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Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 667 records · Page 37Linked to original sources
PubMed1992

Phase II study of cis-diammine(glycolato)platinum, 254-S, in patients with advanced germ-cell testicular cancer, prostatic cancer, and transitional-cell carcinoma of the urinary tract. 254-S Urological Cancer Study Group.

A multicenter cooperative study was conducted to evaluate the clinical efficacy and safety of cis-diammine(glycolato)platinum (254-S), a second-generation anticancer platinum complex, in the treatment of genitourinary cancers. 254-S was given i.v. at 100 mg/m2 at 4-week intervals. As a result, 2 complete responses (CRs) and 8 partial responses (PRs) were obtained in 35 patients with transitional-cell carcinoma (TCC) of the urinary bladder or pyeloureter, 3 PRs were obtained in 16 subjects with prostatic cancer, and 6 CRs and 6 PRs were obtained in 15 patients with testicular cancer, generating objective response rates of 28.6% [95% confidence interval (CI), 14.6%-46.3%], 18.8% (95% CI, 4.0%-45.6%), and 80.0% (95% CI, 51.9%-95.7%), respectively. Bone marrow suppression was the dose-limiting toxicity, although it was reversible. Although no hydration was performed in approx. 40% of the patients, the incidence of nephrotoxic effects was low and most of those encountered were mild, the exception being one patient who showed severe renal insufficiency after the first treatment. Nausea and vomiting occurred in approx. 70% of the patients, but most gastrointestinal toxicities were controlled without antiemetic treatment. In addition, liver-function impairment was rarely observed. We conclude that 254-S is a promising cisplatin analogue for the treatment of genitourinary cancers and is worthy of further investigation in large-scale, randomized comparative studies with other platinum derivatives in both single-agent and combination regimens.

Adult↗
PubMed1992

Partial protection of 1 alpha-hydroxyvitamin D3 against the development of diabetes induced by multiple low-dose streptozotocin injection in CD-1 mice.

1 alpha-Hydroxyvitamin D3 (1 alpha-OH-D3), a precursor of active vitamin D3, 1 alpha,25-dihydroxyvitamin D3, was tested in CD-1 mice for its in vivo effect against the development of diabetes induced by administering multiple low doses of streptozotocin (STZ). Daily intraperitoneal (IP) injections of 35 mg/kg body weight of STZ administered for 5 consecutive days to mice from 7 weeks of age induced a delayed-onset hyperglycemia, insulitis, and beta-cell degranulation in 26 of 28 mice. Only 12 of 29 mice developed diabetes when treated with simultaneous daily IP injections of 1 alpha-OH-D3 for 14 consecutive days, with diabetes defined as a plasma glucose level greater than 200 mg/dL. A daily dose of 0.3 micrograms/kg 1 alpha-OH-D3 also protected against the development of hyperglycemia in five of 13 mice, whereas 0.2 micrograms/kg 1 alpha-OH-D3 was ineffective, indicating a dose-related effect. Histological study showed that, among the 1 alpha-OH-D3-treated mice, the pancreatic islets of euglycemic mice showed neither massive islet infiltration nor beta-cell degranulation, whereas those of the hyperglycemic mice showed insulitis. However, when diabetes was chemically induced with a single high dose of STZ, the simultaneous administration of 1 alpha-OH-D3 to mice failed to protect against the development of hyperglycemia; all five mice so treated developed hyperglycemia. Their pancreatic islets did not show insulitis. Therefore, it is suggested that 1 alpha-OH-D3 may protect against the development of diabetes following administration of multiple low doses of STZ, probably via an immune mechanism.

Animals↗
PubMed1992

Biological potency of a fluorinated vitamin D analogue in hypoparathyroidism.

Several in vivo experiments have revealed that a synthesized fluorinated analogue of vitamin D, 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 (26,27-F6-1,25(OH)2D3) has a higher and longer-lasting biological activity than 1,25(OH)2D3 in calcium regulating actions. We evaluated the biological potency and the availability for clinical use of this compound in hypocalcemia associated with hypoparathyroidism. In an experimental setting, daily administration of 650 pmol/kg of 26,27-F6-1,25(OH)2D3 showed an equivalent effect to that of 3250 pmol/kg of 1,25(OH)2D3 in elevating whole blood ionized calcium levels in parathyroidectomized rats. Furthermore, an additional clinical study demonstrated that 0.5-1.5 micrograms/day of 26,27-F6-1,25(OH)2D3 were considered adequate maintenance doses in various types of hypoparathyroidism and that changes of medication to the same doses of 1,25(OH)2D3 resulted in prompt decline of urinary calcium excretion and of whole blood ionized calcium levels, and in recurrence of symptoms related to hypocalcemia. Although the mechanism responsible for the high potency of this analogue remains unclear, our experience confirms that 26,27-F6-1,25(OH)2D3 has higher biological activities in bone calcium mobilization and is more potent than 1,25(OH)2D3 in correcting hypocalcemia of hypoparathyroidism in a hospital setting.

Animals↗
PubMed1992

Gastric cytoprotective anti-ulcerogenic actions of hydroxychalcones in rats.

The preventive effects of hydroxychalcone derivatives on ulcer formation induced by severe necrotizing agents such as 60% ethanol in 150 mM HCl (HCl-ethanol) and 0.2 N NaOH in rats were examined. Among the compounds tested, 2',4'-dihydroxychalcone gave the strongest activity in both experimental models and protected the gastric mucosa from the insult of either necrotizing agent at oral doses ranging from 1 to 10 mg/kg, as evidenced by a dose-related reduction in the ulcer index. The mucosal protective activity of 2',4'-dihydroxychalcone was not affected by pretreatment with indomethacin (5 mg/kg, s.c.). To investigate the detailed mechanism of the mucosal protective action of 2',4'-dihydroxychalcone, its inhibitory effects on the decrease in the hexosamine content from the gastric mucus induced by HCl-ethanol were studied by using it in combination with a dye, Alcian blue. As a result, 2',4'-dihydroxychalcone at an oral dose of 10 mg/kg inhibited the decrease in the dye-recovery from the gastric mucus induced by HCl-ethanol. PGE2 at an oral dose of 0.1 mg/kg exhibited a similar action. These results established that 2',4'-dihydroxychalcone is a potent cytoprotective agent similar to PGE2 effectively preventing gastric ulcer formation induced by strong necrotizing agents and seems to suggest that this compound protects the stomach against its own peptic secretions by reinforcement of gastric resistances. In fact, 2',4'-dihydroxychalcone prevented ulcer formation induced by water-immersion stress in rats and also showed a marked enhancement of the healing of acetic acid-induced gastric ulcers in rats.

Animals↗
PubMed1992

Evaluation of the in vitro antiproliferative properties of four novel anthracyclines YM1, 3, 4 and 6 in human leukemia cell lines.

The antitumor activity of novel doxorubicin analogues YM1, YM3, YM4 and YM6 was evaluated against drug sensitive U937 monocytic leukemia and CCRF-CEM lymphoid leukemia cell lines, as well as drug resistant CEM/VLB100 lymphoid multidrug resistant leukemia cell line by a [3H]thymidine incorporation assay. Different antileukemic activities of these new anthracyclines were observed in our studies. These novel anthracyclines produced a dose- and time-dependent inhibition in all the leukemic cell lines tested, while YM1 and YM3 were more effective than YM4 and YM6 against all the leukemic cell lines. The antitumor activity of all these novel analogues was lower than that of doxorubicin or epidoxorubicin in drug sensitive leukemic cells. The relative resistance values (IC50 of resistant cell line/IC50 of sensitive parental cell line) of YM1, 3, 4 and 6 were 27, 7, 5 and 14 respectively. These were lower than the resistance values for ADM and EDR which were 45 and 40 respectively. YM3 had a similar antileukemic activity against the CEM/VLB100 drug resistant leukemic cell line to ADM or EDR with a lower relative resistance value and a slightly increased IC50 value. Our results suggest that YM3 may be used in high dose for the clinical treatment of leukemias with possible less cardiotoxicity as well as less drug resistance.

Antineoplastic Agents↗
PubMed1992

Altered calcium homeostasis accompanying changes of regional bone mineral during a very-low-calorie diet.

Calcium homeostasis during a very-low-calorie diet (VLCD) was examined. During the treatment, intact parathyroid hormone tended to decrease initially, bone Gla-protein increased significantly in the third week, and tartrate-resistant acid phosphatase decreased during the entire treatment. Serum ketone bodies showed significant correlations with intact parathyroid hormone and bone Gla-protein in some cases. Regarding bone mineral content, bone mineral content of the head increased while that of the legs decreased, resulting in no significant changes in total bone mineral content. These results suggest that VLCD treatment alters calcium homeostasis, which may cause regional bone mineral changes.

Acid Phosphatase↗
PubMed1992

Role of adenosine receptor activation in myocardial infarct size limitation by ischaemic preconditioning.

OBJECTIVE: The aims were to examine the role of adenosine receptors in the mechanism of preconditioning in a chronic rabbit model of myocardial infarction; to assess whether the preconditioning effect is blocked by an adenosine receptor antagonist, 8-phenyltheophylline; and to determine whether an adenosine A1 receptor agonist, R(-)N6-2-phenylisopropyl adenosine (R-PIA), mimics infarct size limitation by preconditioning. METHODS: Myocardial infarction was induced in male rabbits by occlusion of the left coronary artery for 30 min, which was followed by 72 h reperfusion. Before the 30 min ischaemia, rabbits were subjected to one of the following six protocols: (1) untreated control; (2) intravenous injection of 8-phenyltheophylline; (3) preconditioning with 5 min ischaemia; (4) pretreatment with 8-phenyltheophylline plus preconditioning; (5) intravenous injection of R-PIA; or (6) R-PIA plus atrial pacing (240.min-1). Infarct size and area at risk were determined by histology and fluorescent particles, respectively. RESULTS: Preconditioning significantly limited infarct size, normalised as a percent of area at risk (%IS/AR), to 19.2 (SEM 2.3)% v control value of 46.5(2.8)%. 8-Phenyltheophylline alone did not modify the %IS/AR, but its injection before preconditioning attenuated the preconditioning effect such that IS/AR = 34.4(2.5)%. While R-PIA did not achieve statistically significant myocardial salvage, R-PIA plus atrial pacing limited infarct size to 33.7(3.0)% (p<0.05 v control). The R-PIA group had severe hypotension and their infarct sizes were inversely correlated with diastolic blood pressure at reperfusion. There was no such correlation in the R-PIA plus pacing group in which bradycardia and hypotension induced by R-PIA were attenuated by atrial pacing. CONCLUSIONS: The infarct size limiting effect of preconditioning was attenuated by 8-phenyltheophylline, and pretreatment with R-PIA was able to limit myocardial infarct size when severe hypotension was avoided by atrial pacing. These findings suggest that adenosine receptor activation plays a crucial role in the mechanism of preconditioning.

Animals↗
PubMed1992

[Outbreaks of acute gastroenteritis caused by small round structured viruses in Tokyo].

Of 34 non-bacterial gastroenteritis outbreaks which occurred at day-care centers, kindergartens, elementary and secondary schools in Tokyo during the period from February 1985 to June 1991, 28 outbreaks from which small round structured viruses (SRSV) were detected in the patients' stool specimens by electron microscopy were subjected to an epidemiological investigation. The outbreaks tended to occur frequently in the cold season; twenty-two (79%) of these outbreaks from November through April. Though detailed epidemiological informations was not obtained from all outbreaks, the common source of infection were presumed to be present in many of the outbreaks, judged from the incidence as to time course of patients. Food doubted to be incriminated as transmission vehicles in these outbreaks was served at schools, kindergartens, and lodgings. In some outbreaks, SRSV was detected from stool specimens of food handlers, or they were seroconverted to SRSV, suggesting that food was incriminated as a transmission vehicle. The symptoms of patients differ slightly from age to age: in the age range of 0 to 6 years, vomiting 90%, fever 41% and diarrhea 32%; in the 6 to 12 year-olds, nausea 61%, vomiting 48%, abdominal pain 65%, diarrhea 20% and fever 29%; and in the 12 to 15 year-olds, nausea 69%, vomiting 42%, abdominal pain 60%, diarrhea 30% and fever 34%. The lower the age of patient vomiting was more frequently observed. In these lower age groups, the frequency of nausea and vomiting tended to exceed that of diarrhea.

Adolescent↗
PubMed1992

Comparison of the myotonic dystrophy associated CTG repeat in European and Japanese populations.

Gene amplification using polymerase chain reaction (PCR) was carried out on DNA samples from a total of 92 normal subjects and 52 subjects with myotonic dystrophy (DM) from European and Japanese populations, to determine the copy number of the CTG repeat associated with DM for each group. In the two populations, the number of repeats on normal chromosomes only were compared, as CTG copy number on DM chromosomes was difficult to determine by PCR alone. In this study, normal chromosomes were found which had as many as 35 copies of the repeat, which is larger than the normal range reported previously but still does not overlap with the repeat number associated with DM pathology, which is at least 50 copies. Using data from normal chromosomes from unrelated subjects, the frequencies of five, 11, and 13 copies of the CTG repeat were found to be significantly different between the two populations, with five and 11 copies more commonly seen in the European population and 13 copies in the Japanese population. This difference may be the result of natural divergence of the normal chromosomes between the population groups.

Alleles↗
PubMed1992

Syntheses of 2-(3,4-dimethoxyphenyl)ethylamine derivatives and their antiulcer activities.

A series of acyl derivatives of 2-(3,4-dimethoxyphenyl)ethylamine (4) were synthesized and evaluated for their effectiveness to prevent water-immersion stress-induced gastric ulceration when given intraperitoneally to rats. Among them N-[2-(3,4-dimethoxyphenyl)ethyl]-2-phenylaminoacetamide hydrochloride (15) had significant antiulcer activity. Further modification of the four parts of 15 revealed that only the introduction of a carbamoyl group into 2- or 3-position of the phenylamino part gave compounds (49-51, 54 and 55) which retained antiulcer activity comparable to the lead compound. However, the compounds (49-51 and 54) did not exert a prophylactic effect when administered orally except for the 3-substituted bezamide derivative 55. Alkyl substitution on the nitrogen of benzamide gave 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl] amino-N-methylbenzamide (66, DQ-2511) and the related compounds (67, 70, 74 and 77) which all had potent antiulcer activities at oral doses of 50-400 mg/kg.

Animals↗
PubMed1992

[Affected siblings with Alzheimer's disease had missense mutation of codon 717 in amyloid precursor protein gene].

Using reverse genetic techniques, the gene responsible for familial Alzheimer's disease (FAD) is one of the clues to identify the pathogenesis of Alzheimer's disease (AD). Recently a missense mutation in the APP (amyloid precursor protein) gene (generally this mutation was called APP717) was detected in 2 Caucasian AD families and the same mutation was found in 3 Japanese AD families. We experienced brother's cases who were diagnosed as AD. Both of them and one normal person of the next generation had APP717. The first symptom of the elder brother (case 1) was forgetfulness at 52 years old, then dementia was advanced. In his clinical course there were characteristic findings such as the mirror sign, pseudodialog and jargon which has been rarely described in the Japanese literature. Finally he died of pneumonia at 57 years old. He was diagnosed as AD pathologically and physical findings of brain CT, SPECT (single photon emission computed tomography) and EEG supported this diagnosis clinically. The first symptom of the younger brother (case 2) was also forgetfulness at 45 years old, then severe dementia was advanced, at last he died of pneumonia at age 53 old. On the other hand the mother of the brothers died of severe dementia, so it was suspected that brothers died of severe dementia, so it was suspected that she had had AD. The clinical courses and pathological findings were thought to be typical of AD, namely there were no significant differences in comparison with other cases of FAD and sporadic AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1992

[Two kindreds with familial Alzheimer's disease--analysis of the APP717 mutation and the mutated genes for the prion protein].

Numerous Caucasian familial Alzheimer's disease (FAD) pedigrees have been described in the literature, while only 21 Japanese FAD families have been reported to date. Here we report the clinical findings and the result of molecular genetic analysis of 4 patients from two FAD kindreds, OS-2 and OS-3. The proband in OS-2 family has developed loss of recent memory and place disorientation age at 43. A brain CT showed severe diffuse cortical atrophy. Her younger brother had dementia at 42 years and her mother and other 3 siblings had also dementia symptoms suspected to be Alzheimer's disease. The proband in OS-3 family showed declining recent memory at 49 years and developed dysphagia, gait disturbance and emotional incontinent with cerebral atrophy at 52 years. His father and elder brother demonstrated dementia signs at 60 and 54 years old, respectively. Recently it was reported that affected members from 2 Caucasian kindreds with FAD had missense mutation in exon 17 of the gene for amyloid precursor protein (APP). Patients from three different Japanese kindreds with FAD also showed the same mutation on the APP gene. Amino acid substitution (Val-Ile) at codon 717 by this mutation is responsible for FAD in at least some kindreds. We used genomic DNA from 4 affected members of 2 families to determine whether the disease in these families is associated with a APP717 mutation and the mutated codons, 102, 117, 129, 178 and 200, on the gene for protease-resistance prion protein (PrP) which cause transmissible dementia, Creutzfelt-Jacob disease (CJD) and Gerstmann-Strausler syndrome (GSS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Dysuria in male elderly outpatients evaluated by a questionnaire survey].

We surveyed complaints of dysuria in male elderly outpatients by questionnaire survey. Seven hundred and twenty outpatients (39 aged 30-39, 63 aged 40-49, 170 aged 50-59, 229 aged 60-69, and 219 aged 70 or more) visiting our outpatient internal medicine clinics were asked by a questionnaire about the subjective symptoms of dysuria, including frequencies of nocturia, prolongation of the start of urination, straining at urination, and residual urine, graded as asymptomatic, mild, moderate and severe. The subjects were divided into three groups as to the dysuria; normal group without symptoms or one mild symptom, borderline group with two or more mild symptoms, and dysuria group with one moderate or severe symptom or more. The rates of the patients in the dysuria group were increased with age, being 15%, 16%, 21%, 31% and 53%, respectively, in the above-mentioned age groups. This finding emphasized the importance of questions about dysuria in elderly patients also in internal medicine outpatient clinics, and of differential diagnosis for the causal factor(s) for dysuria in elderly patients including benign prostate hypertrophy.

Adult↗
PubMed1992

[Drug compliance in the elderly].

In order to clarify the characteristics of elderly patients concerning their attitudes toward taking prescribed medicine, self-reported compliance with prescriptions was compared among different age groups. We performed a survey in 626 outpatients and their attending physicians in 4 of our affiliated hospitals, and analyzed self-reported compliance by the patients to the prescription and their answers to questions related to drug-taking along with the diagnoses and prescriptions reported by the physician. The number of prescribed medicine was 2.3 tablets on the average for patients younger than 40, while 5.1 tablets were prescribed for patients over 70. However, self-reported compliance was best in patients over 70 than in other age groups. Compliance was good in 76% of patients who answered that the amount of medicine was appropriate, while good compliance was lower in those who thought the prescription excessive (67%). Likewise, compliance of patients who had concerns with drug side effects or who were not feeling well under medication was lower than that of patients who felt well under medication. Prescriptions for after lunch were most liable to be forgotten than those for other times of the day. Moreover, a high percentage of elderly patients attended more than 2 departments or medical facilities, and one third of those patients did not inform the physician of the fact suggesting that they were at higher risks of overdosing and unexpected drug interaction. Furthermore, the percentage of patients who did not receive explanation from physicians was higher in the elderly thus demonstrating that elderly patients have quite different characteristics in attitude with regard to medicine from younger age group patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Surveillance after orchiectomy for stage I testicular seminoma].

The results of treatment by orchiectomy and radiotherapy for stage I testicular seminoma are excellent with cure rates exceeding 95% and relapse rates less than 5%. However, after the development of successful surveillance programs for stage I nonseminomatous testicular cancers, the role of radiotherapy has been questioned by some authors and they proposed a "surveillance policy" for these patients. The purpose of this study was to determine the percentage of patients cured by orchiectomy alone, percentage who ultimately required therapy for occult metastases, site of recurrence, and over-all cure rate and treatment morbidity. And these data were compared with those of adjuvant radiotherapy group retrospectively. Twenty seven patients were treated with adjuvant radiotherapy (RT group). Since 1986, 23 patients with stage I testicular seminoma entered the "surveillance only" protocol at our institution (S group) with a follow-up between 14 and 70 months (median 43 months). Informed consent for the policy of surveillance was obtained. Follow up consisted of physical examination, determination of serum tumor markers and chest X-ray bimonthly for 2 years, every 3 months for 1 year, every 6 months for 2 years and annually thereafter to 10 years. CT scans were performed every 4 months for 3 years, every 6 months for 2 years. Two patients in S group (8.7%) relapsed at 4 and 7 months after orchiectomy with nonbulky retroperitoneal disease (less than 5 cm in diameter), whereas only 1 (3.7%) irradiated patients did so after 4 months.

Adult↗
PubMed1992

Expression of intermediate filaments and other special markers by testicular germ cell tumors. With reference to embryogenesis.

Distribution of intermediate filament proteins (IFs) and several special markers was studied in 39 testicular germ cell tumors and 8 embryos and foetuses. The similarity and difference between development of germ cell tumor and embryogenesis were immunohistochemically investigated. Seminoma and embryonal carcinoma, as tumoral counterparts of undifferentiated germ cells, were characterized by little IF expression. This study revealed that the maturing and differentiating process in germ cell tumor is different from normal embryonal development and the tumor cells showed leaping maturing steps in tumorigenesis. Immunostaining for IFs helped to discover the further differentiation occurring in embryonal carcinoma and to demonstrate heterogeneous elements in non-seminoma germ cell tumors, which sometimes might not be apparent by light microscopical observation of H&E staining section. According to the findings, two patterns in mixed germ cell tumors are suggested; i.e., combined and diffuse types. The mechanism of tumorigenesis of the two types is supposed to be different. Clinically, the prognosis of most patients with testicular germ cell tumor is fairly good because of the improved chemotherapies that are dependent on histological diagnosis.

Adolescent↗
PubMed1992

A two-site immunochemiluminometric assay for intact parathyroid hormone and its clinical utility in hemodialysis patients.

Measurement of serum parathyroid hormone (PTH) concentrations is complicated by the fact that there are several fragments of the hormone in the circulating as a result of the metabolism of PTH. The best way to study the secretory activity of the parathyroid glands directly may be to measure the biologically active intact PTH molecule. Recently, it has become possible to overcome these limitations by application of the two-site immunoradiometric assay (IRMA) to the measurement of intact PTH. The two-site immunometric technique has been applied to the two-site immunochemiluminescent assay (ICMA) for the measurement of circulating intact PTH. To evaluate the utility of measurements of serum intact PTH by two-site ICMA in hemodialysis patients, two-site ICMA and IRMA were compared in 104 hemodialysis patients. We found a good correlation (r = 0.93) between values obtained by ICMA and by IRMA. Although serum intact PTH by ICMA was significantly suppressed by rising plasma ionized calcium after a session of hemodialysis in 29 patients, mid-region PTH did not show a significant change. This result suggests the intact PTH assay is more suitable for the earlier detection of secondary hyperparathyroidism than the mid-region assay and may be useful for precise assessment of clinical status and response to therapeutic intervention designed to correct the progressive bone disease in hemodialysis patients. We conclude that two-site ICMA for serum intact PTH which could be measured without radioisotopes nor scintillation counter is as useful as IRMA in hemodialysis patients.

Humans↗