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Biomedical subjects

S Takeuchi

Publications and source records attributed to S Takeuchi.

At least 37 records · Page 2Linked to original sources

Angiogenesis in microvascular endothelial cells induced by glioma cells and inhibited by tumor necrosis factor in vitro.

Neovascularization is a prerequisite for glioma growth, so inhibition of angiogenesis may achieve control of glioma growth. We examined whether glioma cells induce angiogenesis and proliferation in microvascular endothelial cells from Fisher 344 rat brains by co-culture in a physical separation system with rat C6 glioma cells or rat T9 gliosarcoma cells. Endothelial cells cultured on type 1 collagen formed capillary-like structures. C6 glioma cells co-cultured with endothelial cells promoted the formation of these capillary-like structures. However, conditioned medium from C6 cells inhibited the proliferation of endothelial cells. T9 cells had little effect on the formation of capillary-like structures and no effect on the proliferation of endothelial cells. We also examined the effects of human tumor necrosis factor (TNF)-alpha on the formation of the capillary-like structures and on the proliferation of endothelial cells. Human TNF-alpha inhibited the formation of capillary-like structures induced by C6 glioma cells at a concentration of 100 U/ml, as well as the proliferation of endothelial cells at a concentration of 1000 U/ml. These results indicate that induction of angiogenesis varies with glioma cell lines and angiogenesis does not correspond with proliferation of endothelial cells. TNF-alpha can inhibit angiogenesis in gliomas in vitro.

Animals

Cochlear blood flow and labyrinthine pressure: effects of glycerol on the inner ear.

Changes in cochlear blood circulation (CoBC) and perilymphatic pressure (Pp) after administration of physiological saline and 50% glycerol (12 ml/kg) were measured simultaneously in guinea pigs to examine the influence of glycerol on CoBC and Pp. The CoBC was measured by the laser-Doppler method. Although neither CoBC nor Pp changed after administration of physiological saline, glycerol produced a marked increase in CoBC and a slight decrease in Pp in 11 of 15 animals. However, the increase in CoBC was transient; CoBC reached a peak as soon as 30 min after glycerol administration and then returned rapidly to its initial value within 1 h after administration, although the Pp was still decreasing. Therefore, the response of CoBC to glycerol does not seem to be directly related to hyperosmolarity due to glycerol administration.

Animals

Alterations of the p16 (MTS1) gene in testicular, ovarian, and endometrial malignancies.

PURPOSE: The p16 (MTS1) gene codes for a cyclin-dependent kinase inhibitor and may be a new tumor suppressor gene. It is frequently mutated in a variety of cell lines established from tumors. This is the first report of screening for alteration of the p16 gene in testicular, ovarian and endometrial malignancies. MATERIALS AND METHODS: We examined alterations of p16 in 78 primary genital tumors (42 testicular, 21 ovarian and 15 endometrial cancers) and mononuclear cells from 2 patients with Lynch syndrome II as well as 5 testicular tumor cell lines by single-strand conformation polymorphism (SSCP) and Southern blot hybridization. RESULTS: The DNA from the p16 gene of 2 testicular tumors (5%), an ovarian cancer (4%) and a testicular tumor cell line (20%) had altered migration in gel electrophoresis as shown by SSCP. Analysis of DNA sequence of these samples revealed a polymorphism at codon 140. Southern blot hybridization detected neither deletions nor rearrangements of the p16 gene in any of the samples. CONCLUSIONS: Taken together, these results suggest that p16 alterations probably are not important for tumorigenesis of testicular, ovarian and endometrial tumors.

Base Sequence

DNA aneuploidy in morphologically normal colons from patients with colon cancer.

DNA aneuploidy is common in colon carcinoma, colonic polyps, and ulcerative colitis. We found an interesting subset of patients with colon cancer. These individuals (14 of 230 cases, 6%) had hypodiploid aneuploidy in their morphologically normal-appearing colonic tissue. The aneuploid fractions were small, making up between 10 to 15% of the total events, and the ploidy pattern was not related to the ploidy pattern of the tumor. The clinical findings of the 14 patients were compared with those of patients who had diploid normal colons by age, location of the tumor, Dukes stage, and percent aneuploidy in the main tumor; the two groups were comparable. Both the normal colon and carcinomas of the 14 cases were studied by a newly developed "enriched" polymerase chain reaction for K-ras mutations. No K-ras mutations were found in the normal tissues, but mutations were found in the tumors of four cases. Cells from some colon cancers have a high degree of genetic instability, as shown by numerous mutations throughout the genome. Analysis of eight matched colon cancers and aneuploid, morphologically normal-appearing colons for genetic alterations, as measured by shifts in the electrophoretic mobility of microsatellite repeat fragments, showed that only one of eight colon cancer samples had microsatellite instability, which is the expected frequency. Taken together, the data suggest that individuals with colon cancer may have morphologically normal colonic tissue, which is genetically abnormal, and this abnormality may precede the development of mutations in K-ras.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

[The clinical usefulness of urinary determinations of cytokeratin 19 fragment (CYFRA 21-1) in urothelial tumor].

The urinary CYFRA 21-1 value corrected for urinary creatinine (ng/ml/creatinine), was studied in the urine of patients with urothelial tumors. To examine its clinical significance we studied urinary CYFRA 21-1 excretion (ng/ml/creatinine), in a total of 22 urine samples from patients with bladder cancer, 7 from patients with renal pelvic and ureteral tumor, 6 from patients with urinary infection 6 from patients with urinary diversion called ileal conduit, and 8 from healthy adult men. The excretion of CYFRA 21-1 in urine was determined by two specific monoclonal antibodies (Ks 19.1 and BW 19.21). The mean value of urinary CYFRA 21-1 in healthy adult men was 1.96 +/- 1.33 (mean +/- SD) ng/ml/creatinine. Urinary CYFRA 21-1 showed a higher value in the urine of urinary infection and urinary diversion. As to bladder cancer, urinary CYFRA 21-1 showed a higher value in a larger volume of tumor than in a smaller volume of tumor in transitional cell carcinoma regardless of the grade and stage. These findings suggest that urinary CYFRA 21-1 may be a non-specific marker in urothelial tumors.

Adult

[A case report of far advanced gastric cancer with multiple liver metastasis (H3) treated with transarterial intermittent chemotherapy and intradermal administration of low molecular lipopolysaccharide (LPSp) extracted from Pantoea agglomerans].

A case of far advanced gastric cancer with multiple liver metastasis (H3) was treated with transarterial intermittent chemotherapy (5-FU: 250 mg/week, Farmorubicin: 10 mg/4 weeks, MMC: 4 mg/2 weeks) and intradermal administration of low molecular lipopolysaccharide (LPSp) extracted from Pantoea agglomerans. The CT examination and endoscopy showed regression of the tumor and the patient was discharged from the hospital. LPSp was given at the concentration of 0.1 microgram initially, and the dose was gradually increased. Finally, the dose of LPSp was increased up to 70 micrograms. No serious side effect except fever was observed. The serum TNF-alpha levels were elevated and, histologically, CD 8(+) lymphocyte dominantly infiltrated around the tumor. These findings clearly indicated the immunological anticancer effect of LPSp. Intradermal administration of LPSp is a promising new adjuvant therapy to improve QOL without serious side effect.

Aged

Mutations of p53 in Wilms' tumors.

Mutations of p53 frequently occur in a wide variety of cancers including lung, breast, gastrointestinal, brain, and hematologic malignancies. These alterations apparently contributed to development of the malignant phenotype. Wilms' tumor is one of the most common solid tumors in childhood. The frequency of p53 alterations in this tumor is unknown. We analyzed 66 Wilms' tumor samples for p53 mutations by single-stand conformational polymorphism (SSCP) following polymerase chain reaction (PCR). Samples with an abnormal SSCP pattern were reamplified and analyzed by direct sequencing method. Mutations of p53 were found in three (5%) of 66 Wilms' tumors within the coding region (exons 2-11), showing that the frequency of p53 mutations was low. Two mutations substituted amino acids residues and one encoded a stop codon. Two of the mutations were located in the mutational hotspots (exons 5 and 6); the other was in exon 10. These data suggest that p53 mutations are infrequent in the development of Wilms' tumors.

Base Sequence

[A case of varicella pneumonia in an adult with moss-like substance in the bronchial mucosa].

A 33-year-old man complained of fever, cough and eruptions, and was admitted to our hospital. Chest X-ray films showed diffuse small nodular shadows. A moss-like substance in the bronchial mucosa was seen bronchoscopically. Transbronchial lung biopsy specimen showed infiltration of lymphocytes in the alveolar septa and peribronchiolar area. Transbronchial biopsy specimen of the bronchial lesion showed epithelial hyperplasia and necrosis. Immunohistochemical staining revealed VZV antigen.

Adult

[Extracorporeal shock wave lithotripsy on patients with spinal cord injury with special reference to autonomic hyperreflexia].

We performed treatment of urolithiasis on 7 patients with spinal cord injury (6 males and one female, with a mean age of 41 years old) by extracorporeal shock wave lithotripsy (ESWL) using a Lithostar (Siemens). The level of injury was cervical in 3 patients and lower thoracic in 4. The treated stones were renal in 6 patients, including one staghorn caliculus, ureteral in 2, and bladder stones in 2 patients. ESWL was performed under general anesthesia in 2 patients, and in another patient, epidural anaesthesia was employed in the first several sessions, but thereafter treatment was safely continued with no anesthesia. The other 4 patients were treated without anesthesia. In most patients, the stones (9 stones in 6 cases) were easily disintegrated after treatment of from one to 14 sessions, except one case of staghorn caliculus, and the clearance of fragments was also satisfactory. In one patient, hypertension and bradycardia due to autonomic hyperreflexia were observed during ESWL, and the treatment was discontinued, but the stone was successfully disintegrated and the fragments were voided. In another patient, autonomic hyperreflexia was observed while the fragments passed through the ureter, although no signs of this reflexia were seen during the ESWL procedure.

Adolescent

[A case of acquired von Willebrand disease due to pulmonary stenosis after Jatene's operation].

The case of a 9-year-old girl with pulmonary stenosis complicated by acquired bleeding tendency after Jatene's operation is reported. Coagulation study revealed that platelet count and von Willebrand factor were reduced. Catheterization study revealed severe pulmonary stenosis, the pressure gradient between the right ventricle (RV) and pulmonary artery (PA) being 190 mmHg. A link between pulmonary stenosis and bleeding tendency was suggested and the patient was diagnosed as having acquired von Willebrand disease due to activated platelet/von Willebrand factor interactions enhanced by "shear stress" at the site of pulmonary stenosis. Right ventricular outflow reconstruction was done when she was 9 years-old. Due to a protocol based on the results of the challenge test that we instituted to determine the efficacy and effective duration of blood derivatives and hemostatic agents, perioperative massive bleeding was avoided. Bleeding tendency disappeared and coagulation study findings normalized with correction of the abnormal hemodynamic state.

Child

[Extracorporeal shock wave lithotripsy monotherapy using Lithostar--factors influencing actuarial residual stone rates].

For the evaluation of post treatment course after initial extracorporeal shock wave lithotripsy (ESWL) as a monotherapy using the Lithostar, the actuarial residual stone rate (ARSR) was calculated by the Kaplan-Meier formula in 713 calculi (255 renal and 458 ureteral calculi). ARSRs in all calculi at 3, 6, 12 and 48 months were 41.6, 30.5, 20.6 and 10.3%, respectively. Significantly higher ARSRs were observed in the following former group compared to the latter: large calculi to small or middle sized calculi, renal calculi to ureteral calculi (small or middle sized), and plural renal calculi (middle sized) to single renal calculi (middle sized). There was no significant difference either between large renal and large ureteral calculi, or overall single and plural calculi. These findings show that ARSRs calculated by the Kaplan-Meier formula clearly reveal factors influencing the ESWL effects.

Follow-Up Studies

[Study on prevention of flare-up phenomenon following initial LH-RH analogue administration: combination therapy with diethylstilbestrol].

To eliminate the initial testosterone (T) surge and prevent the risk of flare-up induced by the first administration of luteinizing hormone-releasing hormone (LH-RH) analogue, we examined the effectiveness of short-term combination therapy with diethylstilbestrol (DES). Sixteen previously untreated patients with prostate carcinoma (Stage C: 4 cases, Stage D2: 12 cases) were randomly assigned to 4 groups. Each group included 4 patients. Group 1 received DES (500 mg daily injection) for 7 days, staring before the first subcutaneous injection of luteinizing hormone releasing hormone (LH-RH) analogue (3.6 mg of Zoladex depot); Group 2 received 500 mg of DES injection for 7 days prior to the initiation of therapy with the LH-RH analogue, and moreover received a DES injection for 7 days; Group 3 received 500 mg of DES injection for 7 days simultaneously with the first injection of the LH-RH analogue; Group 4 was pretreated with 500 mg of DES injection for 7 days prior to the initiation of therapy with the LH-RH analogue, with additional DES injection for 3 days. In groups 1, 2 and 4 the level of T decreased during the 7 days of DES therapy, and at 3 days after the first injection of LH-RH analogue increased again. The mean T value in groups 1, 2 and 4 decreased by 33.2 +/- 27.6% (mean +/- SE), 20.5 +/- 20.8%, 13.2 +/- 9.8%, respectively, at the day of the first injection of LH-RH analogue, and increased by 75.2 +/- 21.6%, 70.7 +/- 63.4%, 56.7 +/- 46.4%, respectively, at 3 days after the first injection of LH-RH analogue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

Absence of WAF1 mutations in a variety of human malignancies.

A newly cloned gene named wild-type p53-activated fragment 1 (WAF1; also known as p21, Pic-1, Cip-1, or SDI1) is directly regulated by p53 and can itself suppress tumor cell growth in culture. Induction of expression of WAF1 may be an important means by which cells with DNA injury arrest their growth to repair DNA or undergo apoptosis. Based on the hypothesis that mutations of this gene may play a role in carcinogenesis, we have studied 351 DNAs from 14 kinds of malignancies, as well as 36 human transformed cell lines, for alterations of WAF1 gene by single-strand conformation polymorphism analysis of polymerase chain reaction amplification of the DNA coding region of the WAF1 gene. No abnormal band shifts of WAF1 were noted in any of the samples or cell lines, but three major variants in exons 2 and 3 of the gene were found that are consistent with the existence of two different DNA polymorphisms. Sequence analysis of the amplified products producing these three variants in each exon from normal DNAs confirmed the presence of the polymorphisms in the WAF1 gene. Of 290 selected tumor samples previously evaluated for p53 mutations by single-strand conformation polymorphism, 90% had no detectable p53 alterations. In summary, mutations within the coding portion of the WAF1 gene were undetectable in a large series of human tumors, many of which had a normal p53 gene. This suggests that WAF1 alterations are generally caused indirectly, through p53 mutations rather than through intragenic mutation of the WAF1 itself.

Base Sequence

Effect of menthol on cytosolic Ca2+ levels in canine airway epithelium in culture.

Intracellular Ca2+ concentration ([Ca2+]i) in canine cultured tracheal epithelium in response to cyclic alcohols was measured by a fura-2 method. Menthol rapidly increased [Ca2+]i in a concentration-dependent fashion, the maximal increase from the baseline levels and the concentration of menthol required to produce a half-maximal effect (EC50) being 148 +/- 23 nM (mean +/- SE, p < 0.001) and 0.3 mM, respectively, whereas other cyclic alcohols including menthone and cyclohexanol had no effect. The menthol-induced increase in [Ca2+]i was not affected by verapamil but partially inhibited by low Ca2+ medium in the presence of EGTA. These results indicate that menthol specifically increases cytosolic Ca2+ in airway epithelium, which may be derived from intracellular Ca2+ stores.

Animals

Epidermal growth factor receptor content in human renal cell carcinomas.

BACKGROUND: The expression of epidermal growth factor receptor (EGFR) mRNA has been demonstrated in human renal cell carcinomas (RCC), but few reports quantitate EGFR in RCC and correlate EGFR content with clinicopathologic findings. METHODS: Using 125I-EGF as a ligand, the maximum binding of EGF in membrane preparations from RCC (EGFR content) was studied by Scatchard analysis. RESULTS: A single class of binding sites for EGF was observed in 74% of RCC and 50% of normal renal tissues. The EGFR content was increased significantly in RCC compared with normal tissues. In all cases in which EGFR was undetectable, there was no evidence of distant metastasis, venous invasion, or regional lymph node involvement, and these patients had a better clinical outcome than patients with detectable EGFR. The EGFR content was significantly lower in nuclear Grade 1 tumors than in tumors of higher nuclear grades. No significant difference between EGFR content and other clinicopathologic findings was detected. CONCLUSION: The determination of EGFR content in RCC may become an important prognostic factor for the biologic behavior of RCC.

Adult

Clival chordoma in early childhood without bone involvement.

Intracranial chordomas are rare in childhood. Only 15 cases have been reported in children less than 6 years old. Bone destruction and calcification have been stated to be characteristics of this tumor. We present the case of a 5-year-old boy with clival chordoma without bone involvement.

Brain Neoplasms

Cerebral haemodynamic changes after endovascular treatment of arteriovenous malformations: evaluation by single-photon emission CT.

Cerebral haemodynamic changes in 17 patients with cerebral arteriovenous malformations (AVMs), who showed hypoperfusion on single-photon emission computed tomography (SPECT) before endovascular treatment, were studied after embolization. Nine of them had non-haemorrhagic clinical manifestations and the other eight had a history of intracranial haemorrhage. Obliteration of AVMs was nearly total in six patients and partial in eleven. New low density lesions on X-ray computed tomography (CT) developed in 3 of 6 patients after nearly total obliteration and one of 11 patients after partial obliteration. The first SPECT after embolization showed diminished hypoperfusion in 11 of 13 patients without new low density lesions and one of 4 patients with new low density lesions. Diminution of hypoperfusion was seen even in two patients who underwent SPECT study immediately after the embolization. Cerebral circulation was improved in five of eight patients with low density lesions before embolization and in nine of eleven patients after partial obliteration. Hypoperfused state in the haemorrhagic group tended to remain unchanged compared with that in the non-haemorrhagic group. The hypoperfused area was expanded after embolization in three patients with new cerebral infarction. It is important for improvement of cerebral circulation to reduce the shunt flow without causing new infarction due to the embolization itself. In one of two patients who had a hyperperfused area surrounding the AVM after embolization, an unexpected and abnormal degree of brain swelling and haemorrhage occurred at the end of the surgery 20 days after the embolization. In the other patient, total extirpation was successfully performed after confirming disappearance of hyperperfusion in the follow-up SPECT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Uterine myxoid leiomyosarcoma and CYVADIC-etoposide therapy.

OBJECTIVES: To conduct a pathological characterization of rare uterine myxoid leiomyosarcoma (MLS) and establish an effective chemotherapy for metastasis after hysterectomy. METHODS: Histological and immunohistochemical methods were used to characterize the type of uterine MLS in a 39-year-old female. For multiple lung metastases found 3 months after operation, CYVADIC (400 mg cyclophosphamide, 1 mg vincristine, 50 mg epirubicin and 400 mg dacarbazine per body for one course) and oral etoposide (50 mg/body per day for 2 weeks) were applied. RESULTS: The rapidly enlarging uterine tumors exhibited gelatinous cut surfaces, a high count of 30 mitotic cells per 10 hpf and mucinous stroma, indicating a rare high-mitotic type of uterine MLS. The two-course CYVADIC-etoposide therapy was effective for disseminated pulmonary metastases. CONCLUSION: The present MLS was a rare high-mitotic type. CYVADIC-etoposide was an optional effective chemotherapy for lung metastasis in this case.

Adult