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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 451 records · Page 25Linked to original sources
PubMed1998

Structures and biosynthesis of aflastatins: novel inhibitors of aflatoxin production by Aspergillus parasiticus.

Two novel inhibitors of aflatoxin production by Aspergillus parasiticus were isolated from the mycelial extracts of Streptomyces sp. MRI142 and termed aflastatin A and B. The structures of aflastatin A (1) and B (5) were elucidated by NMR and chemical degradation experiments. These compounds have a novel skeleton of a tetramic acid derivative with a highly oxygenated long alkyl chain. The incorporation experiments using 13C-labeled acetates, propionate, glucose and glycolate suggested that most of the C2 and C3 units involved in the alkyl chain moiety of aflastatin A were biosynthesized from acetic and propionic acids, but five C2 units in the alkyl chain originated from glycolic acid.

Aflatoxins↗
PubMed1998

[Clinical assessment for the elderly with cancer].

It is necessary to assess a patient to undergo treatment for cancer from a variety of perspectives including physical function, function of cognition and activity and attitude to receive treatment. Chronological age alone is not a criterion for exclusion from major treatments because of individual differences. However, the age-related physical changes are most evident under major stress, such as surgery. Indices for physical assessment for detection of comorbidity, and for function of cognition and activity are shown here. Radiotherapy is still indicative for elderly cancer patients, because it is less aggressive than surgery, and very localized treatment compared to systemic chemotherapy, though it in itself is not an unaggressive treatment.

Activities of Daily Living↗
PubMed1998

[Pathophysiologic changes in patients with severe burns: role of hormones and chemical mediators].

The body's general response to serious thermal injury is characterized by increased vascular permeability immediately after injury and subsequent hypovolemic shock. Skeleto-muscular proteolysis, lipolysis, gluconeogenesis, increased metabolic rate, and a severe systemic inflammatory response induced by local infections or surgical procedures. The increased vascular permeability is mediated by histamine and numerous vasoactive substances, including serotonin, bradykinin, prostaglandins, leukotrienes, and platelet activating factor. Hyper-metabolism is mediated by hormones such as catecholamines, glucagon, and particularly cortisol. In addition, among the putative mediators of the metabolic response to injury, attention has recently been focused on cytokines and lipid mediators which are mainly produced by activated reticuloendothelial cells. Cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor and cortisol responses are interrelated, since cytokines activate the hypothalamo-adrenal axis. The cytokine storm seen in burn patients may be associated with depression of the immune system and with susceptibility to infection. Thermal injury can also lead to activation of the renin-angiotensin-aldosterone system, increased ADH production, and production of atrial natriuretic polypeptide to maintain the circulatory volume. Burn wound infections or surgical procedures can produce and perpetuate a mediator-induced systemic inflammatory response that may lead to multiple organ failure. Serum levels of interleukin-6 are very sensitive to surgical stress, and may be a useful indicator of the general condition of severely burned patients.

Burns↗
PubMed1998

[Relationship between maximum walking distance and frequency of outings in patients receiving home oxygen therapy].

We studied relationships between maximal walking distance (WDmax) and frequency of both outing enumerated by the aim of each outing as well as by each outing per se in patients receiving home oxygen therapy (n = 109). The results were compared with those from members of a seniors' club (n = 434). A questionnaire was used to obtain WDmax, defined as the distance a subject could walk without rest on level ground. In the questionnaire, WDmax was classified into five groups including 50 m (the distance between two electric posts), 500 m, 1 km, 1.5 km and more than 1.5 km. Since few patients could walk 1.5 km or more, they were included into the "can walk 1 km or more group". Outing frequency was measured using a 4-week diary which showed eight aims of outings including shopping, seeing a doctor, visiting friends or relatives, doing a hobby practicing something, participating in a seniors' club and neighborhood meetings or events, traveling, work and others. The subjects checked the diary each time they went out. True outing frequency was defined as the number of outings. If a subject left home to shop and visited a friend on the way home, the outing frequency enumerated by aims was two, while the true outing frequency was one. The mean and SE (1/4 weeks/one subject) of true outing frequency for patients (21.4 +/- 2.2) was significantly less than that of seniors' club members (45.6 +/- 1.4). Even in patients with a WDmax of 1 km or more, the frequency of travel was significantly lower than in seniors' club members. Although outing frequencies for shopping, seeing friends or relatives, doing a hobby and work were not significantly different between the two groups at a WDmax of 1 km or more, the outing frequency for work of patients was significantly lower at a WDmax of 500 m, and outing frequencies for the remaining three aims became significantly lower at a WDmax of 50 m. We demonstrated that in patients receiving home oxygen therapy, outing frequency was limited. A new modality is necessary to increase the outing frequency and to improve the quality of life for these patients.

Aged↗
PubMed1998

[An autopsy case of rigid spine syndrome].

We reported an autopsy case of rigid spine syndrome. A 20-year-old woman developed severe respiratory failure despite well-preserved muscle strength in her extremities. Although she had mechanical ventilation during sleep, she had normal arterial blood gas values during daytime. She was found dead in a morning approximately 71/2 years after the onset of the respiratory symptoms. At autopsy, the respiratory diaphragm and intercostal muscles, and the truncal paravertebral and sternocleidomastoid muscles were more significantly affected than the limb muscles. Many corpora amylacea were found in the whole spinal cord, though the significance remains to be elucidated.

Adult↗
PubMed1998

[High uptake on 11C methionine PET scan in the pituitary gland of a patient with cerebral glioma after surgical abortion].

Positron emission tomography (PET) with various tracers provides physiologic and biochemical information of living organs. Since radiologic examinations are usually avoided in pregnant women, mainly because of the radiation risk to the fetus, little is known about the effect of pregnancy on cerebral blood flow and metabolism. This paper reports findings of a 11C methionine PET scan of the pituitary gland in a woman after an abortion. The patient was a 31-year-old woman who suffered a seizure in the 9th week of her second pregnancy. On admission, computed tomography showed an abnormal mass lesion in the right frontal lobe, and a brain tumor was suspected. The patient and her family asked that that pregnancy be terminated. Seven days after a surgical abortion, methionine PET was performed. The scan showed high methionine uptake in the pituitary gland as well as in the right frontal lobe tumor. We suspected that another tumor was present in the pituitary gland. The right frontal tumor was partially resected, and pathologic examination of the resected specimen showed an astrocytoma (grade 2). After the operation, the patient received 50 Gy irradiation and chemotherapy. Two months after the operation, we performed a second methionine PET scan, which showed high uptake in the residual right frontal tumor but not in the pituitary gland. Results of other radiologic studies of the pituitary gland were normal. These findings suggest that the transport of 11C methionine into the pituitary gland may increase during pregnancy. Moreover, the pituitary gland of pregnancy should be a part of the differential diagnosis of pituitary adenomas in PET scanning. The change in physiologic uptake by the female pituitary gland should be taken into account in the diagnosis of pituitary adenoma with methionine PET.

Abortion, Therapeutic↗
PubMed1998

An initial study of the relationship between platelet adenylyl cyclase activity and alcohol use disorder criteria.

Low platelet adenylyl cyclase (AC) activity has been previously proposed to be a trait marker reflecting a genetic predisposition to alcohol dependence. To determine whether low platelet AC activity in alcohol-dependent subjects may be related to specific diagnostic criteria of DSM-IV and ICD-10 alcohol use disorders, we analyzed responses obtained in structured clinical interviews of 36 subjects who were determined to be alcohol-dependent Platelet AC activity when stimulated by guanylyl-imidodiphosphate [Gpp(NH)p] or forskolin was significantly lower in alcohol-dependent subjects as a group, compared with controls. When we analyzed the responses of the alcohol-dependent subjects to questions used to establish the diagnosis of alcohol abuse/dependence and dichotomized the subjects by positive or negative responses, we found that Gpp(NH)p- and forskolin-stimulated platelet AC activities were significantly lower among those alcohol-dependent subjects who had positive responses to questions related to drinking despite negative effects on mood ("Did you ever continue to drink even though you knew it was making you feel depressed, uninterested in things, or suspicious or distrustful of other people?"), drinking despite negative effects on health ("Did you ever continue to drink even though you knew it was causing you a health problem or making a health problem worse?"), or violence when drinking ("Did you get into physical fights while drinking or right after drinking?"). The alcohol-dependent subjects who had negative responses to these questions exhibited Gpp(NH)p- and forskolin-stimulated platelet AC activity that did not differ significantly from values in control subjects. The DSM-IV diagnosis of antisocial personality disorder did not distinguish alcohol-dependent subjects with regard to platelet AC activity. Gpp(NH)p and forskolin-stimulated AC activity may distinguish certain subtypes of alcoholics (i.e., those who develop negative mood in response to drinking, those who continue drinking despite health effects, and those who become violent while drinking).

Adenylyl Cyclases↗
PubMed1998

The mechanisms of hepatic sinusoidal endothelial cell regeneration: a possible communication system associated with vascular endothelial growth factor in liver cells.

Vascular endothelial growth factor (VEGF) has been shown to induce proliferation of sinusoidal endothelial cells in primary culture. To elucidate the mechanisms of sinusoidal endothelial cell regeneration in vivo, mRNA expression of VEGF and its receptors, flt-1 and KDR/flk-1, were studied in rat livers. Northern blot analysis revealed that VEGF-mRNA was expressed in hepatocytes immediately after isolation from normal rats. In contrast, non-parenchymal cells, including sinusoidal endothelial cells, expressed VEGF receptor-mRNA. Vascular endothelial growth factor-mRNA expression in hepatocytes was decreased during primary culture, but increased following a peak of DNA synthesis, induced by addition of epidermal growth factor or hepatocyte growth factor to the culture medium at 24 h of plating. In a 70% resected rat liver, VEGF-mRNA expression increased with a peak at 72 h after the operation, and mRNA expression of VEGF receptors between 72 and 168 h. In such a liver, mitosis was maximal in hepatocytes at 36 h and in sinusoidal endothelial cells at 96 h. Also, mRNA expression of both VEGF and its receptors was significantly increased in carbon tetrachloride-intoxicated rat liver compared with normal rat liver. Vascular endothelial growth factor expression was minimal in Kupffer cells isolated from normal rats, but marked in activated Kupffer cells and hepatic macrophages from the intoxicated rats. Vascular endothelial growth factor-mRNA expression was also increased in activated stellate cells from these rats and in the cells activated during primary culture compared with quiescent cells. We conclude that increased levels of VEGF expression in regenerating hepatocytes may contribute to the proliferation of sinusoidal endothelial cells in partially resected rat liver, probably through VEGF receptors up-regulated on the cells. Also, VEGF derived from activated Kupffer cells, hepatic macrophages and stellate cells may be involved in this proliferation in injured rat liver.

Animals↗
PubMed1998

[Cell adhesion molecule].

Platelet aggregation and thrombus formation secondary to plaque disruption at the sites of coronary atheroma play a prominent role in the pathophysiology of acute coronary syndromes. A fundamental role of cell adhesion molecules are implicated for the disease process of these syndromes. These adhesion molecules play a active role in cell-extracellular matrix interaction and cell-cell interaction at the first step of the thrombus formation at the culprit lesion of the coronary artery. A more comprehensive understandings of adhesion molecules and their functions may promote the development of potentially more effective therapeutic strategies for the syndromes. This review focuses on the role of platelet glycoprotein Ib, IIb/IIIa and P-selectin in the thrombotic process.

Acute Disease↗
PubMed1998

[Comparison of antiemetic efficacy of granisetron as premedication versus combination therapy of granisetron].

In this study we compared two methods of granisetron administration. One method was via a drip infusion with 100 ml of normal saline 30 minutes prior to administration of CDDP (Group A). The other method was direct injection of granisetron into the CDDP containing bottle (Group B). By employing a randomized cross-over method, we evaluated the acute response (less than 24 hours) according to Furue's criteria in 34 patients. Each of the patients received more than two cycles of chemotherapy containing more than 50 mg of CDDP. In both arms of the study nausea, vomiting and anorexia showed no difference. Moreover, there was no evidence of toxicity due to granisetron. The overall response rate of granisetron to nausea was 84.4%. We conclude that granisetron is an effective drug as an antiemetic, and the direct injection of granisetron into the CDDP containing bottle has the same effect when compared to the normal method of administration, together with an equivalent safety profile.

Aged↗
PubMed1998

[Fulminant hepatic failure related to immunosuppressive therapy in an asymptomatic HBsAg carrier with idiopathic interstitial pneumonia].

A 72-year-old woman who was an asymptomatic HBsAg carrier was admitted because of productive cough and dyspnea on exertion. After close examination, she was given a diagnosis of idiopathic interstitial pneumonia (IIP), and treated with glucocorticoids and cyclophosphamide. However, fulminant hepatitis type B developed and the patient died of respiratory complications stemming from the acute exacerbation of IIP. To avoid such outcomes, extra caution should be taken when planning immunosuppressive therapy for HBsAg carriers.

Aged↗
PubMed1997

Exchangeability of the b subunit of the Cl(-)-translocating ATPase of Acetabularia acetabulum with the beta subunit of E. coli F1-ATPase: construction of the chimeric beta subunits and complementation studies.

The gene encoding the b subunit of the Cl(-)-translocating ATPase (aclB) was isolated from total RNA and poly(A)+ RNA of Acetabularia acetabulum and sequenced (total nucleotides of 3038 bp and an open reading frame with 478 amino acids). The deduced amino acid sequence showed high similarity to the beta subunit of the F type ATPases, but was different in the N-terminal 120 amino acids. The role of the N-terminal region was investigated using an F -ATPase beta-less mutant of E. coli, JP17. The JP17 strain expressing the aclB could not grow under conditions permitting oxidative phosphorylation, although ACLB was detected in the membrane fraction. The beta subunit was divided into three portions: amino acid position from 1 to 95 (portion A), 96 to 161 (portion B) and 162 to the C-terminus (portion C). The corresponding regions of ACLB were designated as portions A' (from 1 to 106), B' (from 107 to 172) and C' (from 173 to 478). Chimeric proteins with combinations of A-B'-C', A-B-C' and A'-B-C restored the function as the beta subunit in E. coli F0F1-complex, but those with combinations of A'-B'-C and A-B'-C had no function as the beta subunit. These findings suggested that portion B plays an important role in the assembly and function of the beta subunit in the F0F1-complex, while portion B' of ACLB exhibited inhibitory effects on assembly and function. In addition, portion A was also important for interaction of the beta subunit with the alpha subunit in E. coli F0F1-complex. These findings also suggested that the b subunit of the Cl(-)-translocating ATPase of A. acetabulum has a different function in the Cl(-)-translocating ATPase complex, although the primary structure resembled to the beta subunit of the F1-ATPase.

Acetabularia↗
PubMed1997

High levels of expression and nuclear localization of interleukin-1 beta converting enzyme (ICE) and CPP32 in favorable human neuroblastomas.

Neuroblastomas frequently show spontaneous regression and differentiation, which may at least partly be regulated by signaling through nerve growth factor and its receptors, TRK-A and p75LNTR. We studied 52 neuroblastic tumors to test whether the cell death-related proteases, interleukin-1 beta converting enzyme (ICE), CPP32, and Ich-1, were involved in the regression of the tumors. High levels of expression of ICE and CPP32 were significantly correlated with a high level of TRK-A expression, single copy of N-myc, younger age, lower stages, and better prognosis. The immunohistochemical studies and Western analyses as well as the terminal dUTP-biotin nick end labeling (TUNEL) method revealed that both ICE and CPP32 were translocated from the cytoplasm into the nuclei in regressing, apoptotic tumor cells. Our results suggest that ICE and CPP32 cysteine proteases may play an important role in regulating the apoptotic process of the favorable neuroblastomas.

Age Factors↗
PubMed1997

Interaction of the DNA topoisomerase II catalytic inhibitor meso-2,3-bis(3,5-dioxopiperazine-1-yl)butane (ICRF-193), a bisdioxopiperazine derivative, with the conserved region(s) of eukaryotic but not prokaryotic enzyme.

ICRF-193 [meso-2,3-bis(3,5-dioxopiperazine-1-yl)butane], a bisdioxopiperazine compound, has been shown to be a catalytic inhibitor of DNA topoisomerase II by stabilizing the enzyme in the form of a closed "protein clamp," an intermediate form in the catalytic cycle (Roca et al., Proc Natl Acad Sci USA 91: 1781-1785, 1994). In view of its usefulness as a probe in the functional analysis of the enzyme, we tried further to define the domain(s) of the enzyme interacting with the drug by examining its inhibitory activity on type II topoisomerases from various species of eukaryotes and prokaryotes. ICRF-193 inhibited the enzyme from yeast, fly, frog, plant, and mammals at IC50 values in the range of 1-13 microM. Experiments using fission yeast truncated mutant type II enzyme lacking both amino-terminal 74 amino acids and carboxy-terminal 265 amino acids revealed that ICRF-193 interacts with the 125 kDa "core" polypeptide of the enzyme. In contrast, prokaryotic type II enzymes, Escherichia coli DNA gyrase, topo IV, and phage T4 topo, were not affected by the drug. From these results, the domain(s) common to eukaryotic but not to prokaryotic type II enzymes interacting with ICRF-193 was speculated.

Amino Acid Sequence↗
PubMed1997

Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae.

DNA double-strand breaks are repaired by homologous recombination or DNA end-joining, but the latter process often causes legitimate recombination and chromosome rearrangements. One of the factors involved in the end-joining process is Hdf1, a yeast homologue of Ku protein. We used the yeast two-hybrid assay to show that Hdf1 interacts with Sir4, which is involved in transcriptional silencing at telomeres and HM loci. Analyses of sir4 mutants showed that Sir4 is required for deletion by illegitimate recombination and DNA end-joining in the pathway involving Hdf1. Sir2 and Sir3, but not Sir1, were also found to participate in these processes. Furthermore, mutations of the SIR2, SIR3 and SIR4 genes conferred increased sensitivity to gamma-radiation in a genetic background with a mutation of the RAD52 gene, which is essential for double-strand break repair mediated by homologous recombination. These results indicate that Sir proteins are involved in double-strand break repair mediated by end-joining. We propose that Sir proteins act with Hdf1 to alter broken DNA ends to create an inactivated chromatin structure that is essential for the rejoining of DNA ends.

DNA Repair↗