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Biomedical subjects

S Kurihara

Publications and source records attributed to S Kurihara.

At least 145 records · Page 8Linked to original sources

[Phase II study of cisplatin in cervical and endometrial carcinomas].

A phase II group study of cisplatin for cervical and endometrial carcinomas was carried out in 19 institutes throughout Japan. The patients entered consisted of 62 women with cervical and 7 with endometrial carcinoma of whom 39 and 4 were evaluable, respectively. Cisplatin was administered in either of two regimens; 10-20 mg/m2 i.v., on days 1-5, or 50-100 mg/m2 i.v., on day 1, every 3 to 4 weeks. The responders comprised 4 CRs and 10 PRs for cervical carcinoma and 1 CR and 2 PRs for endometrial carcinoma, and the response rates were 35.9% and 75.0%, respectively. The response rates by histological classification were 39.4% (13/33) for squamous cell carcinoma and 16.7% (1/6) for non-squamous cell carcinoma. Response rates analysed by lesion site were 33.3% for primary tumors, 36.8% for local lesions and 33.3% for metastases. Furthermore, the response rate among patients without any prior chemotherapy was 44.4% vs. 16.7% for those with prior chemotherapy. Adverse effects included nausea and vomiting (95.3%), anorexia (93%), anemia (72.1%), leucopenia (60.5%) and elevation of BUN (16.3%). Adverse effects were tolerable. We concluded from these results that cisplatin is among the most efficacious and useful drugs against cervical (and endometrial) carcinoma(s).

Adenocarcinoma↗

[Phase II study of 5-FU tablets in cancer of the uterine cervix].

A phase II study of 5-FU tablet for 52 patients with cancer of the uterine cervix was undertaken by a cooperative study group consisting of 13 institutions. The clinical response rate in 44 evaluable cases was 31.8% (CR: 3 cases, PR: 11 cases, MR: 2 cases, NC: 19 cases and PD: 9 cases). Efficacy rates of 5-FU tablet according to lesion sites were 44.4% in the uterine cervix, 42.9% in the vaginal wall and cut vaginal end, 25.0% in the lymph nodes and 16.7% in the lung. Histologically, the effectiveness rate was 26.9% for large-cell, non-keratinizing-type-carcinoma, 42.9% for small-cell, non-keratinizing-type, and 60.0% for the keratinizing-type of squamous cell carcinoma. One of three adenocarcinoma cases (33.3%) showed improvement. Some adverse effects were observed in 16 (32.0%) of 50 evaluable cases. A large proportion of the adverse effects were gastro-intestinal disorders, such as nausea, vomiting and anorexia. These results suggested that 5-FU tablet is a useful chemotherapeutic agent against carcinoma of the uterine cervix.

Adult↗

Angiotensin I converting enzyme activity in the kidney of bullfrog (Rana catesbeiana).

In the present investigation, the occurrence of angiotensin I converting enzyme (EC 3.4.15.1; ACE) was first demonstrated in the kidney of bullfrog (Rana catesbeiana). Namely, a large amount of hydrolyzing activity toward N alpha-hippuryl-L-His-L-Leu-OH (HHL), a synthetic substrate of ACE, was detected in a 100,000 X g pellet fraction of the bullfrog kidney. The renal HHL hydrolyzing enzyme was solubilized from the 100,000 X g pellet with sodium deoxycholate. The solubilized bullfrog renal enzyme liberated H-His-Leu-OH from HHL. The enzyme activity was strongly activated by NaCl and slightly activated by cobalt sulfate in the presence of NaCl. These properties of the bullfrog renal enzyme agreed well with those of mammalian ACE previously reported. The bullfrog renal HHL hydrolyzing activity was completely inhibited by typical ACE inhibitors, ethylenediamine tetraacetic acid (10(-3) M), captopril (10(-5) M), SA-466 (10(-5) M) and MK-422 (10(-6) M). Furthermore, [Ile5]-angiotensin I converting activity was also detected in this enzyme fraction of bullfrog kidney and this converting activity was completely inhibited by MK-422 (10(-6) M). Thus, enzyme activities having characteristics of ACE were detected in the 100000 X g pellet of bullfrog kidney. We also detected [Val5, Asn9]-angiotensin I (bullfrog angiotensin I) converting activity in the bullfrog renal extract. This converting activity was also completely inhibited by MK-422 (10(-6) M).

Animals↗

[Penetration of cefoperazone into the exudate of the retroperitoneal space after (semi-)radical hysterectomy].

The purpose of the study was to examine the penetration of cefoperazone (CPZ) into the exudate of retroperitoneal space after (semi-)radical hysterectomy in patients with uterine carcinoma and to evaluate the suitability of its prophylactic use. Two grams of CPZ was administered by intravenous infusion over 1 hour just after the operation and the same dose was repeated every 12 hours for 3 consecutive days. The exudate was collected from the abdominal drainage for every 3 hours for measurements of hemoglobin, total protein and CPZ levels. Concentrations of CPZ in exudate samples were found to remain above the MICs for major causative organisms of the inflammation in both groups of patients of radical (14 cases) and semiradical (5 cases) hysterectomy. On the operative and 1st days, exudate CPZ level in the group of semiradical hysterectomy patients showed higher than that in the group of radical hysterectomy patients. But on the 2nd day, there was no significant difference in exudate CPZ level between these 2 groups. The above results indicated that the presence of blood in the retroperitoneal space might affect the concentration of the antibiotic in the exudate. From these findings, it is concluded that the present dosage regimen is efficient to prevent the postoperative infection after (semi-)radical hysterectomy.

Bacterial Infections↗

[Study of coagulum pyelolithotomy].

Coagulum pyelolithotomy was carried out on 20 patients from January, 1980 to April 1984. Nephrolithotomy was jointly carried out on 4 of them, but residual stones were observed in 4 cases (20%). No side effect such as hepatitis was observed in any cases. While inferring the cause of residue, experimental study was made on tension, coagulation time and mixing method in respect to coagulum formation. In the experiment on tension, no significant difference was observed when thrombin concentration was changed, but when calcium was added, tension increased 4 fold. As thrombin concentration rose, so shortened the coagulation time. It was inferred that a better coagulum is made available if fibrinogen and thrombin are mixed outside the kidney.

Adult↗

Effects of rapid cooling on mechanical and electrical responses in ventricular muscle of guinea-pig.

The effect of rapidly lowering bathing solution temperature from 36.5 +/- 0.5 degrees C to various low temperatures was examined in guinea-pig ventricular muscle to explore the possible role of intracellular Ca2+ store sites in excitation-contraction coupling. Rapid cooling from 36.5 +/- 0.5 degrees C to below 18 degrees C caused contracture (rapid cooling contracture, r.c.c.) with subthreshold depolarization for contraction, if electrical stimulation was applied before cooling. R.c.c. peak tension depended on cooling temperature, and pre-cooling stimulation frequency and duration. R.c.c. induced after pre-cooling stimulation was enhanced by increased extracellular Ca2+ ( [Ca2+]o) and decreased by reduction of [Ca2+]o. Co2+ (2-4 mM) added to the HEPES-buffered Krebs solution, which suppressed the action potential plateau and inhibited twitch response, did not abolish r.c.c. after pre-cooling stimulation at high frequency. Reduction of extracellular Na+ concentration ( [Na+]o) before cooling enhanced r.c.c., and even in non-stimulated preparations, incubation in low [Na+]o below 68.8 mM for 20 min produced r.c.c. R.c.c. was superimposed on the tonic component of the K+ contracture, after a quiescent preparation has been depolarized beyond -40 mV by addition of solid KCl to normal Krebs solution. The relation between r.c.c. tension and membrane potential was shifted to the left along the voltage axis by reducing [Na+]o and shifted to the right by decreasing [Ca2+]o. Results suggest that well-developed intracellular Ca2+ store sites could sequester enough Ca2+ to generate tension by an energy-dependent process which had been loaded mainly by a voltage-dependent Na+-Ca2+ exchange mechanism and Ca2+ current, and that rapid cooling could cause Ca2+ release from the intracellular store sites with little contribution to membrane excitation in the guinea-pig ventricular muscle.

Action Potentials↗

Change in intracellular calcium ion concentration induced by caffeine and rapid cooling in frog skeletal muscle fibres.

In a single skeletal muscle fibre treated with concentrations of caffeine below threshold for caffeine contracture, rapid lowering of the temperature of the bathing solution from 18 degrees C to below 5 degrees C induced a contracture (rapid cooling contracture). Intracellular Ca2+ concentration ([Ca2+]i) was recorded during rapid cooling contracture using aequorin. Low concentrations of caffeine often caused a slight elevation of the light signal in resting muscle without detectable tension. During rapid cooling contracture, the change in light signal occurred in three phases. The first phase was a transient change of [Ca2+]i accompanying slight tension. During the second phase, the light signal slowly increased as cooling produced maximum tension development. The third phase was an additional light signal induced after the second phase, even though the tension was saturated. The second and third phases were more sensitive to low concentrations of procaine (0.2-0.5 mM) than the first phase. Synchronous oscillations of light and tension were often observed during the second phase. The light signal during rapid cooling contracture was only slightly affected by long incubation in Ca-free or Ca-rich solutions. These results are interpreted as follows. A low concentration of caffeine elevates cytoplasmic resting Ca2+ level without tension development. The oscillations of light and tension often observed in the second phase might represent a cyclic release of Ca2+ from the sarcoplasmic reticulum (s.r.). The third phase is considered to be due to a massive Ca2+ release by a Ca-induced Ca-release mechanism which might be similar to that in skinned fibres. The second phase is probably essential for generation of rapid cooling contracture tension and the third phase represents an excess Ca2+ for tension development.

Aequorin↗

[Production and characterization of monoclonal antibody to uterine cervical cancer cell line SKG-IIIa].

By means of an immunization procedure using intact living cells, the established uterine cervical epidermoid cancer cell line SKG-IIIa, a monoclonal antibody (Mab) which reacts with uterine cervical epidermoid cancer cells was obtained. The Mab was of IgG2a subclass. Immunohistochemically the Mab reacted with uterine cervical epidermoid cancer cells (17 out of 25). At the same time, it reacted with a basal layer of normal squamous epithelium, surface mucus secreting cells and parietal cells in stomach and kidney uriniferous tubules. The Mab reacted with the cell surface epitope on HeLa cells to the same extent as on SKG-IIIa cells, but on CCD18-Lu cells (normal diploid) to about one-half as much. The results of an inhibition test using a competitive reaction between Mab and conventional polyclonal antibody indicated that the Mab didn't react with 39 kinds of human serum proteins such as albumin, transferrin, IgG, fibrinogen, lysozyme and some tumor markers. Immunohistochemical staining also revealed that the Mab didn't recognize human blood group substances (A,B,H type, Lewis's a,b type). Treatment of SKG-IIIa cells with a mixture of glycosidases neuraminidase or periodate didn't change the reactivity to the Mab, suggesting that the epitope didn't reside in sugar chains.

Antibodies, Monoclonal↗

Quantitative analysis of the whiteness of the atypical cervical transformation zone.

The whiteness of the atypical cervical transformation zone is considered one of the important factors for grading colposcopic findings. The whiteness was measured on photographs taken with a newly developed method that uses double polarizing filters fixed in a rectangular position. This method eliminates highlights and makes it possible to compare the whiteness of different cases according to the same standard. The whiteness after acetic acid application and its diminution rate after four minutes were measured. Significant differences in whiteness were proven to exist between grade 1, 2 and 3 cervical intraepithelial neoplasia, between squamous metaplasia and carcinoma in situ (CIS) and between dysplasia and micro-invasive carcinoma. Significant differences in the diminution rate were revealed between each grade and between squamous metaplasia and CIS.

Carcinoma↗

Changes in [Ca2+]i induced by rapid cooling of single skeletal muscle fibres treated with low concentration of caffeine.

In single skeletal muscle fibres treated with low concentration of caffeine, lowering the bathing solution temperature from 18 degrees C to below 7 degrees C increased [Ca2+]i in three phases depending on caffeine concentration and temperature. Tension could be fully developed (rapid cooling contracture, RCC) by the second phase of the released Ca2+. The second and third phases were inhibited by low concentrations of procaine, and the first phase was blocked by a higher one. RCC was observed even in Ca2+-free solution. The mechanism of [Ca2+]i changes and RCC during cooling was discussed.

Aequorin↗

Effects of enflurane on excitation-contraction coupling in frog skeletal muscle fibers.

The effect of enflurane on the excitation-contraction (E-C) coupling of frog skeletal muscle fiber was studied. Low (19.13 +/- 0.70 mg%) and high (108.52 +/- 4.52 mg%) concentrations of enflurane did not cause substantial changes of the resting membrane potential but a high concentration of enflurane reduced the peak of action potentials and prolonged the duration measured at 50% peak amplitude. During the twitch response, enflurane reduced the peak response of light signal measured with calcium-sensitive photoprotein, aequorin, but peak tension was not diminished by a low concentration of enflurane. A high concentration of enflurane remarkably inhibited both light signal and tension. During tetanus, a low concentration of enflurane partially abolished light signal and tension. At the high concentration, this inhibitory effect was pronounced and action potentials were only observed in the initial phase of tetanic stimulation. Enflurane enhanced the increase of light signal observed in rapid cooling contracture. In glycerinated muscle fiber, enflurane shifted the pCa-tension relation to the left in low calcium and suppressed maximally activated tension at high calcium concentration. Inhibitory effect of enflurane on light signal in twitch response without abolition of action potential suggests that enflurane might inhibit E-C coupling in frog skeletal muscle fiber (but it enhances direct calcium release from SR induced by caffeine) and increase calcium sensitivity of contractile element.

Action Potentials↗

The effects of caffeine on tension development and intracellular calcium transients in rat ventricular muscle.

The effects of caffeine on tension and intracellular [Ca2+] were investigated in rat ventricular muscle using the Ca2+-sensitive photoprotein, aequorin. Contracture was induced by rapid application of 0.5-10 mM-caffeine solution at 20 degrees C. In normal Tyrode solution at 8 degrees C, or in Na+-deficient solution in which Na+ was isotonically replaced by sucrose, peak tension of caffeine contracture was potentiated and relaxation was prolonged. Caffeine contracture could not be induced immediately after a prior contracture. Repriming time was 10 min in Tyrode solution, and was much shorter in Na+-deficient solution or in high-K+ solution containing 105.9 mM-K+. Caffeine prolonged the plateau of action potential dose dependently. At low temperature, prolongation of the plateau phase by caffeine was more marked. Twitch tension showed a triphasic change after application of caffeine; peak tension transiently increased in a potentiating phase (P phase), and then decreased below control level in an inhibitory phase (I phase) followed by gradual recovery in a recovery phase (R phase). The effects of caffeine on the Ca2+ transients during a twitch were also complex, depending on time after application and dose of caffeine. In low caffeine concentration (below 0.5 mM) the peak of the Ca2+ transient was potentiated in the I phase, although the peak tension was suppressed. At high concentration (above 3 mM) the peaks of both the Ca2+ transient and twitch tension were suppressed. In every concentration of caffeine tested (0.1-5 mM), time to the Ca2+ transient and twitch tension peaks was prolonged, and the falling phases of both were delayed. Caffeine might release Ca2+ from intracellular store(s) and enhance the slow inward current. The Ca2+ transient obtained in this study clearly indicate that the prolonged time to peak tension in the presence of caffeine is due to the slow rise of intracellular [Ca2+] and prolonged time to peak of the Ca2+ transient. It is also quite possible that caffeine modulates the Ca2+ sensitivity of a contractile system in dose- and time-dependent manners.

Action Potentials↗

Prurigo pigmentosa affecting the forehead.

A little-known dermatosis, prurigo pigmentosa, is characterized by itchy reddish lesions and gross reticular pigmentation which occurs mainly on the trunk. Histologically, it is characterized by lichenoid tissue reaction. We present a 23-year-old male patient who showed typical eruption not only on the trunk but also on the forehead. Although the etiology remains to be explained, this unusual distribution of the eruption might help to know the real cause of this peculiar disorder.

Adult↗