL-55712 and/or Ly-171883, both leukotriene receptor antagonists. L-serine and sodium tetraborate complex (SBC), a gamma-glutamyl transpeptidase (gamma-GTP) inhibitor, also inhibited the LTC4-induced ciliary inhibition. These findings indicate that LTC4 is converted to LTD4 by gamma-GTP during 60 minutes of exposure, and LTC4 itself has minimal direct effects on the ciliated cells.

Acetophenones↗

Age-related alterations in the auditory brainstem responses and the compound action potentials in guinea pigs.

The auditory brainstem response (ABR) and the eight nerve compound action potential (CAP) were measured using click click stimuli to investigate the age-related alteration in the auditory function in 66 guinea pigs consisting of four age groups. With advancing age, a gradual elevation of the thresholds in both the ABR and CAP was clearly seen, together with the prolonged latencies for waves I, II, III, and IV to clicks at 95 dBpeSPL in the ABR. There were some individual differences in either threshold elevation or latency prolongation of both the ABR and CAP in aged guinea pigs. These findings suggest that the effect of individual differences on degenerative aging processes of the auditory system should be considered in selected aged animals, although a significant elevation of the neural auditory threshold is clearly found with advancing age as a whole.

Action Potentials↗

Psychosomatic aspects of healthy young women with orthostatic dysregulation.

The Japanese Edition of the Cornell Medical Index-Health Questionnaire and the Yatabe-Guilford personality test (Y-G Test) was given to 56 young women (mean age 19.2 years) who were identified as having orthostatic dysregulation among a total of 280 healthy young women. The percentage classed as types III (possible neurotic) and IV (probable neurotic) according to the Health Questionnaire was 37.5% in the 56 with orthostatic dysregulation and 9.2% in the controls (n = 65). The percentage classed as types B and E, suggestive of emotional or psychological disturbance according to the personality test, was 59.0% in those with orthostatic dysregulation and 23.1% in the controls. These differences were statistically significant (P < 0.01). Furthermore, there was a significant correlation (P < 0.01) between the two test results for the frequency distribution of the 280 women. These results suggest a possibility that psychosomatic factors influence the occurrence of orthostatic dysregulation in young women, even if these subjects have not sought treatment for dizziness or vertigo, nor for psychosomatic disorders.

Adult↗

Leukotriene C4 inhibits ciliary activity in the presence of gamma-glutamyl transpeptidase.

We incubated human paranasal sinus mucosa in tissue culture with each of leukotrienes C4, D4, and E4 (LTC4, LTD4, and LTE4). Ciliary beat frequency (CBF) was measured photoelectrically, and the concentrations of leukotrienes in the incubation medium were determined over time. LTC4 significantly decreased CBF with 2-h, 4-h, and 8-h exposures to 10(-6) M, 10(-8) M, and 10(-10) M, respectively. Moreover, LTC4 dose dependently reduced CBF to 81.4% of the initial value after 6-h exposure to 10(-6) M, to 82.5% after 8-h exposure to 10(-8) M, and to 89.7% after 12-h exposure to 10(-10) M. LTD4 also exhibited progressive ciliary inhibition, while LTE4 had a minimal effect on CBF. In the medium, LTC4 was changed to LTD4 and further to LTE4. gamma-Glutamyl transpeptidase (gamma-GTP), an enzyme that converts LTC4 to LTD4, was detected in the mucosa. Serine-borate complex, an inhibitor of gamma-GTP, blocked the inhibitory effect of LTC4 on CBF. These findings suggest that LTC4 may induce ciliary inhibition indirectly by conversion to LTD4.

Borates↗

Effects of platelet activating factor on mucociliary clearance of the eustachian tube.

The effects of platelet activating factor (PAF) on mucociliary clearance of the eustachian tube were investigated both in vitro and in vivo. Normal ciliated epithelium was obtained from the eustachian tube of guinea pigs and incubated with PAF at concentrations ranging from 10(-10) to 10(-6) mol/L. Ciliary activity was observed under an inverted microscope and quantified photoelectrically. The PAF dose-dependently inhibited ciliary activity. One milliliter each of 10(-5) mol/LPAF, 10(-5) mol/L prostaglandin E2 (PGE2), 10(-5) mol/LPAF and PGE2, or the control solution (0.1 v/v% methanol-phosphate-buffered saline) was directly injected into the tympanic bullae of anesthetized chinchillas. The middle ear was examined by otomicroscopy, tympanometry, and auditory brain stem response in relation to time. The PAF delayed middle ear clearance, and the PGE2 augmented its delay. These findings suggest that PAF inhibits mucociliary clearance of the eustachian tube from the middle ear, and that PGE2 plays an important role in the augmentation of inflammatory disorders.

Animals↗

An ultrastructural study of goblet cells in rat nasal mucosa as revealed by the quick-freezing method.

In order to clarify the natural ultrastructure of goblet cells in the rat nasal mucosa, they were examined by the quick-freezing and freeze-substitution (QF-FS) or deep-etching (QF-DE) methods for comparison with conventional fixation methods. Some nasal mucosal tissues were unstimulated; others were stimulated with acetylcholine or substance P. The QF-FS method yielded fewer artefacts on transmission electron microscopy than conventional fixation methods. In the stimulated goblet cells, most of the secretory granules appeared to be loose in the matrix and more distorted in shape. By the QF-DE method, they were observed 3-dimensionally to be larger in size and aggregated together. In contrast, the secretory granules in the unstimulated goblet cells were mostly round and small, and separate from each other. It is concluded that the ultrastructure of secretory granules is artefactually modified by conventional fixation methods and that granule structure in goblet cells alters during the secretory process.

Acetylcholine↗

Investigation of oral alpha-streptococcus showing inhibitory activity against pathogens in children with tonsillitis.

The incidence of oral alpha-streptococcus with inhibitory activity against group A streptococcus, as a defense mechanism against bacterial infection in the oral cavity, was investigated in pediatric individuals with tonsillitis. Infection by group A streptococcus appeared to be common in children, because the detection rate of inhibitory alpha-streptococcus in healthy children as well as pediatric patients with tonsillitis was lower than in adults and elderly patients. In particular, the detection rate of these strains was predominantly low in patients with beta-streptococcus. Among pediatric patients scheduled for tonsillectomy, the detection rate of inhibitory alpha-streptococcus was low preoperatively. However, the rate was markedly increased after surgery. The high postoperative detection rate of these strains reflected the decreased incidence of group A streptococcal infection. The results of this investigation of bacterial interference between oral alpha-streptococcus and group A streptococcus suggested that surgical treatment is a more effective approach for improving the oral bacterial flora in children with recurrent tonsillitis.

Adult↗