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Biomedical subjects

T Machida

Publications and source records attributed to T Machida.

At least 37 records · Page 2Linked to original sources
PubMed1998

Newly synthesized dihydropyridine derivatives as modulators of P-glycoprotein-mediated multidrug resistance.

Newly synthesized 1,4-dihydropyridine derivatives possessing alkyl chains at the 4-position screened whether they could overcome P-glycoprotein-mediated multidrug resistance in cultured cancer cells and also leukemia-bearing animals. Of these derivatives, some could overcome drug resistance to doxorubicin and vincristine in multidrug resistant human cancer cell lines. Combined administration of vincristine and some of the derivatives significantly increased the life span of P-glycoprotein overexpressing multidrug-resistant P388 leukemia-bearing mice. The calcium antagonistic activities, an undesirable effects, were weaker than that of verapamil. These results suggested that the introduction of alkyl groups at the 4-position were effective for both overcoming multidrug resistance and reducing the calcium antagonistic activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Bropirimine, an orally active anticancer agent for superficial bladder cancer.

OBJECTIVE: To investigate efficacy and safety of bropirimine, a new orally active interferon inducer, in patients with superficial bladder cancer. METHODS: Twenty patients with histologically confirmed recurrent superficial transitional cell carcinoma (Ta or T1) were studied. At least one marker lesion remained in all patients after transurethral resection. Bropirimine (750 mg) was given orally three times at 2-hour intervals (daily dose 2,250 mg) on 3 consecutive days weekly for 12 weeks. RESULTS: Of the 17 evaluable patients, 1 did not complete the treatment protocol. There were 5 responders, including 2 with a complete response (complete disappearance of the marker tumor) and 3 with a partial response (>50% reduction of the marker tumor). The objective response rate was 31.3% (5/16; 95% confidence interval 11.0-58.7%) for the 16 patients completing treatment and 29.4% (5/17; 95% confidence interval 10.3-56.0%) for the 17 evaluable patients. Adverse reactions occurred in 70.6% of the evaluable patients. Flu-like symptoms were most common, including malaise (23.5%), headache (23.5), and fever (11.8%), followed by gastrointestinal symptoms including less of appetite (23.5%). All of these reactions were tolerable. CONCLUSIONS: Bropirimine may be useful for the prophylaxis of recurrence following transurethral resection of superficial bladder cancer because it shows efficacy against marker tumors and has a good safety profile and oral activity.

Administration, Oral↗
PubMed1998

Development of novel reversal agents, imidazothiazole derivatives, targeting MDR1- and MRP-mediated multidrug resistance.

Three newly synthesized imidazothiazole derivatives (N276-12, N276-14, N276-17) were examined regarding their ability and mechanism as a chemosensitizing agent against multidrug resistance 1 (MDR1)-mediated and multidrug resistance-associated protein (MRP)-mediated MDR. All three N276 compounds almost completely reversed the acquired resistance to vincristine (VCR), vinblastine (VBL), and doxorubicin (DXR) in MDR1-overexpressing human cancer cell lines (KB/VJ300 and T24/VCR). Their reversal effect against acquired resistance to VCR, DXR, and etoposide (VP16) was partial but clearly observed in the cell line expressing MRP (KB/VP4). All three N276 compounds enhanced the intracellular accumulation of [3H]VCR in MDR1-overexpressing KB/VJ300 cells through the inhibition of the increased efflux of the drug. They (100 microM) almost completely inhibited the photoaffinity labeling of P-glycoprotein encoded by the MDR1 gene. All the N276 compounds also remarkably enhanced the sensitivity to VBL and DXR in both MDR1- and MRP-overexpressing renal cell carcinoma (RCC) cell line (NKK1), whereas they showed no potentiation of these anticancer agents in an RCC cell line (KPK1) expressing neither MDR1 nor MRP. The combination chemotherapy of VCR or VP16 with N276-12 significantly increased the life span of mice inoculated i.p. or i.v. with drug-resistant P388/VCR cells without any significant side effects, whereas chemotherapy with the anticancer agent alone did not increase the life span at all. These results suggest that these newly synthesized imidazothiazole derivatives can be a useful chemosensitizing agent against not only MDR1- but also MRP-mediated MDR.

ATP-Binding Cassette Transporters↗
PubMed1997

MAP kinase links the fertilization signal transduction pathway to the G1/S-phase transition in starfish eggs.

The mechanism by which fertilization initiates S-phase in the zygote is examined by manipulating the activity of MAP kinase in mature starfish eggs. These unfertilized eggs, which are arrested at G1-phase after the completion of meiosis, have high MAP kinase activity but undetectable cdc2 kinase activity. Either fertilization or inhibition of protein synthesis causes a decrease in MAP kinase activity, which is followed by DNA synthesis. Inactivation of MAP kinase with its specific phosphatase, CL100, initiates DNA synthesis in the absence of fertilization, while constitutive activation of MAP kinase with MEK represses the initiation of DNA synthesis following fertilization. Thus, in unfertilized mature starfish eggs, a capacity for DNA replication is already acquired, but entry into S-phase is negatively regulated by MAP kinase activity that is supported by a continuously synthesized protein(s) but not by cdc2 kinase. Upon fertilization, downregulation of MAP kinase activity is necessary and sufficient for triggering the G1/S-phase transition.

Adenine↗
PubMed1997

Prolactin secretion in endometriotic patients.

OBJECTIVE: To clarify a significance of prolactin (PRL) for infertility in endometriosis. STUDY DESIGNS: For seventy endometriotic patients with or without infertility, serum PRL concentrations measured by radioimmunoassay before and 30 min after 500 micrograms of thyrotropin-releasing hormone (TRH) injection were analyzed in relation to the Revised American Fertility Society score in endometriosis as well as to the outcome of the treatment for endometriotic infertility. RESULTS: While no significant relationship was found between the basal PRL levels and the stage of endometriosis or the outcome of the treatment for infertility, the PRL value after TRH injection was significantly greater in the patients who did not become pregnant than those who did (P < 0.05). CONCLUSIONS: Occult hyperprolactinemia may be involved in infertility in endometriotic patients.

Adolescent↗
PubMed1997

[Bropirimine (U-54461S) early phase II clinical studies--to investigate the efficacy and safety of bropirimine treatment on various malignant tumors (urological, hematologic, and dermal cancers)].

Early Phase II clinical studies with bropirimine (U-54461S) having interferon (IFN) inducing and direct antiproliferative activities were conducted in patients with various solid tumors or hematologic neoplasm at 34 institutions nationwide. To investigate the safety and efficacy of the treatment, bropirimine was orally administered to the patients at the dose of 1g every two hours, three times a day for three consecutive days with a four day drug-free interval. Among the 65 patients registered, 60 patients were eligible and 44 patients completed bropirimine treatment in accordance with the respective protocols. Complete response (CR) was observed in 7 cases, and partial response (PR) was observed in 4 cases, so the efficacy rate was 25.0% (7 CRs + 4 PRs/44). Classified by target tumors, the efficacy rates were 12.9% (6 CRs/14) in bladder CIS, 33.3% 1 CR/3) in superficial bladder cancer. 11.1% 1 PR/9) in renal cell carcinoma, and 42.9% (3 PRs/7) in malignant lymphoma, respectively. Adverse drug reactions frequently observed were influenza-like symptoms such as fever (60.0%) and generalized malaise (21.7%), gastrointestinal symptoms like anorexia (56.7%) and nausea/vomiting (43.3%), and adverse effects on the circulatory system such as tachycardia (15.0%) and abnormalities in ECG (11.7%). Most of these symptoms were relieved or improved. Abnormalities in laboratory tests observed frequently were adverse effects on the liver such as elevations in GPT (33.3%), in GOT (31.7%), and in LDH (18.3%) or on the blood system like a decrease in RBC (18.3%), leukopenia (26.7%), or neutropenia (25.0%). In conclusion, bropirimine treatment proved to be effective for bladder CIS in particular, suggesting that it will be promising for use in the treatment of the disease.

Adult↗
PubMed1997

[Bropirimine (U-54461S) late phase II clinical study for carcinoma in situ of the bladder. Japan Bropirimine Study Group].

Late Phase II clinical study with bropirimine (U-54461S), a novel oral antitumor agent that has interferon inducing and anti-proliferative activities, was conducted in patients with bladder CIS at 38 institutions nationwide. To investigate the efficacy and safety of the treatment, bropirimine was administered to the patients at the dose of 750 mg every two hours, three times a day, for three consecutive days with four-day drug withdrawal, based on the results of the preceding clinical studies up to early phase II. Among the 48 patients registered, 41 patients were evaluable for antitumor efficacy. Complete response (CR) was observed in 17 of them, no change (NC) in 18 patients, and progressive disease (PD) in 6 patients; so the efficacy rate was 41.5%. Classified by patient background, the efficacy rates were 58.3% (7/12) in patients with primary bladder CIS, 34.5% (10/29) in those with secondary bladder CIS, 45.5% (10/22) in those with Grade 3, and 23.8% (5/21) in those previously given chemotherapeutic agents or BCG by intravesical or other routes. Adverse drug reactions frequently observed were influenza-like symptoms such as fever and generalized malaise and gastrointestinal symptoms like anorexia and nausea/vomiting; these symptoms were all Grade 2 or milder. Abnormalities in laboratory tests, such as an elevation in GOT/GPT, neutropenia, and leukopenia were observed. These adverse effects were all tolerated by the patients. From the above results, bropirimine was considered to be a useful oral agent for the treatment of bladder CIS.

Administration, Oral↗
PubMed1997

[Malignant mesothelioma of the tunica vaginalis: a case report].

An 18-year-old man visited our hospital with a painless swelling of the left scrotal contents. Transscrotal ultrasonography revealed a hydrocele and a 10-mm nodular mass attached to the tunica vaginalis. Tumor resection and hydrocelectomy were performed because the intra-operative histological diagnosis of a frozen section did not reveal malignancy. However, since the postoperative pathological diagnosis was malignant mesothelioma, the left hemiscrotum was excised. He has been free of disease 15 months postoperatively.

Adolescent↗
PubMed1997

[Giant testicular tumor associated with scrotal gangrene: a case report].

A case of giant testicular tumor associated with scrotal gangrene is reported. A 33-year-old man had a swollen scrotum (15 cm) accompanied with necrosis and a foulodor. The tumor had invaded the scrotum, perineum and the left spermatic cord. Serum alpha-fetoprotein level was 15,487 ng/ml. The chest radiograph revealed multiple metastases. Bilateral high orchiectomies and local resection with a wide margin were performed. The tumor weighed 2.5 kg and the histopathological diagnosis was teratocarcinoma. He was treated with 3 courses of chemotherapy with cisplatin, etoposide and peplomycin. A second-look surgery revealed no viable cancer cells in the residual masses. The patient has been free of recurrence 4 months postoperatively.

Adult↗
PubMed1997

[A case of sarcoidosis with proliferative retinopathy].

A 19-year-old female manifested severe bilateral panuveitis with neovascularization in the iris, optic disc, and retina. Fluorescein fundus angiography showed dye leakage from the optic disc and retinal blood vessels, and a large non-perfused area was present in the peripheral retina of the right eye. Sarcoidosis was diagnosed histologically by conjunctival and skin biopsy. Although the patient was given a large dose of a corticosteroid systemically and received panretinal photocoagulation, a dense vitreous hemorrhage and cataract were apparent in the right eye. The right visual acuity decreased to hand motions. A pars plana lensectomy and vitrectomy were performed. After vitrectomy, inflammation and neovascularization regressed and the visual acuity improved to 20/100. Proliferative membrane obtained during vitrectomy was histopathologically studied by light and electron microscopy. Many new vessels containing neutrophils were observed. A direct effect of inflammation as well as ischemia in the retina may have been the stimulus for the proliferative changes.

Adult↗
PubMed1997

[An surgical case of right pulmonary coccidioidomycosis--with subcutaneous coccidiomycosis in the left wrist].

Coccidioides is an afferent fungus disease. In Japan, there have been only a few surgical reports on coccidioides disease. We report a 39-year-old male who was diagnosed as having coccidioides disease by biopsy of subcutaneous nodules in the left wrist. The patient also showed a tumor image (1.5 x 1.0 cm) in S4 in the right lung. He had previously lived in Fresno, California on business between 1988 and 1993. After biopsy of the subcutaneous nodules, Itraconazole (200 mg), an anti-fungal drug, was orally administered for the lesion in the right lung for about 6 months. Since the tumor image revealed no improvement through this treatment, the tumor was resected. Histopathological examination by Grocott staining demonstrated the spherical form Coccidioides, i.e., endospores. Only 5 cases of resected pulmonary coccidioidal lesions have been reported in Japan including this case. We must be careful when handling coccidioidal culture because of its strong infectiosity.

Adult↗
PubMed1996

Asymptomatic colorectal cancer detected by screening.

PURPOSE: Colorectal cancer screening has become prevalent. To discuss the efficacy of screening, we studied the characteristic of asymptomatic colorectal cancer detected by screening. METHODS: This is a retrospective review of patients with colorectal cancer treated at our institution. During the past 20 years, 96 of 1,046 cases of colorectal cancer were asymptomatic and detected by screening. Sixty-one of these cases were detected in the recent five years. The initial screening procedures were fecal occult blood test in 51 cases, sigmoidoscopy or colonoscopy in 18, barium enema in 9, and other tests in 18. RESULTS: Thirteen lesions (14 percent) were smaller than 1.0 cm and 32 (33 percent) were 1-2 cm in size. There were 34 Tis, 21 T1, and 8 T2 tumors. Of the 55 Tis or T1 lesions, 14 showed nonpolypoid growth (5 flat-elevated, 7 flat-elevated with depression, 1 flat, 1 depressed), and 12 of these were detected on endoscopy. Thirty-four cases were TNM Stage 0, 25 were Stage I, 16 were Stage II, 12 were Stage III, and 9 were Stage IV. Sixty-one percent of those detected by screening were in either Stage 0 or Stage I compared with 16 percent in the symptomatic group. Cumulative five-year disease-free survival rates were 100 percent for both Stage 0 and Stage I, 94 percent for Stage II, and 52 percent for Stage III. Overall cumulative five-year survival rate was 87 percent for those detected by screening, compared with 57 percent in symptomatic patients. CONCLUSIONS: Asymptomatic cancers detected by screening were at a less advanced stage. In particular, many nonpolypoid early cancers were detected by endoscopic screening.

Aged↗
PubMed1996

Corneal endothelial changes in schizophrenic patients with long-term administration of major tranquilizers.

PURPOSE: To examine corneal endothelial changes in schizophrenic patients who underwent long-term administration of major tranquilizers. METHODS: We performed slit-lamp examination and endothelial specular microscopy on 100 eyes of 50 schizophrenic patients (range, 31 to 68 years old; mean, 54 years) who underwent long-term (12 to 44 years) treatment with major tranquilizers. We also studied 50 eyes of 25 patients (range, 31 to 65 years old; mean, 53 years) with no history of corneal disease, as a control group of similar age. Mean cell density, coefficient of variation, and percentage of hexagonal cells were calculated and statistically compared between patients and controls using an unpaired t-test. RESULTS: Slit-lamp examination disclosed pigmentation of the cornea in nine eyes of five patients and pigmentation of the lens in 25 eyes (25%) of 35 patients. Corneal pigmentary changes were seen only in patients with lenticular changes. No eyes showed corneal edema. In contrast, no corneal abnormalities were seen in any control eye. Specular microscopic analysis showed mean cell density of 3,484.4 +/- 462.6 cells/mm2, coefficient of variation of 0.31 +/- 0.06 and percentage of hexagonal cells to be 60.2% +/- 7.5% in the patient group, and 3,291.3 +/- 384.4 cells/mm2, 0.32 +/- 0.07, and 60.6% +/- 7.0%, respectively, in the control subjects. There were no statistically significant differences between patient and control eyes in these three factors. The nine eyes with corneal pigmentation showed no significant differences in these three factors as compared with the control subjects. CONCLUSIONS: These results indicate that long-term treatment with major tranquilizers is not associated with morphometric abnormalities of the corneal endothelium.

Adult↗
PubMed1996

Cryopreservation of zona-hatched mouse blastocysts.

Experiments were conducted to determine the conditions for successful and efficient cryopreservation of hatched mouse blastocysts, using simple vitrification procedures. Hatched blastocysts were obtained by culture of morulae in vitro. Vitrification solutions used were EFS40 and GFS40, which were 40% (v/v) ethylene glycol and 40% (v/v) glycerol, respectively, diluted in PB1 medium containing 30% Ficoll (w/v) and 0.5 mol sucrose l-1. In the one-step method, embryos were directly exposed to the vitrification solutions at 25 degrees C for 0.5 or 2 min; in the two-step method, embryos were equilibrated with a dilute (10-20%, v/v) ethylene glycol or glycerol solution for 5-10 min, before a 0.5 min exposure to EFS40 or GFS40, respectively. They were then vitrified in liquid nitrogen. When the embryos were vitrified in EFS40, the post-warming survival rates, assessed by the re-expansion of the blastocoel during 16 h of culture, were higher in embryos that had hatched from the zona earlier (120-132 h after hCG) than in those hatched later (142-150 h after hCG); however, the highest survival rate was only 65%, which was obtained by a one-step method. When embryos were vitrified in GFS40, a high survival rate (89-94%) was obtained especially by the two-step methods. Vitrified blastocysts developed into live young just as well as did fresh blastocysts; survival was highest after transfer to recipients on day 3 or day 4 of pseudopregnancy. These findings show that hatched mouse blastocysts can be successfully cryopreserved by a simple vitrification method, and that a glycerol-based vitrification solution is more suitable than the corresponding ethylene glycol-based solution for the vitrification, probably because slower permeation of glycerol avoids toxic injury.

Animals↗
PubMed1996

[Malignant fibrous histiocytoma of spermatic cord: a case report].

A 52-year-old man presented with a painful, gradually enlarging mass in the left inguinal region. An ultrasound examination demonstrated a lobulated, heterogenous tumor 6.0 x 4.0 x 3.0 cm in diameter, which separated from the left testis and epididymis. Radical inguinal orchiectomy with wide en bloc local resection was performed. Histologic diagnosis was a malignant fibrous histiocytoma (MFH) with a giant cell variant. The patient underwent postoperative regional irradiation and has been alive without metastasis and local recurrence 3 months after the operation. Among the 19 patients with MFH of spermatic cord reported in Japan, only two cases were of giant cell type of MFH including the present case.

Genital Neoplasms, Male↗