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Biomedical subjects

K Nagao

Publications and source records attributed to K Nagao.

At least 73 records · Page 4Linked to original sources
PubMed2000

[A phase II study of irinotecan combined with cisplatin in non-small cell lung cancer. CPT-11 Lung Cancer Study Group].

Based upon the results of phase I study of irinotecan (CPT-11) combined with cisplatin (CDDP) on non-small cell lung cancer (NSCLC), a combination phase II study on NSCLC was carried out from Feb., 1992 to Sep., 1992. CPT-11 (60 mg/m2) and CDDP (80 mg/m2) were administered by i.v. drip infusion, with administration schedules of Days 1, 8, 15 and only Day 1, respectively. This therapy course was repeated every 4 weeks. Subjects were NSCLC patients of stage III B or IV disease. Those without prior chemotherapy (Group A) and those with prior therapy (Group B) were enrolled separately. Seventy patients were entered into Group A and 32 patients into Group B. One of the patients of Group A was ineligible. The characteristics of the eligible cases of Group A were: male/female, 51/18; median age, 61 years old; PS 0/1/2, 18/39/12; stage IIIB/IV, 26/43; and adeno/squamous/large, 51/15/3. Those of group B were: male/female, 20/12; median age, 62 years old; PS 0/1/2, 5/18/9; stage I/IIIB/IV, 1/7/24, adeno/squamous/large/ad-sq, 28/2/1/1. Thirty-three patients (47.8%) responded in Group A and B patients (25.0%) responded in Group B. Major adverse reactions (grade 3 or higher) of Group A/Group B were neutropenia (80.3%/73.3%), anemia (35.3%/34.4%), diarrhea (18.8%/28.1%) and nausea/vomiting (34.8%/34.4%). Median survival times for Group A and Group B were 308 and 295 days, respectively. CPT-11 in combination with CDDP is effective against NSCLC, suggesting that further studies are needed to determine the usefulness of this therapy.

Adult↗
PubMed2000

[Effect of cholesterol reducing therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on secondary prevention after myocardial infarction in Japanese patients].

Lowering the blood cholesterol level is a safe method to improve survival for primary and secondary prevention of coronary heart disease. However, there is no evidence for any effectiveness in Japanese. This study was designed to evaluate the effect of cholesterol lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitor on cardiac events(death and reinfarction) in Japanese patients after myocardial infarction. A total of 290 patients after myocardial infarction were studied retrospectively. The patients were divided into 2 groups with or without HMG-CoA reductase inhibitor therapy for lowering blood cholesterol levels. The cumulative cardiac events and percentage change of cholesterol levels[total cholesterol and low-density lipoprotein (LDL) cholesterol level] were compared between the 2 groups. HMG-CoA reductase inhibitor therapy lowered plasma cholesterol levels significantly (total cholesterol level--11 +/- 20%, LDL cholesterol level--23 +/- 26%) in patients with hypercholesterolemia, whereas there was no change(total cholesterol level 4.3 +/- 22%, LDL cholesterol level--7.2 +/- 24%) in patients without hypercholesterolemia. HMG-CoA reductase inhibitor therapy reduced cardiac events significantly compared in patients with hypercholesterolemia(p = 0.0008), but there was no benefit in patients without hypercholesterolemia. We suggest that treatment with HMG-CoA reductase inhibitor therapy for lowering cholesterol levels was effective for secondary prevention after myocardial infarction in Japanese patients with hypercholesterolemia.

Anticholesteremic Agents↗
PubMed2000

[A case of gastric cancer with multiple liver metastasis responding to combined chemotherapy with low-dose cisplatin and 5-fluorouracil].

A 68-year-old man who had Borrmann type 4 gastric cancer with multiple liver metastases was admitted to our hospital on October 20, 1998. He was considered nonresectable and placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU. After 9 weeks of administration, the liver metastases had disappeared on abdominal computed tomography, but the primary lesion had progressed. On May 12, 1999, a total gastrectomy with a partial resection of the transverse colon and resectional biopsy of a white nodule of the liver were performed. This was a non-curative operation because of the peritoneal dissemination. A histopathological examination of the liver nodule revealed that the cancer cells had disappeared. The patient had an uneventful postoperative course and 4 weeks of chemotherapy were added. He remains alive with no symptoms or re-growth of the liver metastatic tumor 4 months after the surgery.

Adenocarcinoma↗
PubMed2000

[A questionnaire survey on the self-assessment to the asthmatic treatment in Saitama Prefecture: results from 2825 cases].

The aim of this study was to survey the self-assessment to the treatment of adult bronchial asthmatics in Saitama prefecture. A questionnaire on daily symptoms and medications was distributed to 2825 adult asthmatic subjects who were treated at 125 hospitals/clinics in Saitama prefecture between September 15th and October 30th 1998. More than half (52.7%) of patients described that their general condition of asthma was poorly controlled. Even among the patients described that their condition was good or fair, 30.2% of them had some asthmatic symptoms such as shortness of breath or nocturnal awakening. Although inhaled corticosteroids were used in 66.2%, the ratio of patients who used spacer and kept drug compliance as prescribed were 59.6% and 45.8%, respectively. According to the physician's reports, cysteinyl leukotriene antagonist was used in 35.7%, which was comparable to the total of another anti-allergic drugs (37.3%). These results suggest that more than half of asthmatic patients in Saitama prefecture were not satisfied with their conditions of the disease control. Furthermore, more thorough education on the technique and compliance of inhaled corticosteroids would be required.

Adolescent↗
PubMed1999

Amyotrophic lateral sclerosis: increased hyaluronic acid in the media of the basilar artery.

Hyaluronic acid in the basilar artery of 10 patients with sporadic amyotrophic lateral sclerosis (ALS) and 7 age-matched control subjects was examined histochemically and densitometrically. The intensity of staining with alcian blue was significantly increased (P=0.0007) in the media in ALS patients compared with that in control subjects. The staining was virtually eliminated by Streptomyces hyaluronidase. These results clearly indicate an increase of hyaluronic acid in the media of the basilar artery in ALS patients.

Aged↗
PubMed1999

Alteration in amino acids in motor neurons of the spinal cord in amyotrophic lateral sclerosis.

Little is known concerning the changes of amino acid composition in different regions of the spinal cord in patients with amyotrophic lateral sclerosis (ALS). We performed quantitative amino acid analyses in the posterior funiculus, the lateral corticospinal tract, and the anterior horn of cervical enlargement of the spinal cord from seven ALS patients, and the results were compared with those of seven patients with other neurologic diseases (control A) and seven patients without neurologic diseases (control B). The levels of collagen-associated amino acids, hydroxyproline, proline, glycine, and hydroxylysine, were markedly lower in the lateral corticospinal tract and the anterior horn of ALS patients than in controls A and B. The contents of the acidic amino acids glutamate and aspartate were also significantly decreased in the lateral corticospinal tract and the anterior horn of ALS patients as compared with those of controls A and B. These data suggest that decreased contents of collagen-associated amino acids and excitatory amino acids are related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS.

Adult↗
PubMed1999

Mucoepidermoid carcinoma arising in the accessory parotid gland.

A rare case of a 9-year-old female with mucoepidermoid carcinoma arising in the accessory parotid gland is reported. She had complained of a painless and round mass of the left cheek for a duration of 14 months. Sialography, ultrasonography, CT scan and MRI were performed preoperatively. Sialography revealed a small duct separating from the Stensen's duct. CT and MRI showed that the tumor with smooth outline was lying on the masseter muscle and detached from the main parotid gland. The preoperative diagnosis was an accessory parotid gland tumor. The tumor was removed without facial nerve injury via standard parotidectomy incision. The tumor was composed of mucous and epidermoid cells. The pathological diagnosis was low-grade mucoepidermoid carcinoma.

Carcinoma, Mucoepidermoid↗
PubMed1999

Diagnostic problems of evaluating vertebral metastasis from breast carcinoma with a higher degree of malignancy.

BACKGROUND: Bone metastases from breast carcinoma are frequently observed as postoperative pathologic conditions; however, in many cases, diagnosis and treatment are difficult. Although most diagnoses of bone metastases are made by plain radiography (X-P) or bone scintigraphy, the use of magnetic resonance imaging (MRI) has enabled detailed imaging of foci, and many more lesions have become detectable. In the current study, the authors evaluated the relation between the diagnosis of bone metastases of breast carcinoma and clinicopathologic factors, especially those of proliferative activity and effects of treatment. METHODS: The subjects consisted of 51 breast carcinoma patients (mean age, 51.2 years) with vertebral metastases diagnosed by plain radiography, bone scintigraphy, or MRI. Twenty-eight of the 51 patients were premenopausal and 27 of the 51 had bone metastases only. The patients were classified into the following groups: Group A, 24 patients who showed similar findings in plain radiography, bone scintigraphy, and MRI; Group C, 14 who showed no abnormalities on radiography or bone scintigraphy but whose lesions were diagnosed by MRI only; and Group B, 13 patients with findings intermediate between Groups A and C. The proliferative activity of tumors was evaluated by determining the level of DNA polymerase alpha. RESULTS: Regarding the relation to clinicopathologic factors, a significant number of patients with estrogen receptor (ER) negative tumors who had a high level of DNA polymerase alpha, short disease free intervals (DFI), and metastases to other organs were included in Group C. Prognoses of patients in Group C were poor. CONCLUSIONS: For the diagnosis of breast carcinoma with bone metastasis, different correlations were noted among the various biologic characteristics, such as ER status and proliferative activity. That is, bone scintigraphy sufficiently reflected foci in patients with ER positive tumors or tumors with low proliferation, whereas bone scintigraphy was false-negative in patients with ER negative or highly proliferative tumors, showing that MRI was useful in diagnosing such patients. Therefore, consideration of malignant features, such as proliferative activity and ER status, is believed necessary during the postoperative follow-up of breast carcinoma patients.

Adult↗
PubMed1999

Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative.

JTT-501, 4-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-3,5-isoxaz olidinedione, is an isoxazolidinedione derivative which is structurally distinct from thiazolidinediones such as pioglitazone and troglitazone. We investigated the effects of JTT-501 on insulin-sensitizing activity and in rodent diabetic models. JTT-501 enhanced insulin-stimulated cell differentiation of 3T3-L1 fibroblasts with an EC50 value of 110 nM. Furthermore, JTT-501 activated peroxisome proliferator-activated (PPA) gamma and alpha receptors with the EC5-fold values of 0.28 and 5.4 microM, respectively. In the non-insulin-dependent diabetes mellitus model KK-Ay mice, JTT-501 improved hyperglycemia, hyperinsulinemia and hypertriglyceridemia, and enhanced insulin-stimulated glucose oxidation in adipose tissues. JTT-501 was also effective in the non-insulin-dependent diabetes mellitus model Zucker diabetic fatty (ZDF) rats but not in the insulin-dependent diabetes mellitus model streptozotocin-induced diabetic mice. These observations suggest that JTT-501 enhances insulin sensitivity in peripheral tissues and improves hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in non-insulin dependent diabetes mellitus models. In particular, the triglyceride-lowering activity of JTT-501 is a unique characteristic compared to the thiazolidinediones. Therefore, JTT-501 may be a promising antidiabetic agent for treating non-insulin-dependent diabetes mellitus patients with insulin resistance.

3T3 Cells↗
PubMed1999

Apoptosis in breast cancer and its relationship to clinicopathological characteristics and prognosis.

BACKGROUND AND OBJECTIVES: Apoptosis is essential to maintain homeostasis in living organisms and occurs in a variety of tissues in response to both physiological and pathological stimuli. In breast cancer, most cytotoxic drugs and hormonal treatments induce apoptosis. We studied the relationships between apoptosis and clinicopathological variables or prognosis in 143 patients with operable breast cancer. METHODS: Apoptosis was numerically graded in 5 consecutive 40x high-power fields (HPF) of hematoxylin-eosin (H&E) stained sections, since we showed that there was a significant correlation of H&E staining with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. RESULTS: The average number of apoptotic cells was 19.9 (0 approximately 168)/5 HPF, and cases were classified into 3 groups based on the number of apoptotic cells/5HPF: 0 to 10, 11 to 30, and 31+. The level of apoptosis increased with increasing size of the tumor, and apoptosis was rarely seen in tumors with positive ER or lower proliferative activity, as assessed by DNA polymerase alpha. As shown by DNA content analysis, apoptotic cells were observed more frequently in tumors with low G1 and high S-phase fractions. In addition, apoptosis was correlated with overexpression of p53 and poor prognosis. Although apoptosis did not correlate with EIC (extensive intraductal component) status, tumors with comedo component had higher values of apoptosis than those without comedo component. CONCLUSIONS: In breast cancer, apoptosis might reflect biological behavior, namely a higher degree of biological aggressiveness and unfavorable prognosis.

Adult↗
PubMed1999

Telomerase reverse transcriptase mRNA expression and telomerase activity in hepatocellular carcinoma.

Human telomerase reverse transcriptase (hTERT) has been identified as the catalytic subunit of human telomerase. To clarify the clinical significance of hTERT mRNA in hepatocellular carcinoma (HCC), we investigated the relationship between telomerase activity and hTERT mRNA in human HCC and non-HCC tissues. The hTERT mRNA was detected in 17 (89.47%) of 19 livers with HCC and in 4 (21.05%) of 19 noncancerous tissues from these livers. Telomerase activity was detected in 17 of the 19 tumor tissues (89.47%) and in 4 of the 19 nontumor tissues (21.05%). The hTERT mRNA was detected in all tissues that were telomerase-positive and it was undetected in all tissues that were telomerase-negative. The correlation between the expression of hTERT mRNA and human telomerase activity in this study indicates that hTERT mRNA could be useful to diagnose cancer. Also, as telomerase production may be under the control of hTERT mRNA, the possibility is great that noncancerous liver tissue with chronic liver diseases acquires HCC when the hTERT mRNA is positive.

Adult↗
PubMed1999

Ethanol-extracted soy protein isolate results in elevation of serum cholesterol in exogenously hypercholesterolemic rats.

Soy protein preparations were reported to have hypocholesterolemic actions in experimental animals and humans, while the active components and the mechanism by which this occurs are not clarified yet. The objective of this study is to address these issues by using exogenously hypercholesterolemic rats which are susceptible to dietary cholesterol. Two groups of five rats (male, 12-wk-old) were fed on AIN 93G-based diet with soy protein isolate (SPI) or ethanol-extracted SPI (EE-SPI) for 2 wk. EE-SPI was prepared by ethanol extraction to remove isoflavones and other components. Concentrations of serum and liver total cholesterol were lower in rats fed SPI than in those fed EE-SPI. The abundances of mRNA for 7alpha-hydroxylase and low density lipoprotein receptor in the liver were lower in EE-SPI group than those in SPI group. These results suggest that the ethanol extract from SPI has a factor(s) to alleviate hypercholesterolemia by increasing the removal of cholesterol from serum through the receptor pathway and then from liver through enhancement of bile acid synthesis.

Animals↗
PubMed1999

Effect of gemfibrozil on triacylglycerol synthesis and secretion by liver and lipoprotein lipase activity in adipose tissue of rats.

The role of gemfibrozil, a hypotriglyceridemic drug, in synthesis, secretion and catabolism of triacylglycerols (TG) in rats was assessed. Chow diet-fed Sprague-Dawley rats were given various doses of gemfibrozil (10, 30 and 100 mg/kg body weight) for 2 weeks. Rats receiving the drug at the lowest dose significantly lowered the concentration of serum TG and apolipoprotein (apo) B in comparison with control rats. Synthesis of fatty acids from [14C]acetate and esterification of [14C]oleate to TG by the liver were not suppressed by the drug. Secretion rates of TG and apo B, measured by the Triton method, were suppressed at the highest dose. Lipoprotein lipase activity of the acetone powder prepared from adipose tissue was not influenced by the drug. These results indicate that the primary cause of hypotriglyceridemic action of gemfibrozil is not due to suppressing synthesis and secretion of TG by the liver or enhancing lipoprotein lipase activity in adipose tissues.

Acetates↗
PubMed1999

Cauda equina syndrome complicating pneumococcal meningitis.

A 14-month-old female with pneumococcal meningitis presented with flaccid paraplegia, saddle anesthesia, and bladder and bowel dysfunction. Magnetic resonance imaging of the spine demonstrated intense gadolinium enhancement of the cauda equina, whereas the conus medullaris appeared normal. This finding indicated that lumbosacral polyradiculopathy caused her symptoms.

Cauda Equina↗
PubMed1999

Cystic partially differentiated nephroblastoma in an adult: an immunohistochemical, lectin histochemical and ultrastructural study.

AIMS: Cystic partially differentiated nephroblastoma (CPDN) is an uncommon renal multicystic tumour, usually affecting early infants. To our knowledge, this report describes the first case of CPDN occurring in an adult. METHODS AND RESULTS: A 45-year-old man was found incidentally to have a left renal cystic tumour, measuring 20 mm in diameter, at the lower pole far from the pelvis. The tumour was composed of multilocular cystic spaces of variable size and intervening septa without solid nodular areas. The cysts were lined by a single layer of flattened, hobnail, or columnar epithelium. The septa were made of mesenchymal cells, which were admixed with small numbers of loosely aggregated blastemal cells, occasional tubular structures in various stages of development, and a few glomeruloid structures. The tumour cells had no anaplasia, and mitoses were rare. Immunohistochemical and lectin histochemical studies revealed that the cyst lining epithelium and the tubular structures in the septa expressed predominantly the markers for distal tubules and collecting ducts. Ultrastructurally, the cyst lining cells closely resembled collecting duct cells while some tubular structures showed an immature nephrogenic morphology. The patient was alive and well without evidence of recurrence 11 months after surgery. CONCLUSIONS: CPDN does occur in adults, as experienced in Wilms' tumour, though its incidence is extremely low. This study suggests that CPDN may show maturation intermediate between cystic nephroma and Wilms' tumour, even in adult cases.

Biomarkers, Tumor↗
PubMed1999

4-chloro-m-cresol triggers malignant hyperthermia in susceptible swine at doses greatly exceeding those found in drug preparations.

BACKGROUND: Chlorocresols are used as preservatives in numerous commercial drugs that have been shown to induce myoplasmic Ca2+ release; the most potent isoform is 4-chloro-m-cresol. The aims of this study were to (1) examine the in vivo effects of 4-chloro-m-cresol on swine susceptible to malignant hyperthermia and (2) contrast in vivo versus in vitro dose-response curves. METHODS: Susceptible swine (weight: 38.5 kg+/-3.55 kg) were anesthetized and monitored for variations in physiological responses, including end-tidal CO2, heart rate, blood pressure, blood chemistry, and temperatures. In the first animals studied, 4-chloro-m-cresol, at equivalent cumulative doses of 0.14, 0.28, 0.57, 1.14, 2.27, 4.54, and 9.08 mg/kg (n = 3; 12.5, 25, 50, 100, 200, 400, and 800 micromol) were administered, and in a second group, larger doses were used: 1.14, 3.41, 7.95, 17.04 (n = 4), and/or 35.22 (n = 1) mg/kg (100, 300, 700, 1,500, and/or 3,100 micromol). For comparison, in vitro rectus abdominis muscle preparations obtained from normal and susceptible swine were exposed to 4-chloro-m-cresol, at cumulative concentrations of 6.25, 12.5, 25, 50, 100, 200, 400, 800, and 1,600 micromol; standard caffeine and halothane contracture testing was also performed. RESULTS: Episodes of malignant hyperthermia were not triggered in response to administration of low doses of 4-chloro-m-cresol, but transient cardiovascular reactions (e.g., tachycardia, arrhythmias, and hypotension) were observed. Subsequently, episodes in these animals were triggered when halothane (0.87; 1 MAC) and succinylcholine (2 mg/kg) were given. Animals administered the higher doses of 4-chloro-m-cresol all had fulminant episodes of malignant hyperthermia that were fatal, when equivalent cumulative concentrations were greater than 1,500 micromol. The levels of 4-chloro-m-cresol in the plasma rapidly decreased: e.g., 5 min postadministration of the 1,500-micromol dose, the mean plasma level was only 52+/-18 micromol (n = 4). Hemolysis was detected following 4-chloro-m-cresol administration at concentrations > 200 micromol. In vitro, muscle from susceptible animals elicited contractures > 200 mg at 50-micromol bath concentrations of 4-chloro-m-cresol (n = 29), whereas normal muscle did not elicit such contractures until bath concentrations were > 800 micromol (n = 10). CONCLUSIONS: 4-chloro-m-cresol is a trigger of malignant hyperthermia in susceptible swine, but only when serum concentrations are far above those likely to be encountered in humans. A relatively low concentration of 4-chloro-m-cresol, 50 micromol, is sufficient to activate sarcoplasmic [Ca+2] release in vitro (e.g., contractures); this same bolus dose administered in vivo (0.57 mg/kg) has minimal effects due to the rapid decrease in its plasma levels.

Animals↗
PubMed1999

Increased type III procollagen in serum and skin of patients with amyotrophic lateral sclerosis.

OBJECTIVES: Collagen abnormalities of skin have been reported in patients with amyotrophic lateral sclerosis (ALS). However, little is known concerning the aminoterminal propeptide of type III procollagen (PIIIP) and type III collagen in ALS. The aim of this study is to measure PIIIP, a precursor form of type III collagen, in skin and serum of ALS. MATERIAL AND METHODS: We studied PIIIP immunoreactivity of skin and measured serum levels of PIIIP in ALS patients, and the results were compared with those of control subjects. RESULTS: Collagen bundles in the dermis of ALS were immunohistochemically strongly positive for PIIIP as compared with those of controls. The optical density of PIIIP immunostaining reactivity in ALS patients was significantly higher than in controls, and was significantly increased with duration of illness. Serum PIIIP levels in patients with ALS were significantly increased as compared with those in diseased control subjects and those in healthy control ones, and were positively and significantly associated with duration of illness. There was an appreciable positive correlation between concentrations of serum PIIIP and the density of PIIIP immunoreactivity of skin in ALS patients. CONCLUSION: These data suggest that a metabolic alteration of PIIIP may take place in the skin of ALS and the increased levels of serum PIIIP may reflect the increased PIIIP immunoreactivity of skin in ALS.

Activities of Daily Living↗