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Biomedical subjects

S Komiyama

Publications and source records attributed to S Komiyama.

At least 19 recordsLinked to original sources

Disturbance of regulation of sodium by cis-diamminedichloroplatinum in perilymph of the guinea pig cochlea.

We studied the acute effects of cis-diamminedichloroplatinum (CDDP) on the cochlear partition and inner ear fluid in the guinea pig. At 48 hours after the administration of a single intramuscular injection of CDDP, 12.5 mg/kg of body weight, the endocochlear resting potential (EP) was significantly decreased to 32.1 +/- 1.8 mV in the treated animals, versus 80.6 +/- 1.0 mV in the control animals. There was a significant rise in potassium (K+), sodium (Na+), and chlorine (Cl-) in the endolymph of the animals treated with CDDP as compared with the control animals. Only Na+ was found to increase significantly in the perilymph, reaching more than twice the level of the control animals; both K+ and Cl- remained within the normal range. Serum electrolytes also remained within the normal range. Evaluation of modified ionic permeabilities across the endolymph-perilymph barrier showed an apparent increase in Na+ permeability and a normal range of K+ and Cl- permeabilities. Histopathologic examination of the cochlea showed a moderate collapse of the endolymphatic space, with atrophy of the stria vascularis and destruction of the outer hair cells. The findings suggest that the acute changes produced in the cochlea by administration of CDDP were attributable to a breakdown in the regulation of Na+ metabolism in the perilymph.

Animals

Giant tumor formed by nodular fasciitis of the pharynx: a case report.

Nodular fasciitis caused a benign tumor which is composed of fibrous tissue. The most commonly affected site is the upper extremity, which accounts for half of all cases. Ten to 20% of the lesions occur in the head and neck area, most of which are subcutaneous. We report a case of nodular fasciitis, which presented as an unusually large submucosal tumor of the pharynx. The tumor was extended from the retropharyngeal to the parapharyngeal space, and it was measured 8 x 4 x 3 cm in size. Since nodular fasciitis is known for the spontaneous regression, the tumor was transorally debulked by the use of YAG laser.

Adult

Coexistence of MALT-type lymphoma and squamous cell carcinoma of the larynx.

A 66-year-old Japanese man was diagnosed as having a MALT-type lymphoma by histopathological examination. The lesion involved the vocal folds bilaterally, occupying the larynx and extending beyond it, as shown by computed tomography (CT). A course of radiation therapy with moderate doses was given. Six months later, a squamous cell carcinoma was found in the larynx and total laryngectomy was then performed. The patient remained well, without recurrence, 46 months after the operation. thus, MALT-type lymphoma may coexist with a squamous cell carcinoma of the larynx.

Aged

Single channel recordings of calcium currents in chick cochlear hair cells.

Single Ca2+ channel currents were recorded from chick cochlear hair cells by using cell-attached patches. The elementary current was about -2 pA at 70 mV positive to the resting potential (R.P.+ 70 mV); the slope conductance over a 40 mV voltage range was 24 pS. The open time histogram was reasonably well expressed by a single exponential function, while the closed time histogram was expressed by a sum of two exponential functions. The Ca2+ channel was activated around R.P.+ 60 mV and the average ensemble current did not decay during 130 ms depolarization, suggesting that the Ca2+ channel in chick cochlear hair cells is the L-type. The Ca2+ channel has three modes of gating behaviour, expressed as current records with brief openings (mode I), no openings (mode 0), or long-lasting openings and very brief closings (mode 2).

Animals

[A prospective randomized trial of adjuvant chemotherapy with UFT for head and neck carcinoma. Head and Neck UFT Study Group].

A prospective randomized trial was performed in 67 institutions for the purpose to evaluate the efficacy of adjuvant chemotherapy after radical treatment of head and neck carcinoma. A comparison was made between the following two groups; one-year oral administration of UFT, 300 mg/day, after radical treatment (UFT group); and a non-treatment group. Patients were classified under the following three categories; 1) stage II-IV, receiving radical surgery; 2) stage II, receiving radical radiotherapy; and 3) nasopharyngeal cancer. The numbers of cases were 424, 111 and 25, respectively, and they were randomized into two groups. The numbers of eligible cases were 398, 105 and 25, respectively. Statistical analysis was performed in the cases receiving radical surgery and in those receiving radical radiotherapy. As the results, in cases receiving radical surgery no significant difference was observed in 3-year survival rates (77.9% for UFT group vs 72.9% for non-treatment group) or 3-year relapse-free rates (73.4% for UFT group vs 66.2% for non-treatment group) between the two groups. However, the distant relapse rate was significantly lower in the UFT group than in the non-treatment group (7.9% vs 14.6%; p = 0.034). In the cases receiving radical radiotherapy, no significant differences was observed in either 3-year survival rates or 3-year relapse-free rates. Thus it was suggested that UFT maintenance therapy might suppress the distant metastasis after radical surgery. We considered a further confirmative trial for patients at high risk of distant metastasis after radical surgery to be advisable.

Administration, Oral

Cisplatin blocks mechano-electric transducer current in chick cochlear hair cells.

The effects of cisplatin (cis-dichlorodiammine platinum II, CDDP) on the mechano-electrical transduction (MET) current were investigated with a whole-cell patch-electrode voltage clamp technique in dissociated cochlear hair cells of chicks. CDDP blocked the MET channel in a dose- and voltage-dependent manner. At -50 mV, CDDP blocked the MET channel with a Hill coefficient of approximately 2 and a dissociation constant (KD) of 1.5 x 10(-3) M. The kinetics of CDDP blockade consist of a voltage-independent and a voltage-dependent component.

Animals

Differentially potentiating effects by dipyridamole on cytotoxicity of 5-fluorouracil against three human maxillary cancer cell lines derived from a single tumor.

Dipyridamole (DPM), an inhibitor of nucleoside transport, is a unique potentiator of 5-fluorouracil (5-FU). We examined the combined effects of DPM and 5-FU on three cell lines (IMC-2, IMC-3, IMC-4) derived from a single tumor of a patient with maxillary cancer. DPM at 1.0-2.0 microM potentiated the cytocidal action of 5-FU > 20-fold against IMC-2 cells, while DPM at 10-20 microM potentiated the action of 5-FU against IMC-3 cells by 2-fold and against IMC-4 cells by approximately 4-fold. We examined why DPM differentially potentiated 5-FU against the three cell lines. The three maxillary cell lines showed heterogeneous sensitivities to the combination of 5-FU and DPM. We compared intracellular metabolism of 5-FU in IMC-2, IMC-3 and IMC-4 cells by HPLC. Determination of 5-FU metabolites demonstrated that cellular contents of 5-fluorodeoxyuridine monophosphate (FdUMP) were 104.66, 15.35 and 61.5 fmol/10(6) cells in IMC-2, IMC-3 and IMC-4 cells, respectively, in the presence of 10 microM DPM when the three cell lines had similar levels (0.21-0.33 fmol/10(6) cells) of FdUMP in the absence of DPM. By contrast, cellular levels of 5-FU and 5-fluorouridine triphosphate (FUTP) were not appreciably changed by DPM in three cell lines. The cellular level of thymidylate synthase mRNA in IMC-2 cells was found to be about one-fifth of that in IMC-3 and IMC-4 cells. The differential effects of DPM on the potentiation of 5-FU cytotoxicity might be closely related to the cellular levels of FdUMP and its target enzyme, thymidylate synthase in three human maxillary cancer cell lines.

Cell Survival

Heterogeneity in epidermal growth factor responsiveness and tumor growth of human maxillary cancer cell lines.

We have established three cell lines (IMC-2, IMC-3, and IMC-4) from a human maxillary tumor, which exhibited different sensitivities to epidermal growth factor (EGF). It was inhibitory to colony-forming abilities of IMC-3 and IMC-4 cells in culture, while it affected that of IMC-2 cells slightly if at all. The differential sensitivities to EGF among the three cell lines were reproducibly observed when several cell sublines were further established from tumors appearing in nude mice. Saturation-binding kinetics with 125I-EGF showed similar levels of EGF-binding activities among the three cell lines. However, IMC-2, IMC-3, and IMC-4 showed almost similar sensitivities to cisplatin. Autophosphorylation of EGF receptor in the presence of EGF proceeded at similar levels among the three cell lines. Tumor growth was followed in nude mice when IMC-2, IMC-3, and IMC-4 at 1 x 10(7) cells were inoculated. The IMC-2 tumors enlarged at much faster rates than the other two cell lines. The IMC-4 tumors showed very slow growth rates, and IMC-3 tumors enlarged at an intermediate rate. These data suggest that the maxillary tumor used comprised cell populations that differed in their growth behaviors in response to EGF.

Carcinoma, Squamous Cell

[An early phase II clinical study of cis-diammine glycolato platinum, 254-S, for head and neck cancers].

An early phase II clinical study of 254-S, a new anticancer platinum complex, for head and neck cancer was conducted by the 254-S Head and Neck Cancer Study Group consisting of 10 institutions. Based on the results obtained in the phase I study, 254-S was administered at 100 mg/m2 by 60 min intravenous drip infusion after being dissolved in 300 ml of 5% xylitol. In principle, the 254-S administration was repeated at least 2 times at 4 week intervals. Hydration was performed, if needed. All 24 cases registered were regarded as complete cases evaluable for tumor response. Complete response (CR) was observed in 4 patients (16.7%), partial response (PR) in 5 (20.8%), no change (NC) in 11 and progressive disease (PD) in 4, for a 37.5% response rate. Three CR and 3 PR (40.0%) were obtained in 15 patients with prior chemotherapy, including 1 CR and 2 PR (33.3%) in 9 patients previously treated with cisplatin. Side effects were observed in 19 patients (79.2%). Major toxic effects were hematotoxicity, including thrombocytopenia (58.3%), leukopenia (58.3%) and anemia (33.3%), and gastrointestinal toxicity, including nausea and vomiting (45.8%) and anorexia (37.5%). Abnormal parameter changes on renal function were found in 2 patients (8.3%). Based on these results, it was concluded that 254-S is potentially a useful anticancer agent for the treatment of head and neck cancer, and should be further investigated in a late phase II clinical study.

Adenocarcinoma

[A late phase II clinical study of cis-diammine glycolato platinum, 254-S, for head and neck cancers].

A late phase II clinical study of 254-S, a new anticancer platinum complex, for head and neck cancer was conducted by the 254-S Head and Neck Cancer Study Group consisting of 31 institutions. As in the early phase II study for head and neck cancers, 254-S was administered at 100 mg/m2 by 60 min intravenous drip infusion, repeated at least twice at 4-week intervals. Of 80 cases registered, 66 were regarded as complete cases evaluable for tumor response. Complete response (CR) was observed in 7 patients (10.6%), partial response (PR) in 22 (33.3%), no change (NC) in 24 and progressive disease (PD) in 13, for a 43.9% response rate. Two CR and 11 PR (37.1% response rate) were obtained in 35 patients with prior chemotherapy, including 2 CR and 7 PR (33.3% response rate) in 27 patients previously treated with cisplatin. Of 70 patients evaluable for toxicity, side effects were observed in 60 patients (85.7%). Major toxic effects were hematotoxicity, including leukopenia (62.9%), thrombocytopenia (40.0%) and anemia (45.7%), gastrointestinal toxicity, including nausea and vomiting (64.3%), and anorexia (47.1%); grade 3 or 4 thrombocytopenia was found in 20.0% of the patients, and this toxicity was regarded as the dose limiting factor. Nephrotoxicity observed was mild and infrequent. Based on these results, it was concluded that 254-S is a very useful anticancer agent for the treatment of head and neck cancer.

Adenocarcinoma

The response to epidermal growth factor of human maxillary tumor cells in terms of tumor growth, invasion and expression of proteinase inhibitors.

Three cancer cell lines, IMC-2, IMC-3 and IMC-4, were established from a single tumor of a patient with maxillary cancer. We examined responses to epidermal growth factor (EGF) of these 3 cell lines with regard to cell growth and tumor invasion. The growth rate of IMC-2 in nude mice was markedly faster than that of the IMC-3 and IMC-4 cell lines. Assay for invasion through fibrin gels showed significantly enhanced invasive capacity of IMC-2 cells in response to EGF, but no change for IMC-3 and IMC-4 cells. We examined response to EGF of IMC-2 cells with regard to expression of a growth-related oncogene (c-fos), proteinases and their inhibitors. Expression of c-fos was transiently increased in IMC-2 cells at rates comparable to those seen in the 2 other lines in the presence of EGF. There was no apparent effect of EGF on the expression of urokinase-type plasminogen activator and 72-kDa type-IV collagenase in IMC-2 cells. In contrast, EGF specifically enhanced the expression of plasminogen activator inhibitor-I (PAI-I) and tissue inhibitor of metalloproteinases-I (TIMP-I) in IMC-2 cells. Our data suggest that proteinase inhibitors or other related factors may play an important role in tumor growth and invasion in response to EGF.

Animals

Bio-feedback and the yawning breath pattern in voice therapy: a clinical trial.

A breathing technique, or effective breath method is important for both singers and speakers for effective vocalization, and also useful for helping people with a voice problem. Here a diaphragm support breath pattern was used in voice therapy for patients with vocal nodules, recurrent laryngeal nerve paralysis, and incomplete glottal closure. Singing teachers use a technique, called the diaphragm breath support. This is called the yawning breath pattern (YBP) in our voice clinic and is used in teaching the patients with some kinds of voice disorder. In order to correct patients' breath pattern, an equipment system was designed to check their breath patterns conveniently in voice therapy practice. A respiratory kinematic sensor which connected to a TV monitor was attached to the patients' rib cage near the diaphragm, and by bio-feedback, patients could observe and adjust their breath pattern to the desired pattern during vocalization. In each of the 10 outpatient sessions, the patients performed for 20 to 30 min, and were instructed to practice at home for 3 or more times daily. The YBP method was applied to 91 patients, 17 males and 74 females, with ages ranging from 17 to 79 years. Of the 91 patients 41 had vocal nodules, 20 had recurrent laryngeal nerve paralysis and 30 had incomplete glottal closure associated with chronic laryngitis and sulcus vocalis. Most of the patients could master the YBP technique successfully. The higher the patients' ability to master the YBP was the better the results of both voice tests and subjective evaluation. The scientific background of the YBP method and its clinical effects in voice therapy was reviewed.

Adolescent

[Clinical evaluation of hypopharyngeal cancer].

Clinical results of cases of hypopharyngeal carcinoma treated from 1966 to 1990 at Kyushu University Hospital were investigated. In 1966-1972, all cases were treated with only radical operation. We used FAR therapy since 1972, and preoperative chemotherapy (CDDP and Peplomycin) in addition to FAR therapy since 1984. The crude five-year survival rate of the operative therapy-group (25 cases in 1966-1972) was 24%, and that of the FAR therapy-group with or without operation (47 cases in 1972-1980) was 38%. Although it was cumulative survival rate by Kaplan-Meier's method, the five-year survival rate of the group (16 cases in 1984-1990) treated with a combination of FAR therapy, preoperative-chemotherapy, and operation was 76%. The improvement in the survival rate and the role of preoperative treatment (FAR therapy and chemotherapy) are discussed.

Antineoplastic Combined Chemotherapy Protocols

[Radiotherapy and chemotherapy in stages I and II non-Hodgkin's lymphomas of Waldeyer's ring].

Sixty-four patients with stages I and II non-Hodgkin's lymphomas (NHL) involving Waldeyer's ring treated between 1970 and 1987 were reviewed. Patients with stage II NHL were subdivided into stage II 1 (limited type) and stage II2 (advanced type) from the state of neck nodes. Stage II1 was defined as involvement of unilateral cervical nodes less than 4 cm in diameter as well as Waldeyer's ring involvement. Other stage II cases were classified as stage II2. All 17 patients with stage I NHL were treated with radiation therapy alone. Their diseases were well controlled, and none of them died of causes related to the lymphoma. Among 14 patients with stage II1 NHL, the 5-year survival rate for the 9 patients treated with radiation therapy alone was 87.5%. Until 1982, 19 of 21 patients with stage II2 NHL treated with radiation therapy alone or radiation therapy and adjuvant chemotherapy (VEMP or COPP) died within 5 years mainly of disseminated diseases. Since 1983, CHOP has been used as the main treatment as well as radiotherapy for the 12 stage II2 NHL patients. So far, only 3 of them relapsed and 2 of them died of causes related to the lymphoma. Only 1 of these 12 patients was T-cell lymphoma compared to 7 of 9 stage II2 patients before 1982. This suggests that patients with stage I and those with limited stage II can be safely treated with radiotherapy. Also aggressive chemotherapy as well as radiotherapy should be used for patients with advanced stage II NHL involving Waldeyer's ring.

Adult

Establishment of tumor cell lines from a patient with head and neck cancer and their different sensitivities to anti-cancer agents.

The authors established five cell lines from a human head and neck tumor. The five cell lines (HC-2, HC-3, HC-4, HC-7, and HC-9) exhibited different sensitivities to Adriamycin, cisplatin, bleomycin, 5-fluorouracil, vincristine, and daunomycin. The D50 was 200 ng/ml Adriamycin (doxorubicin) for HC-7 and 45 ng/ml for HC-2. At the inception of long-term culture (11 months) in the absence of any drug, the sensitivity to Adriamycin of HC-7-5 (subcloned from HC-7) was 3.4 times greater than that of HC-2-6 (subcloned from HC-2); by 11 months, it decreased to 1.6 times that of HC-2-6. The cytocidal action of Adriamycin on HC-2-6 and HC-7-5 was potentiated when Adriamycin was combined with verapamil or cepharanthine. Cepharanthine also potentiated daunomycin and vincristine (VCR) against HC-2-6 and HC-7-5 cells, and it almost completely overcame drug-resistance to daunomycin and vincristine in HC-7-5/VCR, a multidrug-resistant variant isolated after long exposure to vincristine of HC-7-5 cells in culture. The cellular accumulation of [3H]-daunomycin by HC-7-5 cells was about 70% that of HC-2-6 cells. By Northern blot analysis, using a multidrug-resistance gene (mdr-1) probe, neither HC-2-6 nor HC-7-5 expressed the mdr-1 gene, but HC-7-5/VCR or other multidrug-resistant variants showed active expression of the mdr-1 gene. Differential sensitivities among the five cell lines to 5-fluorouracil, cisplatinum, and bleomycin appear to be mediated through other mechanism beside the mdr-1 gene.

Alkaloids

[Study on determination of the imaginary axis of the tooth crown. 1. Measuring procedure].

The state of inclination and the change under various conditions of the imaginary axis of the tooth crown of upper jaw and lower jaw right and left first molar can be determined by the measuring apparatus and method of this study. 2. The measurement error of this method was not more than 0.1 degree. This value was sufficient for the purpose of this study.

Molar