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Biomedical subjects

S Takeuchi

Publications and source records attributed to S Takeuchi.

At least 55 records · Page 3Linked to original sources

[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

Immortalization of plasma cells by plasmid DNA and its hybridoma.

Human plasma cell lines producing IgG were cloned by the limiting dilution method from polyclonally immortalized B-cell lines with the plasmid DNA (pSVTLbsr) containing simian virus 40 (SV40)-gene from primary peripheral blood mononuclear cells of healthy and nonimmune volunteers. The plasma cell lines fused well with conventional partner cells and became evenly IgG-producing hybridomas at high efficiency, especially with the partner cell from human origin. One of the difficulties in obtaining stable IgG-producing hybridoma using Epstein-Barr virus (EBV) transformation followed by back fusion with partner cells, might mainly be attributed to the inability to immortalize plasma cells on account of the very low density of CD21 (EBV receptor) on the cell surface. The present CD21-independent immortalization by plasmid DNA and by the infection with SV40 protein-coated plasmid DNA will be a potentially effective method to obtain IgG-producing human monoclonal antibodies.

Adult

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

Leiomyoblastoma causing acute gastric outlet obstruction in an infant.

A 1-year-old boy had acute gastric outlet obstruction, the cause of which was a prepyloric submucosal mass. The mass and the ulcerated overlying mucosa were excised. The histological diagnosis was leiomyoblastoma with parenchymatous hemorrhage. Apparently, he is the youngest patient reported to have this disease.

Acute Disease

Thapsigargin, a Ca(2+)-ATPase inhibitor, relaxes rat aorta via nitric oxide formation.

Thapsigargin induced endothelium-dependent relaxation and cGMP production in rat thoracic aorta, and these effects were inhibited by nitric oxide (NO) pathway inhibitors, a calmodulin inhibitor and removal of Ca2+, suggesting that NO is involved in the thapsigargin-induced relaxation. Thapsigargin may deplete Ca2+ stores in the endothelial cells by inhibiting the Ca(2+)-ATPase, a Ca2+ pump, which in turn triggers influx of extracellular Ca2+, leading to activation of constitutive NO synthase and resultant NO generation. The NO thus formed may activate soluble guanylate cyclase to produce cGMP in the vascular smooth muscle.

Aminoquinolines

Sleep-related changes in human muscle and skin sympathetic nerve activities.

To characterize the features of sympathetic nerve activity during non-REM sleep, we measured the muscle and skin sympathetic nerve activities (MSNA and SSNA, respectively) using a double recording microneurographic technique. Eight healthy volunteers were monitored by polysomnography (including EEG, EOG, EMG, and ECG) and received acoustic stimuli (880 Hz, 125 ms) during sleep stage 2. The specific discharge properties of MSNA during wakefulness included pulse-synchronicity, short burst duration and a non-responsiveness to arousal stimuli. These were considered to be generated by an inhibitory input from the baroreceptors to the cardiovascular center. In contrast, SSNA lacked pulse-synchronicity, had longer bursts, and was responsive to a variety of stimuli. Burst rates of MSNA and SSNA were reduced during sleep stages 1 and 2 (light sleep) vs. during a wakefulness. Both MSNA and SSNA appeared to be related to spontaneously occurring K-complexes. The baroreflex latency (from the ECG R-wave to the integrated MSNA burst peak) was constant at approximately 1.20 s during sleep, suggesting that pulse-synchronicity was maintained. The MSNA burst evolution time (interval between initiation of the burst and its peak) became longer with a transition to deeper non-REM sleep stages, whereas the SSNA burst evolution times remained constant. K-complexes induced by acoustic stimuli were frequently accompanied by MSNA and/or SSNA. MSNA responded to acoustic stimuli during light sleep, but some bursts lacked a close relation in time to cardiac rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation

Inhibition of human immunodeficiency virus type 1 (HIV-1) replication by daphnodorins.

Three flavans, daphnodorins A, B and C isolated from Dahpne odora THUNB. were tested for their abilities to inhibit human immunodeficiency virus type 1 (HIV-1(IIIB)) replication in MT-4 cells. The effective concentrations (EC50) of daphnodorins A, B and C against HIV-1-induced cytolysis were 0.26 +/- 0.08, 1.8 +/- 0.6 and 3.6 +/- 0.5 micrograms/ml, respectively. Also these three compounds showed inhibitory effects of p24 antigen in human peripheral blood lymphocytes. As compared with 2',3'-dideoxycytidine 5'-triphosphate (DDC-TP), daphnodorin A and daphnodorin C had relatively weak inhibitory effects on the reverse transcriptase of HIV-1, while daphnodorin B did not show any inhibitory effect at concentrations up to 1000 micrograms/ml. These three compounds showed marked inhibitory effects on syncytium formation between HIV-1(IIIB)-infected and uninfected MOLT-4 (clone 8) cells at 3-30 micrograms/ml without inducing cytotoxicity. The concentrations of the compounds blocking syncytium formation were consistent with the effective concentrations (EC50) against HIV-induced cytolysis of MT-4 cells. These results, differing from reverse transcriptase inhibitors, suggest that the daphnodorins exert their anti-HIV-1 activity through inhibition of early events of viral replication including adsorption of the virions to the cells or the subsequent entry.

Antiviral Agents

Autologous blood transfusion using recombinant human erythropoietin in radical hysterectomy.

The possibility of serious complications of infection and GVHD and adverse prognosis in cancer patients resulting from homologous blood transfusions has been reported. We used recombinant human erythropoietin (rHuEPO) in autologous blood transfusions for radical hysterectomies to avoid the risks associated with transfusions. rHuEPO efficacy, stability and influence on hemodynamics were investigated. All patients were able to donate 1,200 ml of autologous blood prior to surgery, and anemia did not result despite phlebotomy three times each week. Elevation in Hb concentration was calculated at 0.78 +/- 0.37 g/dl over the first 7 days, and 2.12 +/- 0.35 g/dl over the first 14 days. No adverse side effects were observed in any patient. The serum EPO level was measured by RIA, and compared to the homologous blood transfusion group. rHuEPO did not influence postoperative EPO secretion. Autologous blood transfusion with rHuEPO in radical hysterectomy was extremely effective in mitigating the risks associated with homologous blood transfusions.

Blood Transfusion, Autologous

Effect of relaxation training on cardiac parasympathetic tone.

To examine the hypothesis that the relaxation response is associated with an increase in cardiac parasympathetic tone, the frequency components of heart rate variability during relaxation training were investigated in 16 college students. Electrocardiograms and pneumograms were recorded during a 5-min baseline period followed by three successive 5-min sessions of the autogenic training (relaxation) or by the same periods of quiet rest (control), while subjects breathed synchronously with a visual pacemaker (0.25 Hz). Although neither the magnitude nor the frequency of respiration showed a significant difference between relaxation and control, the amplitude of the high-frequency component of heart rate variability increased only during relaxation (p = .008). There was no significant difference in the ratio of the low-frequency (0.04-0.15 Hz) to the high-frequency amplitudes. The increased high-frequency amplitude without changes in the respiratory parameters indicates enhanced cardiac parasympathetic tone. Thus, our results support the initial hypothesis of this study. Enhanced cardiac parasympathetic tone may explain an important mechanism underlying the beneficial effect of the relaxation response.

Adult

Stimulation by menthol of Cl secretion via a Ca(2+)-dependent mechanism in canine airway epithelium.

1. To investigate the effect of menthol on airway epithelial ion transport function, we studied the bioelectrical properties of canine cultured tracheal epithelium by Ussing's short-circuit technique in vitro. 2. Addition of menthol (10(-3) M) to the mucosal but not the submucosal solution increased the short-circuit current (Isc) from 6.2 +/- 0.9 to 14.0 +/- 2.2 microA cm-2 (P < 0.001), and this effect was accompanied by increases in transepithelial potential difference and conductance. The response was dose-dependent, with the maximal increase from the baseline value and the concentration required to produce a half-maximal effect (EC50) being 6.4 +/- 0.9 microA cm-2 (P < 0.001) and 40 microM, respectively. 3. Other cyclic alcohols, including menthone and cyclohexanol, had no effect on the electrical properties. 4. The menthol-induced increase in Isc was not altered by pretreatment of the cells with amiloride, indomethacin, or propranolol but was abolished by diphenylamine-2-carboxylate, furosemide or substitution of Cl with iodide in the medium. 5. Menthol (10(-3) M) increased cytosolic levels of free calcium ([Ca2+]i) from 98 +/- 12 to 340 +/- 49 nM (P < 0.01) in fura-2-loaded tracheal epithelium but did not affect the intracellular adenosine 3',5'-cyclic monophosphate content. 6. These results suggest that menthol stimulates Cl secretion across airway epithelium, probably through a Ca(2+)-dependent mechanism, and might thus influence mucociliary transport in the respiratory tract.

Animals

Relaxation of rat thoracic aorta induced by the Ca(2+)-ATPase inhibitor, cyclopiazonic acid, possibly through nitric oxide formation.

1 The effect of the Ca(2+)-ATPase inhibitor, cyclopiazonic acid (CPA), was studied on rat thoracic aortic ring preparations. 2 At concentrations above 0.3 microM, CPA induced relaxation in the arteries precontracted with phenylephrine. Removal of the endothelium abolished CPA-induced relaxation. 3 The nitric oxide (NO) synthase inhibitor NG-nitro L-arginine (3-300 microM), the free radical scavenger haemoglobin (0.1-3 microM), the soluble guanylate cyclase inhibitor, LY83583 (0.1-10 microM), each inhibited the endothelium-dependent relaxation to CPA. The potassium channel blocker, glibenclamide (10 microM) and cyclo-oxygenase inhibitor, indomethacin (100 microM for 60 min and then washed out) did not alter the action of CPA. 4 The calmodulin inhibitors calmidazolium (3-10 microM) and W-7 (100 microM) also abolished CPA-induced relaxation. 5 CPA (10 microM) increased guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in arteries with an intact endothelium, without affecting adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels. 6 The inhibitors of NO synthesis and actions, the calmodulin inhibitor and removal of the endothelium abolished the CPA-stimulated increase in the levels of cyclic GMP. 7 In Ca(2+)-free solution, CPA failed to induce relaxation or to stimulate cyclic GMP production. Relaxation to nitroprusside was not affected under these conditions. 8 These results suggest that CPA can stimulate NO synthesis, possibly by inhibiting a Ca(2+)-ATPase, which replenishes Ca2+ in the intracellular storage sites in endothelial cells. Depletion of the Ca2+ store in the endothelium may then trigger influx of extracellular Ca2+, contributing to an increase in free Ca2+ in the endothelial cells, which activates NO synthase and NO formation.

Amino Acid Oxidoreductases

[Suppression of the Pseudomonas aeruginosa-induced biofilm formation on human epithelial cells by erythromycin].

In the present study, were examined the inhibitory effect of erythromycin on the biofilm formation by a temperature-sensitive mutant (Ts25) of Pseudomonas aeruginosa N-42 on the surface of Ishikawa cells which can produce a mucin-like glycoprotein physicochemically similar to mucoproteins produced in the human airway. Usually, 38-45 microcolonies (biofilms) were formed after 10 days of incubation in cultures of Ishikawa cells and P. aeruginosa Ts25. Erythromcin suppressed the adhesion to Ishikawsa cells of P. aeruginosa and its subsequent biofilm formation at doses as low as 0.2 microgram/ml. Erythromycin also exhibited the suppressive effect on the production of glycoproteins by Ishikawa cells at doses higher than 1 microgram/ml and the production of elastase and exoenxyme A from P. aeruginosa at doses higher than 2 micrograms/ml. These results suggest that erythromycin can inhibit the biofilm formation in culture of human epithelial cells and P. aeruginosa and the in-vivo bacterial biofilm formation may be attributed to host cell-derived factors rather than bacterial products.

Biofilms

[An evaluation of pathogens in patients with bronchopulmonary infection by transtracheal aspiration: December 1978-March 1993].

We performed transtracheal aspiration (TTA) in 1165 patients, who were suspected to have bronchopulmonary infection, from December 1978 to March 1993. We isolated pathogens from TTA in 806 patients (69.2%). We isolated H. influenzae (62 cases), S. pneumoniae (39 cases) and M. catarrhalis (24 cases) in patients with acute bronchitis, S. pneumoniae (65 cases), alpha-Streptococcus sp. (52 cases), H. influenzae (32 cases) and S. aureus (29 cases) in patients with pneumonia or lung abscess and H. influenzae (174 cases), S. pneumoniae (84 cases), P. aeruginosa (81 cases) and M. catarrhalis (42 cases) in patients with chronic lower respiratory tract infection. Anaerobic bacteria isolated from TTA included Peptostreptococcus sp. (19 cases), Bacteroides sp. (19 cases) and others. Mycoplasma pneumoniae was isolated from TTA in 8 patients with pneumonia without other organisms. Virus isolated from TTA included Rhinovirus (6 cases) and others. These results suggest that various pathogens affect the pathogenesis of bronchopulmonary infection. Therefore, we must diagnose the bronchopulmonary infection by the correct methods such as TTA.

Adult