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Biomedical subjects

S Tsuchida

Publications and source records attributed to S Tsuchida.

At least 199 records · Page 11Linked to original sources

[Human papilloma virus (HPV) antigens and DNA in dysplasia and carcinoma of the uterine cervix].

Routinely paraffin-embedded sections of dysplasia, carcinoma in situ (CIS) and invasive (squamous) carcinoma of the cervix were studied to determine the participation of human papilloma virus (HPV) in these tissues. Morphological observation (1,059 cases) revealed condylomatous changes to reach 54% in dysplasia, 25% in CIS and 25% in invasive carcinoma. Condylomatous changes were also found to be 25 to 40% in the non-cancerous epithelia adjacent to in situ or invasive carcinomas. The immuno-peroxidase-PAP-method using anti-HPV serum was applied to 98 selected sections in which condylomatous changes were morphologically observed. HPV antigens were found to reach 56% in dysplasia, 42% in CIS and 35% in invasive carcinoma, and this result suggested that the morphologically observed condylomatous changes did not always coincide with virus maturation in the infected cells. By means of the in situ hybridization technique, HPV type-6, -11, -16 and -18 DNAs were all detected in dysplasia sections, whereas HPV type-16 DNA was demonstrated distinctively at a high rate among in situ and invasive carcinomas.

Antigens, Viral↗

[Estrogen production in epithelial tumors of the ovary--clinical and endocrinological study in postmenopausal women].

Estrogen-producing activity of common epithelial tumors (54 cases) and metastatic tumors (4 cases) of the ovary was clinically and endocrinologically studied in postmenopausal patients. High serum concentrations of E1 (greater than or equal to 50 pg/ml) and E2 (greater than or equal to 30 pg/ml) were demonstrated in 78% in the group of postmenopausal patients. Mucinous tumors were more commonly associated with high estrogen levels than serous tumors. Patients with malignant tumors more frequently have a high level of serum estrogen than those with benign tumors. Estrogen decreased to normal after complete resection of the tumor, but returned to the abnormal range following a recurrence. The local-peripheral gradient of the estrogen level was noted by measuring the estrogen concentration in the blood of the affected ovarian and peripheral veins at the time of laparotomy. These results indicated that serum estrogen in the patient was originally produced in the ovarian tumor mass. The increased estrogen were reflected in such target tissues as the endometrium and vaginal mucosa. Proliferation, hyperplasia, atypical hyperplasia and even a case of carcinoma of the endometrium were observed in patients with ovarian tumors. An increase in the karyopyknotic index (KPI) of the vaginal smear, as well as uterine bleeding, could be an important signs of asymptomatic ovarian tumors in postmenopausal women.

Biomarkers, Tumor↗

[Anti-cancer drug resistance and glutathione S-transferases].

Glutathione S-transferase (GST) is a family of multimolecular forms with multi-functions for detoxication of drugs, and certain GST forms have been reported to concern multidrug resistance (MDR) mechanisms of neoplastic cells to anticancer drugs. In this paper, recent studies of GSTs concerning MDR are briefly reviewed, and the problems to be clarified are discussed. The reduced glutathione (GSH) is known to play important roles in the inactivation (detoxication) of the anticancer drugs. Most of them, especially alkylating agents, are conjugated with GSH by GSTs and detoxified, and the peroxides from drugs such as adriamycin are also reduced with GSH and detoxified by the GSH peroxidase activity of certain GST forms. Rat GST-P (GST 7-7) and human GST-pi, both of which belong to Class pi in the species-independent classification of GST, have been known as a marker enzyme for rat and human (pre) neoplastic lesions, respectively. GST-P is increased in rat hepatic preneoplastic foci resistant to cytotoxic agents. GST-pi is also increased not only in cancer cells such as colon carcinoma and non-small cell lung carcinoma, which exhibit "natural resistance" to anticancer drugs, but also increased in breast, ovarian and other tissue carcinomas with increased "acquired resistance" to certain drugs. A few research groups have attempted to confirm by transfection of a vector expressing a GST form such as GST-pi into non-resistant cell lines whether there is a direct relationship between the expression of a specific GST form and the appearance of MDR. However, MDR did not always appear. Recently, it was found in our laboratory that GST-P, GST-pi and even mouse GST II in Class pi, all are very strongly inactivated by SH-modifiers and active oxygens, indicating that these properties may be useful for overcoming MDR, if the forms really are involved with MDR.

Animals↗

[Estrogen production in epithelial tumors of the ovary--localization of estrogen-synthesizing cells].

The origin of the elevated serum estrogen in postmenopausal patients with common epithelial tumors of the ovary was investigated by means of endocrinological, histochemical, immune histochemical and autoradiographic techniques. Estrone and estradiol and their precursors were quantitatively extracted from the tumor tissue homogenate, and the results indicated that the estrogen-producing pathway was not uniform among the tumors. On the tissue section Sudan-IV staining showed positive in the stromal area in the form of fine granules or droplets. The immune peroxidase method revealed that the Sudan staining-positive substance included estrogen and its precursors. Estrogen was also detected in the epithelium, but it seemed to be present in the epithelial (tumor) cells as an estrogen-estrogen receptor complex. Cholesterol staining was focally positive in the subepithelial stromal area and incorporation of 3H-cholesterol into the stromal cells was observed by microautoradiography. These findings indicated that steroid synthesis from cholesterol to estrogen appeared in the stroma of the tumor and high serum concentrations of estrogen in the patient were the result of accelerated estrogen-synthesis in the ovarian tumor.

Autoradiography↗

[A case of vacuolated meningioma].

A rare case of falx meningioma with extensive vacuolization was reported. A 57-year-old woman was admitted to Okayama University Hospital because of numbness in her left lower limb. A plain CT scan showed a hypodense mass in the right frontal region with marked enhancement after contrast medium injection. MRI on T1 weighted images showed low intense mass with the so-called "peritumoral band" of low intensity at the periphery of the mass. Angiogram showed a mass effect and a tumor stain fed by the right pericallosal artery and left middle meningeal artery. The mass was excised en bloc. Microscopic examination demonstrated tumor cells with varied sized vacuoles, which were mostly fat-negative, except for small islands with typical meningothelial cells in the periphery of the tumor. Ultrastructurally, there were two kinds of vacuole in the tumor cells. The smaller, round vacuoles were in the cytoplasm, while the larger ones were in the extracellular space. The cell processes had developed junctional complex, and numerous cytoplasmic filaments were evident. With these findings, this mass was diagnosed as vacuolated meningioma. It is important especially in frozen section not to misdiagnose the tumor as liposarcoma, chordoma, metastatic brain tumor and so on.

Cerebral Angiography↗

[Immune parameters of peripheral blood in chemoembolization with microencapsulated anticancer drugs].

To investigate possible immunological consequences after arterial infusion of microencapsulated anticancer drug (chemoembolization), cellular immune parameters in peripheral blood were monitored for 4 weeks after chemoembolization in 20 patients with urological malignancies including 7 renal cell carcinomas, 2 renal pelvic carcinomas, 8 bladder carcinomas and 3 prostatic carcinomas. Natural killer (NK) cell activity and OKT4/8 ratio were augmented in 67% and 83% of the cases after chemoembolization respectively. Mature NK cell population (Leu7-OKT 16+) in these cases also showed a trend of continuous increase for more than 4 weeks. On the other hand, a small number of the patients showed an augmentation of OKT3+ cells, Ia-1+ cells or response to phytohemagglutinin. Histopathological examination of regional lymph nodes in 9 patients who underwent chemoembolization for renal cell carcinoma showed stimulating reactions in 8, while lymphocyte depletion in 1. These findings suggest that inhibition of micrometastasis by the enhanced natural killer cell activity could be anticipated in more than half of cases after chemoembolization.

Aged↗

[A case report of graft-versus-host reaction after aortocoronary bypass--a clinicopathological study].

An immunologically normal 70-year-old male developed fever and disturbance of consciousness after aortocoronary bypass; this was followed by diarrhea, systemic erythroderma and granulocytopenia. He died as a result of sepsis and acute renal failure. The skin biopsy showed basel vacuolar degeneration, epidermal eosinophilic necrosis and invasion of T-lymphocytes. The autopsy showed necrotic small interlobular bile ducts, severely hypoplastic bone marrow and widespread necrosis of lymphoid tissue. Based on these clinicopathological findings, we made a diagnosis of graft-versus host reaction after transfusion.

Aged↗

[Combined valvular and coronary artery surgery].

Combined valvular and coronary surgery were performed on 9 patients between 1973 and 1986. Valve replacements were consist of 5 AVR (including 1 translocated AVR and 1 Bentall operation), 2 MVR and 2 double valve replacement. Coronary surgery were of 6 aorto-coronary bypass using great saphenous veins, 1 innominate artery-coronary bypass using a Dacron prosthesis, 1 punch-out of coronary ostium and 1 dilatation of the left coronary ostium with a vein patch. Retrograde infusion of cardioplegic solution from the coronary sinus were done in patients with coronary ostial stenoses. One emergency case with acute cardiac failure died immediately after operation, and one with double valve and one with mitral valve replacement died of hepatic failure and multiple organ failure respectively within 1 year after surgery. Combined valvular and coronary surgery are necessary for patients with both diseases. Although the results of double valve replacement were not satisfactory, they would be improved using intra-aortic balloon pump and ventricular assist devices actively.

Adult↗

The subunit structure of a major glutathione S-transferase form, MT, in rat testis. Evidence for a heterodimer consisting of subunits with different isoelectric points.

A major glutathione S-transferase form (pI 5.7) in rat testis (MT) purified by S-hexyl-glutathione affinity chromatography, followed by chromatofocusing, showed two polypeptide of pI 6.7 (Yn1) and 6.0 (Yn2), having apparently the same molecular mass of 26 kDa on two-dimensional gel electrophoresis. Rechromatofocusing of the MT preparation after 4 M guanidine hydrochloride treatment revealed two additional protein peaks (pI 6.2 and 5.4). These were identified as the two homodimers consisting of the subunits of MT, Yn1Yn1 and Yn2Yn2, respectively. Furthermore, MT could be reconstituted from Yn1Yn1 and Yn2Yn2. These results indicate that MT is a heterodimer, Yn1Yn2, consisting of subunits with very similar molecular masses but different isoelectric points. The Yn1Yn1 form had glutathione S-transferase activities towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene. However, the Yn2Yn2 form had no activity towards any of the substrates examined. N-terminal amino acid sequences of subunits Yn1 and Yn2 revealed differences at two positions in the first 20 residues; the amino acid compositions of these subunits were also similar but not identical, indicating that these two subunits are different in the primary structure. Subunits Yn1 and Yn2 are immunologically related to each other and also to subunits 3 (Yb1) and 4 (Yb2) but they are not identical. These four subunits also showed a high degree of similarity in N-terminal amino acid sequences. Subunits Yn1 and Yn2 seem to belong to the rat GST 3-4 family or class mu. Subunits Yn1 and 4 can make a heterodimer, which is detectable not only in rat testis, but also in the heart, kidney and lung. The Yn1Yn1 form was not detected in the testis, but is present in rat brain [Tsuchida et al. (1987) Eur. J. Biochem. 170, 159-164]. The Yn2Yn2 form seemed to differ from GST 5-5 and may be a new form of rat glutathione S-transferase.

Amino Acid Sequence↗

Biochemical and immunological demonstration of prostaglandin D2, E2, and F2 alpha formation from prostaglandin H2 by various rat glutathione S-transferase isozymes.

Glutathione S-transferase isozymes purified from normal rat liver (1-1, 1-2, 2-2, 3-3, 3-4, and 4-4), liver with hyperplastic nodules (7-7), brain (Yn1Yn1), and testis (Yn1Yn2) all had prostaglandin H2-converting activity. The prostaglandin H2 E-isomerase activity was high in 1-1 (1400 nmol/min/mg protein), 1-2 (1170), and 2-2 (420), moderate in 3-3, 3-4, 4-4, Yn1Yn1, and Yn1Yn2 (52-100), and weak but significant in 7-7 (33). The prostaglandin H2 D-isomerase activity was relatively high in 1-1 (170) and 1-2 (200), moderate in 2-2 (60) and Yn1Yn2 (43), and weak but marked in 3-3 (16), 4-4 (16), and 7-7 (14). The prostaglandin H2 F-reductase activity was remarkable in 1-1 (1250), 1-2 (920), and 2-2 (390), and weakly detected in 3-3 (24), 4-4 (28), and 7-7 (14). Glutathione was absolutely required for these prostaglandin H2-converting reactions, and its stoichiometric consumption was associated with F-reductase activity but not E- and D-isomerase activities. The Km values for glutathione and prostaglandin H2 were about 200 and 10-40 microM, respectively. By immunoabsorption analyses with various antibodies specific for each isozyme, we examined its contribution to the formation of prostaglandins D2, E2, and F2 alpha from prostaglandin H2 in 100,000g supernatants of rat liver, kidney, and testis. In the liver, about 90% of the F-reductase activity (9.8 nmol/min/mg protein) was shown to be catalyzed by the 1-2 group of isozymes. The E-isomerase activity (16.5) was catalyzed about 60 and 40% by the 1-2 and 3-4 groups, respectively; and the D-isomerase activity (3.7) was catalyzed by the 1-2 group (50%) and the 3-4 group and Yn1Yn2 (15-25%). In the kidney, the E-isomerase activity (9.4) was catalyzed by 1-1, 1-2 (40%), 2-2, 3-4 group, and 7-7 (10-20%). The F-reductase activity (3.3) was mostly catalyzed by the 1-2 group (75%). In the testis, the E-isomerase activity (3.9) was catalyzed by the 1-2 group (20-30%), the 3-4 group, and Yn1Yn2 (30-60%).

Animals↗

Solubilization and partial purification of leukotriene C4 synthase from guinea-pig lung: a microsomal enzyme with high specificity towards 5,6-epoxide leukotriene A4.

Enzymic activities catalyzing allylic epoxide, leukotriene A4, to leukotriene C4 by conjugation with glutathione were present mainly in microsomal fractions of spleens and lungs of guinea pigs and rats. Leukotriene C4 (LTC4) synthase was solubilized from the microsomes of guinea-pig lung by the new procedures of a combination of 3-[3-cholamidopropyl)dimethylammonio)-1-propanesulfonate (CHAPS), digitonin and KCl. The enzyme was partially purified by two steps of column chromatography which resulted in a complete resolution of the enzyme from glutathione S-transferases (EC 2.5.1.18). The partially purified LTC4 synthase showed a Vmax value of 40 nmol/min per mg, and the apparent Km values for LTA4 and glutathione were 36 microM and 1.6 mM, respectively. The enzyme was unstable, and half of the activity was lost by incubation at 37 degrees C for 3 min. Glutathione at 10 mM completely protected the enzyme against this inactivation, while other sulfhydryl-group-reducing reagents were ineffective. The partially purified enzyme revealed a high specificity towards 5,6-epoxide leukotrienes (LTA4 and its methyl ester), while rat cytosolic glutathione S-transferases catalyzed conjugation of glutathione to various positional isomers of epoxide leukotrienes.

Animals↗

Pontine micturition center in the dog.

The function and location of the pontine micturition center was studied in ten decerebrate dogs by physiological experiments in which micturition induced by electrical stimulation of the pontine micturition center was compared with reflex micturition in response to bladder filling with physiological saline and by histological studies of the electrolytic lesions made at the stimulated areas. The micturition induced by electrical stimulation of the pontine micturition center showed the same pattern of detrusor contraction, simultaneous urethral relaxation and the elevation of the tail as reflex micturition in response to bladder filling. The peak contraction pressures in both micturitions showed no obvious differences. The electrolytic lesions were histologically identified at the locus coeruleus alpha in six out of 10 dogs, at the locus coeruleus in three and at the peri locus coeruleus alpha in one dog. The coordinated activities of bladder and urethra in the micturition induced by electrical stimulation of locus coeruleus or its subparts suggest that these areas perform an important role in the urine emptying function.

Animals↗

Ipsilaterality of motor innervation of canine urethral sphincter.

The functional activity of the sphincter muscle of the urethra is known to be controlled largely by the hypogastric and pudendal nerves. It remains unknown, however, whether innervation of the muscle by these peripheral nerves is ipsi- or bilateral. In an attempt to answer this question urethral closure pressure was determined simultaneously in the anterior, posterior, right and left portions of urethral wall in dogs. The pressure measurements were stereographed with the aid of a computer (stereo-UPP) and by this means the effect of unilateral section or electrical stimulation of hypogastric and pudendal nerves on the intraurethral pressure profile was analyzed. Unilateral section or electrical stimulation of the hypogastric nerve, distal to its division, produced a fall and a rise primarily in proximal intraurethral pressure, respectively, in all four directions. There was no significant difference in this response between the involved and uninvolved sides. Unilateral section of the pudendal nerve resulted in a fall primarily in distal intraurethral pressure in all four directions. No significant difference was present between the injured and noninjured sides. In contrast, electrical stimulation of the pudendal nerve distal to the point of its division caused a rise in intraurethral pressure in all four directions, with a significantly greater pressor response on the stimulated than on the nonstimulated side. These observations suggest decussating motor innervation of the urethra by the hypogastric nerves and also the possibility of the distal urethra being ipsilaterally innervated by the pudendal nerve.

Animals↗

Combination therapy with microwave coagulation and intracavitary irradiation for bladder cancer. Technique and preliminary clinical results.

Twenty-five patients with transitional cell carcinoma of the bladder have been treated with combined therapy consisting of microwave regional coagulation and intracavitary irradiation. A remote-controlled after-loading system was utilized for the radiation therapy. The follow-up period ranged from 6 to 19 months with an average of 11.4 months. Tumor stages were Tis (n = 2), Ta or T1 (n = 17), T2 (n = 2), T3 (n = 3) and T4 (n = 1), and grades were G1 (n = 10), G2 (n = 11) and G3 (n = 4). In 23 patients (92%), there was no endoscopic or histologic evidence of tumor after the initial treatment. Heterotopic recurrences were found after 2 or 3 months in 3 patients who received microwave regional coagulation or intracavitary regional irradiation. Additional intracavitary whole bladder mucosal irradiation was performed for 10 patients with multiple tumors and frequent recurrent tumors. Nine patients had no recurrence (average follow-up 11 months). Our preliminary findings indicate that combination therapy of microwave coagulation and intracavitary irradiation is a useful treatment for bladder cancer.

Brachytherapy↗

Microwave coagulation therapy for urinary bladder tumors.

A new device has been developed for microwave coagulation of urinary bladder tumors. Twenty-one patients with urinary bladder tumors were treated by irradiation with microwave energy of 2,450 MHz. Results were obtained as follows: (1) microwave coagulation was performed in 21 patients with transitional cell carcinoma of the urinary bladder. Excluding 4 patients who subsequently received radical cystectomy, 17 patients showed a complete response, although 2 patients subsequently developed recurrences in different parts of the bladder within the following several months. Histological examination of the excised specimen revealed complete eradication of the tumor in 2 patients. In the remaining 2 patients with high-stage tumor (T4), viable tumor cells were noted in the urethra or vaginal wall. (2) Although neither technical difficulties nor severe complications were encountered, transient urinary frequency and calcification of the bladder wall were noted. The results of this study indicate that microwave coagulation may be used in the treatment of both superficial and invasive tumors.

Aged↗