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Biomedical subjects

K Nozawa

Publications and source records attributed to K Nozawa.

At least 19 recordsLinked to original sources

Laminin-rich extracellular matrix maintains high level of hepatocyte nuclear factor 4 in rat hepatocyte culture.

Laminin-rich extracellular matrix, EHS-gel, has been demonstrated to keep a high level of liver-specific gene expression in cultured rat hepatocytes. To obtain information about the effect of EHS-gel on liver-specific functions, gene expression of liver-enriched transcription factors in rat hepatocytes was investigated. The apolipoprotein A-I and albumin mRNA levels were higher in hepatocytes cultured on EHS-gel than in those cultured on type I collagen (TIC). The levels of mRNA for HNF-4, C/EBP alpha and C/EBP beta were also higher on EHS-gel than on TIC. The level of HNF-4 mRNA in hepatocytes on EHS-gel was almost comparable to that in liver. The HNF-3 alpha mRNA level was lower on EHS-gel than on TIC. C/EBP beta mRNA was induced by dexamethasone in both EHS-gel and TIC. The induction of C/EBP alpha and HNF-4 by dexamethasone was observed only on TIC. These data suggest that EHS-gel leads hepatocytes to keep the phenotypic expression through high expression of liver-enriched transcription factors, such as HNF-4.

Animals

[CT of pulmonary dirofilariasis--differential diagnosis from lung cancer].

We present here four cases of pulmonary dirofilariasis in which histological examination of the surgical specimen showed occlusion of the peripheral pulmonary artery by filariae and formation of a necrotic mass surrounded by reactive inflammation and hemorrhage. Radiological examination showed a solitary pulmonary nodule in three cases and a wedge-shaped consolidation in one case. Although pulmonary nodules in dirofilariasis closely mimic bronchogenic carcinoma on radiographs , it is possible to distinguish them from bronchogenic carcinoma on the basis of the following findings: (1) coexistence of subtle satellite lesions, (2) absence of pleural involvement, (3) fine marginal speculations, and (4) lack of concentric marginal speculations (eccentric speculation). In each case of dirofilariasis, CT showed the peripheral pulmonary artery entering the mass. This finding differentiates this disease from metastatic lung tumor, because in tumor metastasis via the pulmonary arteries, visible vessels are not usually involved.

Aged

Isolation and structures of antibacterial binaphtho-alpha-pyrones, talaroderxines A and B, from Talaromyces derxii.

New compounds designated talaroderxines A (1) and B (2) were isolated from a new heterothallic ascomycetous fungus, Talaromyces derxii, cultivated on rice. The structures of 1a and 1b were elucidated by means of spectroscopic examination and chemical reactions. Talaroderxines A (1a) and B (1b) are atropisomers of a 6,6'-binaphtho-alpha-pyrone derivative, and have strong antibacterial activity against Bacillus subtilis.

Circular Dichroism

[Neo-adjuvant chemotherapy with tegafur suppository for rectal cancer--evaluation of the antitumor effects, tissue levels of 5-FU and inhibition of thymidylate synthase. Tochigi Colorectal Cancer Study Group].

We evaluated antitumor effect histologically and assayed the tissue levels of 5-fluorouracil (5-FU) and thymidylate synthase (TS) activity using surgical specimens obtained from the patients with rectal cancer, who were given tegafur suppositories prior to surgery. The antitumor effect was evaluated histologically according to classification of the general rules for the gastric cancer study (Japanese Research Society for Gastric Cancer). In 39 patients, 16 tumor specimens revealed no effect (grade-0), 22 tumors grade-1 effect, and one was not evaluable because of the severe inflammatory changes. In 23 of these patients, resected specimens were available for the assay. 5-FU levels in cancer tissues were significantly higher than those in normal tissues, and TS inhibition rates (TSIR) were almost identical, averaging around 20%, in both cancer and normal tissues. Comparing the 5-FU levels and TS activity according to the histological effects (i.e.: 'grade-0' vs 'grade-1'), the 5-FU levels in the tumors achieved grade-1 were significantly higher than in the tumors showed 'grade 0' (p less than 0.01), and TSIR in the former were relatively greater than in the latter (p = 0.053). It is suggested that both tissue levels of 5-FU and TSIR may be useful parameters to predict the anti-tumor effect against rectal cancer after administration of 5-FU and its derivatives.

Chemotherapy, Adjuvant

Orosomucoid typing of apes (family Pongidae) by isoelectric focusing: among primates do only humans have two functional orosomucoid loci?

It has been demonstrated that human orosomucoid (ORM) is controlled by more than one functional loci, while Macaca ORM is controlled by one locus. To examine the time when the ORM gene was duplicated in the evolution of primates, plasma samples from 118 apes (family Pongidae) belonging to 4 genera and 12 species were investigated for ORM polymorphism using isoelectric focusing followed by immunoprinting. The band patterns of ORM in the subfamily Ponginae showed quantitatively different products as in humans. A pedigree study of common chimpanzees supported the two-locus model for ORM. Gibbons (subfamily Hylobatinae) displayed highly variable band patterns, but the number of loci was not determined unequivocally. Thus, this study shows that duplication of the ORM gene in primates occurred either before or after the divergence of Hylobatinae and Ponginae, consistent with a previous prediction from the molecular evolutionary rate of ORM.

Alleles

Experimental acute poisoning in mice induced by emestrin, a new mycotoxin isolated from Emericella species.

The effects of emestrin (EMS), a secondary metabolite of the Emericella species, on male ICR mice were examined. The intraperitoneal LD50 values of EMS were 17.7 and 13.0 mg/kg at 24 and 48 hr, respectively. The target organs of EMS were the heart, liver and thymus. In doses over 30 mg/kg the experimental animals died from cardiac failure shortly after the injections. Several survivors that were given EMS in doses under 20 mg/kg showed severe centrilobular necrosis in the liver at 24 hr. Marked degeneration of mitochondria was seen in electron micrographs of both cardiac muscle cells and hepatocytes. In the degenerated hepatocytes, prominent proliferation of RER, membrane-limited inclusions containing both ribosome-like granules and RER, and fenestrated lamella-like structures were observed. Massive necrosis of lymphocytes was always observed in the cortical layer of the thymus of the survivors within 24 hr, while bilateral adrenalectomized mice showed no discernible pathomorphological changes in the lymphoid tissues. Pretreatment of mice with diethyl maleate increased the incidence and severity of hepatic necrosis, whereas that with either cysteine or CoCl2 reduced the severity of centrilobular necrosis of the liver. Pretreatment with phenobarbital had no significant effect on EMS-induced hepatic lesions.

Animals

Inhibition of lipoxygenase pathway reduces blood pressure in renovascular hypertensive rats.

To assess the potential role of the lipoxygenase (LO) pathway in the vasculature in an angiotensin II (ANG II)-dependent model of hypertension, we investigated the effect of LO pathway inhibition on blood pressure in the two-kidney, one-clip (2K,1C) Goldblatt hypertensive rat. The development of renovascular hypertension in 2K,1C rats was attenuated by oral administration of phenidone (Phe, 60 mg.kg-1.day-1), a nonselective LO inhibitor, throughout the 3 wk of observation after renal artery constriction. In contrast, the same treatment protocol had no effect on the evolution of hypertension in the deoxycorticosterone acetate-salt rat, which is considered to be an ANG II-independent form of hypertension. The hypotensive effect of Phe was not associated with changes in plasma renin or aldosterone concentration (PRC and PAC, respectively). In vitro synthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) by aortic segments was increased in 2K,1C hypertensive rats compared with sham-operated rats. In addition, the synthesis of 12-HETE was suppressed by the in vitro addition of Phe (10(-4) M) to aortic-segment incubates obtained from 2K,1C rats and sham-operated rats. Acute administration of Phe (30 or 60 mg/kg) in 2K,1C hypertensive rats produced a rapid and sustained decrease in mean blood pressure (MBP). This decrease in MBP was accompanied by a brisk rise in PRC and PAC. In contrast, bolus administration of indomethacin, a selective cyclooxygenase inhibitor, did not affect MBP, PRC, or PAC.(ABSTRACT TRUNCATED AT 250 WORDS)

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid

Structures of novel epipolythiodioxopiperazines, emethallicins B, C, and D, potent inhibitors of histamine release, from Emericella heterothallica.

Novel compounds designated emethallicins B (1), C (2), and D (3), along with emethallicin A (4), were isolated from the mycelium of the heterothallic fungus, Emericella heterothallica (mating type a). The structures of emethallicins B (1), C (2), and D (3) were determined on the basis of spectroscopic and chemical investigations. Emethallicins B (1) and C (2) are epitetrathiodioxopiperazines, which have the same basic carbon skeleton as apoaranotin (19) and acetylaranotin (17), respectively, whereas emethallicin D (3) is an epitrithiodioxopiperazine derivative, which has the same carbon skeleton as apoaranotin (19). It is very interesting that a large amount of the disulfide, emethallicin A (4), was isolated from the strain of mating type A and that the corresponding tetrasulfide, emethallicin B (1), and trisulfide, emethallicin D (3), were isolated from the other mating type strain, along with a small amount of the disulfide (4). Emethallicins B (1), C (2), and D (3) have potent inhibitory activity against compound 48/80-induced histamine release from mast cells, like emethallicin A (4).

Aspergillus

Hypotensive effects of the lipoxygenase inhibitor phenidone in two-kidney, one clip Goldblatt hypertension.

This study examined the role of the lipoxygenase (LO) pathway in the maintenance of hypertension in rats with two-kidney, one clip (2K,1C) Goldblatt hypertension. A single dose of the lipoxygenase blocker phenidone was injected intraperitoneally to 2K,1C rats during the early phase (14 days) of the development of hypertension (mean intraarterial blood pressure 137 +/- 3.9 mm Hg). Phenidone (60 mg/kg) markedly decreased arterial pressure to nadir levels of 58.9% of resting blood pressure. The maximal changes were observed 15 min after injection and the hypotensive response was sustained for at least 2 h. Plasma renin concentration (PRC) increased from 74.3 +/- 18.9 to 281.0 +/- 6.5 ng/mL/h after injection (P less than .05). Thus, the hypotensive effect of phenidone was not due to suppression of renin secretion but presumably due to inhibition of its effects. It is suggested that arachidonate metabolites of the LO pathway at the vascular bed may be involved in maintenance of high arterial pressure in 2K,1C renovascular hypertension in rat.

Animals

Selective inhibition of angiotensin II-mediated vasoconstriction by lipoxygenase blockade.

We have previously demonstrated that the lipoxygenase (LO) pathway has a specific role in the effect of angiotensin II (ANG II) on aldosterone secretion. To elucidate whether the LO pathway also participates in the vascular effects of ANG II, the nonselective LO inhibitor phenidone (PHE; 30 mg/kg) was administered to rats 1 h before graded dose ANG II infusion. PHE reduced the LO product 12-hydroxyeicosatetraenoic acid (12-HETE) in deendothelialized aortas by an average of 36% as determined by radiometric detection with high-performance liquid chromatography and radioimmunoassay methods. In parallel, the peak systolic pressor response to ANG II was lowered from 36.2 +/- 3.7 to 16.8 +/- 2.0 mmHg. The peak pressor responses to ANG II were also reduced by two other LO inhibitors, baicalein (30 mg/kg) and esculetin (60 mg/kg) (13.9 +/- 2.4 and 22.1 +/- 4.7 mmHg, respectively; P less than 0.01 compared with control rats for both), but not by the cyclooxygenase inhibitor indomethacin. The LO inhibitors baicalein (7.5 X 10(-5) M) and PHE (10(-4) M) markedly attenuated the in vitro contractile response to ANG II of femoral artery rings. In contrast, neither the in vivo nor in vitro constrictor responses to norepinephrine were affected by baicalein. Thus lipoxygenase blockade induces a direct and selective inhibition of ANG II-induced vasoconstriction. The LO pathway may have an important role in mediating the pressor effect of ANG II.

Angiotensin II

Isolation of a new tremorgenic indoloditerpene, 1'-O-acetylpaxilline, from Emericella striata and distribution of paxilline in Emericella spp.

The distribution of a tremorgenic mycotoxin, paxilline (1), was investigated in 19 species belonging to the genus Emericella. It was found that Emericella desertorum, E. foveolata, and E. striata produced paxilline (1). A new type of indoloditerpene, emindole DA (4), was also found in E. quadrilineata. A new tremorgenic indoloditerpene, 1'-O-acetylpaxilline (3), was isolated from the mycelium of E. striata. Its structure was established on the basis of spectroscopic investigations.

Acetylation

[Effects of acute hypoxia on cardiovascular dynamics, myocardial metabolism and ECG in dogs].

In pentobarbital-pancuronium anesthetized open chest dogs, left ventricular pressure (LVP), first derivative of LVP (dp/dt) and left ventricular end-diastolic pressure (LVEDP) were measured by a micromanometer tipped catheter, stroke volume and cardiac output (CO) by an electromagnetic flow meter and coronary sinus blood flow (CSBF), by a thermal dilution catheter, respectively. Mean arterial pressure (mAP), mean pulmonary arterial pressure (mPAP), lead II of ECG and esophageal temperature were monitored. Blood gas, catecholamines and lactate of arterial blood and coronary sinus blood were measured and myocardial lactate extraction ratio (MCL) was calculated. As an index of contraction, maximum positive dp/dt (+dp/dt max), and as an index of relaxation, the time constant (T) of isovolumic left ventricular pressure fall were employed, respectively. Acute hypoxia was induced by the inhalation of a 5% O2-95% N2 gas mixture and arterial blood oxygen pressure was maintained between 15 and 20 mmHg. Along with the advancement of hypoxia, +dp/dt max, CO and mAP gradually increased and peaked in 5 minutes. Thereafter, these parameters began to decrease and CO fell to zero in 20 minutes. mPAP and HR slowly increased and peaked in 9 and in 12 minutes, respectively. T was progressively prolonged throughout the hypoxia. CSBF/CO ratio was increased and stayed at a high level even after CO began to decrease. MCL decreased and changed from positive values to negative ones in 5 minutes. Epinephrine and norephinephrine concentrations slowly increased and peaked in 16 minutes. A gradual decrease in the R wave, shortening of the R-R interval and lengthening of the QTc interval were observed in ECG. This study indicated that the left ventricular relaxing function was impaired earlier than contracting function by acute hypoxia and that conversion of the augmented left ventricular contractile state to the depressed one coincided with conversion of myocardial lactate extraction to its production.

Acute Disease

Phylogenetic relationships among Japanese, rhesus, Formosan, and crab-eating monkeys, inferred from restriction-enzyme analysis of mitochondrial DNAs.

Mitochondrial DNA (mtDNA) polymorphisms in four species of macaques, i.e., Japanese monkey (Macaca fuscata), rhesus monkey (M. mulatta), Formosan monkey (M. cyclopis), and crab-eating monkey (M. fascicularis), were analyzed to study phylogenetic relationships. When 17 restriction enzymes of 6-bp recognition were used, 42-49 sites were observed in the samples. The estimated number of nucleotide substitutions per site among Japanese, rhesus, and Formosan monkeys ranges from 0.0318 to 0.0396, and that between the crab-eating monkey and the other monkeys from 0.0577 to 0.0653. These findings suggest that the crab-eating monkey diverged from the other three approximately 1.5-3.0 Myr before the present (Mybp) and that the Japanese, rhesus, and Formosan monkeys diverged approximately 0.9-1.8 Mybp, although the branching order cannot be determined conclusively.

Animals

A population-genetic study of crab-eating macaques (Macaca fascicularis) on the island of Angaur, Palau, Micronesia.

Blood protein polymorphisms of an introduced population of the crab-eating macaques on Angaur Island, Palau, Micronesia, were examined electrophoretically to assess genetic variability. Results showed a high degree of genetic heterozygosity and some distinctive features in the genetic constitution of this island population. Negative evidence is presented regarding ancestry from a single pair of macaques. Their origin is discussed in relation to the genetic structure of the present population.

Alleles