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Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 901 records · Page 50Linked to original sources

Regulation of scu-PA secretion and u-PA receptor expression in osteoblast-like cells.

The production of proteolytic enzymes by osteoblasts is considered important for initiating osteoclastic bone resorption. Using the established cell line NY as an example of osteoblast-like cells, the effect of intracellular cyclic AMP (cAMP) and protein kinase C (PKC) on plasminogen activator secretion and its specific binding to the cells were investigated. HT-1080 cells were used as the control. NY cells predominantly secrete single-chain urokinase-type plasminogen activator (scu-PA) and some two-chain u-PA. Both scu-PA and u-PA were present in the cell surface and cell lysate of NY cells, and their distribution in HT-1080 cells was quite similar to that of NY cells. Exposing cells to phorbol myristate acetate (PMA) or dibutyryl cyclic AMP (db cAMP) enhanced the secretion of scu-PA and two-chain u-PA, whereas 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) decreased scu-PA secretion, indicating that it is enhanced by protein kinase C (PKC) as well as by cAMP in NY cells. On the other hand, in HT-1080 cells, PMA decreased the level of two-chain u-PA secretion into the conditioned medium. The binding assay of 125I-DFP-u-PA to NY cells revealed the presence of a single class of binding sites with a Kd of 2.23 nM and Bmax of 0.82 x 10(6) binding sites/cell. PMA however, altered neither the Kd nor the Bmax. Dibutyryl cAMP increased the Bmax 1.9 fold. Thus, NY cells secrete u-PA and express specific binding sites on the cell surface, which are modulated by cAMP and PKC.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic AMP↗

Morphogenesis of compound melanosomes in melanoma cells of a gray horse.

A thoroughbred horse, gelding, gray color, aged 19 years old had cutaneous melanomas from the root to the middle of the tail, and throughout the connective tissues of the whole body. Histologically, the tumors were diagnosed as mature melanotic melanomas characteristically deposited with abundant melanin pigment. Examined with an electron microscope, melanosomes were electron opaque without internal structure (stage IV), or as mature granular and lamellar types. Most of them were fused with each other, and formed compound melanosomes, which was similar to internal melanin aggregates in shape. The internal melanin aggregates gradually disintegrated, and compound melanosomes grew spherical. The compound melanosomes changed into autophagosomes.

Animals↗

[Nutritional assessment and rapid turnover protein in the elderly].

Nutritional assessment with respect to rapid turnover protein (RTP) in the elderly was performed in 22 outpatients (7 males and 15 females, mean age 77 years) who suffered from slight illnesses such as mild hypertension and osteoporosis. Their nutritional parameters were almost within the normal range, judging from body mass index (BMI) and their plasma levels of total protein, albumin, lipids and RTP (transferrin, pre-albumin and retinol-binding protein). Statistically, BMI had a significantly positive correlation with subcutaneous fats and total protein and had a significantly negative correlation with HDL-cholesterol. Retinol-binding protein had a significantly positive correlation with prealbumin, ferritin and vitamin A. Conversely, in 12 bedridden patients the nutritional status was very poor, with their plasma levels of the above markers being significantly lower than those of the controls. We administered an enteral diet (EWH330) to 10 bedridden patients in an effort to restore their nutritional status. As a result, their nutritional parameters, especially RTP showed a significant increase after 4 and 8 weeks of the administration of EWH330. These results suggest that RTP is a very sensitive parameter of nutritional assessment in the elderly.

Aged↗

Synthesis and properties of oligolysine and oligoglutamic acid derivatives containing nucleosides.

Nucleic acid analogs of L-lysine derivatives containing uridine and/or adenosine were synthesized. As dimer models, Lys(Urd)-Lys(Urd) and Lys(Urd)-Lys(Ado) were prepared by activated ester method. These dimers were found to form complex with poly(A), which was observed from hypochromicity of UV spectra. Furthermore, glutamic acid derivatives containing uridine and adenosine were also prepared. Oligomerization of glutamic acid derivatives were studied by Merrifield's solid phase synthesis.

Molecular Structure↗

[Examination of serum prostate specific antigen (PSA) in the mass screening for prostatic diseases].

While it is widely recognized that elevated prostate specific antigen (PSA) correlates with the presence of prostate cancer, little data exist on the use of PSA as the initial test in the mass screening for prostate diseases. Thus, digital rectal examination, transrectal ultrasonography of the prostate as well as measurements of serum PSA were performed in a series of 647 men 55 years old or older who participated in the mass screening. We found 7 patients with prostatic cancer (1.1%) and 53 with benign prostatic hypertrophy faced with the necessity of the therapy (8.2%). The PSA values of 6 cancer patients exceeded 3.6 ng/ml and that of one cancer patient was 2.6 ng/ml. While 587 subjects were judged to be without clinical evidence of prostate cancer and benign prostatic hypertrophy, 564 of them has PSA values under 2.6 ng/ml. The proportion of those who were free from prostatic diseases and had a PSA value of 2.6 ng/ml or more was only 3.4% of all participants. Since the proportion of the subjects falsely screened at a relatively lower cut-off point of PSA was quite low, the measurement of serum PSA is suggested to be useful as the initial test in the mass screening for prostatic diseases.

Aged↗

[Effect of training fitness on obesity, hypertension, hyperlipidemia and disorders in glucose metabolism].

Effects of physical training on obesity, hypertension, hyperlipidemia and disorders of glucose metabolism were investigated in 359 males, 30-59 years of age. Body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and fructosamine (FA) were measured before and after the 2 month period of physical training at intensities of about 50% of maximal O2 uptake. Results are summarized as follows; 1. Means of BMI, SBP, DBP, TC and FA after the training were significantly lower than before the training. Mean of HDL-C was significantly higher than before the training. 2. In subjects with high BMI (n = 124), high SBP (n = 129) and high DBP (n = 128), means of BMI, SBP and DBP decreased with increase of training time per week. In subjects with low HDL-C (n = 104), high TC (n = 135) and high FA (n = 66), changes in means of TC, HDL-C and FA after the training did not show a relationship to training time per week. 3. Differences observed for measured values before and after the training of 2-3 hours per week were 0.4 kg/m2 in BMI, 15 mmHg in SBP and 10 mmHg in DBP, suggesting that training of 2-3 hours per week was effective in intervention of obesity and hypertension.

Adult↗

[Cognitive ability regarding dental plaque and oral bacteria in schoolchildren: results from an interview research of primary and junior high school students].

The cognitive abilities regarding dental health terms, especially of dental plaque, were examined among schoolchildren. An interview of 112 primary and junior high school students was performed to test knowledge of the cause of dental caries and meaning of some dental health terms. Results indicate that most schoolchildren had difficulty understanding the correct meaning of dental plaque and oral bacteria. Some of them did not recognize the existence of oral bacteria, much less dental plaque. From these results, factors which may interfere with correct understanding of dental plaque were examined. Among them, inaccurate knowledge of existence of oral bacteria appears to be an important factor.

Adolescent↗

[A case of sleep apnea syndrome with significant alteration of apnea index by sleep position].

An obese 37-year-old man (130% ideal body weight) was admitted to our hospital with the complaint of excessive daytime sleepiness. During all-night polysomnography, he showed predominantly obstructive sleep apnea and an apnea index (AI) of 57.5, and was diagnosed as having obstructive sleep apnea syndrome (OSAS). However, AI values calculated separately for the time in the supine position (AI-S) and in the lateral decubitus position (AI-L) were 82.4 and 5.9, respectively. Moreover, duration of apnea, lowest SaO2, and the quality of sleep were improved when sleeping in the lateral compared to the supine position. After weight reduction of 7 kg, AI in total decreased to 33.2, although AI-S was 77.3 and AI-L was 3.8. The improvement of AI in total to be due to a relative increase during sleep in the lateral position. These results suggest that in some OSAS patients, the sleep position should be taken into account in assessing the severity of the disease or in evaluating the effects of therapy. This study also suggests the efficacy of sleep position adjustment in the treatment of OSAS.

Adult↗

[Toxicological findings in a death involving hydrogen sulfide].

A case of fatal hydrogen sulfide poisoning in a sewage disposal plant is described. Hydrogen sulfide levels were determined in several postmortem body tissues and fluids using gas chromatography with a flame photometric detection (GC-FPD). The concentrations of hydrogen sulfide in the blood, muscle, liver, lung, kidney, heart and brain were 0.305, 0.690, 1.089, 1.338, 1.170, 1.366 and 0.875 (micrograms/g or ml), respectively. The results are discussed in the light of the existing literature on the toxicological significance of hydrogen sulfide concentrations.

Adult↗

[A case report of aneurysm of the diverticulum of the ductus arteriosus].

A 59-year-old man who was admitted with hoarseness and diagnosed as aneurysm of the diverticulum of the ductus arteriosus was reported. In our case, enhanced computed tomography and aortography gave reliable informations. Operation was performed through a posterolateral thoracotomy under partial cardiopulmonary bypass. The aneurysm was successfully resected and defect of the aortic wall was covered with Dacron patch. Postoperative course was uneventful. To our knowledge, this is 12th surgically treated case in Japan.

Aneurysm↗

[Effect of high-dose thiazide treatment and low-K diet on citrate uptake by rat renal brush border membrane vesicles (BBMV)].

In order to study the effect of high-dose thiazide treatment and low-K diet on citrate uptake by rat renal brush border membrane, we measured citrate uptake by rat renal brush border membrane vesicles (BBMV) and analyzed the acid-base balance of non-treated rats, high-dose thiazide-treated rats and low-K diet rats. Seven-week male Wistar rats (Jcl) were housed in metabolic cages, given 10 mg/Kg BW/day hydrochlorothiazide (HCTZ) by a gastric tube once a day for 3 weeks (high-dose thiazide treated rats) or a low-K diet for 3 weeks (low-K diet rats). Arterial blood was taken from the aorta and BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by a Millipore rapid membrane filtration technique. High-dose thiazide treatment for 3 weeks showed a significant metabolic alkalosis and increase of urinary citrate excretion. However, it had no significant effect on citrate uptake by BBMV. On the other hand, low-K diet for 3 weeks showed significant hypokalemia, metabolic alkalosis and decrease in urinary citrate excretion. Moreover, it increased the maximal activity (Vmax) with no difference in citrate affinity (Km). These data suggested that urinary citrate excretion was more affected by the K depletion than by the acid-base balance.

Animals↗

Stemline heterogeneity of nuclear DNA in hepatocellular carcinoma.

Flow cytometric analysis of intratumoral DNA stemline heterogeneity was carried out in 48 patients who underwent liver resection for hepatocellular carcinoma (HCC). The nuclear DNA content was determined in specimens cut into one centimeter square pieces; all specimens had been taken from the largest section of the tumor. Of the 48 tumors twelve (25%) were diploid (group D), 11 (22.9%) had both diploid and aneuploid patterns (group DA), and the remaining 25 (52.1%) were aneuploid (group A). Out of 25 group A tumors, eleven had two or more different aneuploid peaks (multiple aneuploid). Thus, DNA stemline heterogeneity was present in 22 tumors (45.7%). With respect to survival, patients with group A tumors had a significantly poorer prognosis than did those with group D tumors, irrespective of tumor size. In group DA patients, the outcome was influenced by the "poor" prognostic nature of the positive DNA aneuploidy. Thus, HCC has a higher incidence of intratumoral DNA heterogeneity than previously considered, and the prognosis for patients with a positive aneuploidy pattern is poor.

Adult↗

[Biochemical modulation of chemotherapy of urologic malignancies].

Generally speaking, the outcome of cancer chemotherapy for urologic malignancies is poor. This poor response is attributed to the weak sensitivity to anti-cancer agents, represented by renal cell cancer, and the advanced age of most patients to tolerate the toxicities of the drugs, as is experienced in prostate cancer patients, which leads to insufficient therapy. Biochemical modulation was initially used to refer to the enhancement of the effect of 5-FU by modulating its pharmacological action by the addition of other drugs. The concept was expanded to the enhancement of the effect of the chemotherapeutic agents, potentiating the pharmacological action and/or reducing the toxicity, by means of any drug or biological modality. This preface is for the following 7 articles which were based on the presentations at the Symposium of 42nd Annual Meeting of Central Section of Japanese Urological Association in 1992, entitled as "Biochemical modulation of chemotherapy of urologic malignancies".

Antineoplastic Combined Chemotherapy Protocols↗

[The enhancement of the chemotherapeutic effects on human prostate cancer cell--the combination with the growth factor interaction inhibitor (suramin)].

The present study was designed to evaluate the antiproliferative effects of suramin and the combination of suramin plus cisplatin (CDDP) on the hormone-independent human prostate carcinoma cell line (PC-93). In vitro, suramin induced a dose-dependent reduction of PC-93 proliferation, and at the clinically achievable concentration (300 micrograms/ml), suramin induced a 19.7% decrease in proliferation on the 3rd day compared to suramin-free control (P < 0.01). However, from the 4th day on the inhibitory action of suramin was reversed following exposure. The suramin-cisplatin combination showed an additive effect (inhibition ratio 32.4% on the 3rd day), and prolongation of the inhibition activity on the 4th day on, but it did not show any synergistic effect. Suramin inhibited dose-dependently the growth stimulatory effect of exogenous epidermal growth factor (EGF). In vivo study, suramin and suramin-cisplatin combination showed antitumor effects continuously in nude mouse implanted PC-93. These findings suggest that the inhibitory effects of suramin on PC-93 are mediated by inhibition of the EGF-mediated growth mechanism, but by a cytostatic rather than cytotoxic manner in vitro. In addition, other mechanisms such as inhibition of angiogenesis factor might exist in vivo.

Animals↗