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Biomedical subjects

M Fukumoto

Publications and source records attributed to M Fukumoto.

At least 73 records · Page 4Linked to original sources
PubMed1998

Predomination of Dimers over Naturally Occurring Anthraquinones in Soil

Four bianthraquinones and two monoanthraquinones were isolated as the major soil anthraquinones from a volcanic ash soil in Japan. They were identified as a new natural product 5,5'-biphyscion (named hinakurin) (3) and five known compounds, chrysotalunin (1), (-)-7,7'-biphyscion (2), microcarpin (4), chrysophanol (5), and physcion (6) using MS, 1D NMR, and 2D NMR techniques. Although the dimers (1-4) are rarely found as natural products, they, along with 5 and 6, were ubiquitous and predominant over other anthraquinones in various soils from Japan and Nepal.

Journal Article↗
PubMed1998

Transcript levels of aquaporin 1 and carbonic anhydrase IV as predictive indicators for prognosis of renal cell carcinoma patients after nephrectomy.

Since failure of differentiation has been suggested to be involved in the neoplastic process and progression of tumors, we evaluated whether the transcript levels of differentiation markers of proximal renal tubular cells, from which renal cell carcinoma (RCC) arises, could be used as prognostic markers. We used Northern blot analysis to study the expression of aquaporin 1 (aqp1) and carbonic anhydrase IV (ca4) genes in 66 paired samples of primary RCC and non-tumorous kidney tissues. Poor differentiation of tumor cells and non-clear cell-subtype RCC were significantly associated with low levels of aqp1 transcripts. When patients were divided into 2 groups according to level of aqpI transcript in RCC, a low level of aqp1 was significantly associated with unfavorable outcome. Among 18 patients with metastatic RCC and 40 patients with moderately differentiated RCC, those with RCC expressing low levels of aqpl mRNA demonstrated poorer survival than those with RCC expressing relatively high levels of aqp1. Similarly, decreased expression of ca4 mRNA in RCC was associated with poor survival. On multivariate analysis, transcript levels of aqpI and stage of the tumor were the independent factors predicting disease-specific survival. Transcript levels of aqp1 may serve as a new molecular prognostic marker in patients with RCC following nephrectomy.

Aquaporin 1↗
PubMed1998

Dual-isotope SPECT diagnosis of a skull-base metastasis causing isolated unilateral hypoglossal nerve palsy.

We describe a 48-year-old female with an isolated unilateral hypoglossal nerve palsy caused by a skull base metastasis from breast cancer. The patient had a medical history of conservative breast therapy for breast cancer. Although the cause of such a neurological deficit includes various pathologies, the reports focusing on metastatic tumor have been limited in number. Radiologic investigation showed a mass involving both the right hypoglossal canal and the clival edge. Swelling of the hypoglossal nerve was observed in views including its canal. Three-dimensional CT images demonstrated the tumor protruding from the enlarged external orifice of the hypoglossal canal. In the present report we mentioned a nuclear medicine procedure to visualize and characterize the small, abnormal tissue in the skull base. Dual-isotope SPECT confirmed an abnormal uptake of 99mTc-HMDP around the hypoglossal canal and a 201Tl-positive elongated lesion running along the hypoglossal nerve.

Cranial Nerve Diseases↗
PubMed1998

Membrane-type matrix metalloproteinase-1(MT1-MTP) gene is overexpressed in highly invasive hepatocellular carcinomas.

BACKGROUND/AIMS: The matrix metalloproteinase (MMP) family play important roles in the invasion of cancer cells by degrading the extracellular matrices. The current study was designed to determine the expression pattern of membrane-type matrix metalloproteinase-1 (MT1-MMP) in hepatocellular carcinomas and its participation in invasion potential. METHODS: MT1-MMP mRNA expression was examined in 25 human hepatocellular carcinoma specimens using Northern blot, and the correlation to clinicopathological features was evaluated. In situ hybridization and immunohistochemistry were performed to study the localization and the cells responsible for the production. RESULTS: Northern blot analysis revealed high levels of MT1-MMP mRNA expression in tumorous portions in all cases, whereas in non-tumorous portions moderate or faint expression was evident in 22/25 cases. In 21/25 cases, the expression levels in tumorous portion were higher than those in non-tumorous portion. In particular, hepatocellular carcinoma with capsule infiltration demonstrated significantly higher expression than those without (p<0.05). In situ hybridization and immunohistochemical study revealed MT1-MMP transcripts and proteins in cancer cells and stromal cells, respectively. MT1-MMP positive cells were preferentially observed in the invading border of tumor nests. The MMP-2 transcript showed a similar pattern to that of MT1-MMP by in situ hybridization. CONCLUSION: The present study showed that the MT1-MMP gene is strongly expressed in hepatocellular carcinoma cells and is involved in the invasion potential of hepatocellular carcinoma, and also that MT1-MMP may be one of the key molecules responsible for the invasion potential of hepatocellular carcinoma. Furthermore, the evidence suggests that MT1-MMP and MMP-2 cooperate in the process of cancer invasion.

Adult↗
PubMed1998

Heterogeneous distribution of K-ras-mutated epithelia in mucinous ovarian tumors with special reference to histopathology.

The carcinogenic process of epithelial ovarian carcinomas is still unknown, and both pathways of de novo carcinogenesis from the surface epithelium and malignant transformation of benign cystadenoma have been suggested. Especially in mucinous ovarian tumors, the transition from benign cystadenomas to tumors of low malignant potential (LMP) or carcinomas has been implicated. To elucidate this possibility, we analyzed the presence or absence of heterogeneity of the K-ras mutation corresponding to the histological heterogeneity in 71 epithelial ovarian tumors, including 31 mucinous tumors. K-ras mutation was identified in nine mucinous tumors (4 of 10 carcinomas, 4 of 14 LMP tumors, and 1 of 7 cystadenomas) and in two nonmucinous carcinomas. Microdissection of multiple sites with reference to their histological appearance showed the heterogeneous distribution of K-ras-mutated epithelia in two of the nine mucinous tumors. One mucinous carcinoma showed K-ras mutation in all of the histologically LMP and malignant portions, but not in benign portions. In another LMP tumor, all of the LMP portions and one of the benign portions showed K-ras mutation, whereas the other two benign portions had no mutation. In the remaining seven mucinous tumors with K-ras mutation, however, there was a homogeneous distribution of K-ras-mutated epithelia irrespective of their histological appearance. These findings suggest that the K-ras mutation occurs during the transformation from benign cystadenomas to LMP or malignant lesions, providing molecular genetic support for the hypothesis of the "adenoma-carcinoma sequence" in some mucinous ovarian tumors, but in other cases an alternative pathway may also be possible.

Adenocarcinoma, Mucinous↗
PubMed1998

Expression and distribution of brain natriuretic peptide in human right atria.

OBJECTIVES: We investigated expression of brain natriuretic peptide (BNP) as well as atrial natriuretic peptide (ANP) and their genes in human right atria. Their relations with atrial pressure were also examined. BACKGROUND: The BNP plays a roll in electrolyte-fluid homeostasis such as ANP. The tissue level is reported to be elevated in the failing ventricles. However, expression and transmural distribution of BNP in the atria remain unclear. METHODS: Expression of ANP and BNP was immunohistochemically investigated in the right atrial (RA) specimens from 21 patients who had undergone cardiac surgery. The mRNA of specimens were quantitatively measured by Northern blot analysis and also evaluated by in situ hybridization. In addition, plasma levels of ANP and BNP were measured in the patients. RESULTS: The BNP immunoreactivity was diffusely seen in RA tissue of patients with mean RA pressure (mRAP) of 5 mm Hg or more, but it was noted only in the subendocardial half of the atria of those with mRAP less than 5 mm Hg. There was a significant correlation between the incidence of BNP-positive myocytes and mRAP (r = 0.850, p < 0.0001). Conversely, ANP-positive myocytes were found diffusely in all cases. In Northern blot analysis, the mRNAs levels of ANP and BNP in the atrial tissue were positively correlated with the mRAP (ANP, p = 0.775, p < 0.005 and BNP, p = 0.771, p < 0.005). In situ hybridization confirmed these findings. The mRNA levels were significantly correlated to each other (r = 0.845, p < 0.0002). Plasma ANP and BNP levels were elevated in the patients compared with that in controls; however, none were significantly correlated with the mRAP. CONCLUSIONS: Expression of BNP and BNP mRNA is augmented in the atria with increased pressure, and distributed predominantly in the subendocardial side. The level of BNP mRNA was well correlated with that of ANP mRNA. Thus, these two genes might be commonly regulated in response to atrial pressure.

Aged↗
PubMed1998

Overexpression of the rhoC gene correlates with progression of ductal adenocarcinoma of the pancreas.

It has been reported that the rho genes, which consist of a ras-related small GTPase protein family, regulate cytoskeletal structures and have the potential to transform cultured cells. To investigate the biological relevance of the rho genes in pancreatic carcinogenesis, we examined expressions of the rhoA, B and C genes by polymerase chain reaction after reverse transcription (RT-PCR) in 33 cases of ductal adenocarcinoma of the pancreas. In addition, mutations of the K-ras, rhoA, B and C genes were studied in the same series of tumour tissues to correlate with rho gene expressions. The expression levels of the rhoC gene were significantly higher in tumours than in non-malignant portions (P < 0.001). Metastatic lesions overexpressed the rhoC gene compared with primary tumours (P < 0.05). Carcinoma tissues with perineural invasion and lymph node metastasis exhibited significantly higher expressions of the rhoC gene than tumours without these manifestations (P < 0.001 and P < 0.05 respectively). Overexpression of the rhoC gene significantly correlated with poorer prognosis of patients with pancreatic adenocarcinoma (P < 0.05). In contrast, the expression levels of the rhoA and B genes showed no significant relationship with clinicopathological findings. Mutation was not found either in the rhoA, B or C gene sequences examined. K-ras gene mutation, detected in 27 out of 33 (81.8%) cases, did not affect the expression levels in any of the rho genes. These suggest that elevated expression of the rhoC gene may be involved in the progression of pancreatic carcinoma independent of K-ras gene activation.

Adult↗
PubMed1998

Expression of class I human leukocyte antigen (HLA) and beta2-microglobulin is associated with decidualization of human endometrial stromal cells.

Human leukocyte antigen (HLA) class I molecules play a central role in the immune system through either presentation of endogenous antigen and activation of T lymphocytes or functional emergence of natural killer (NK) cells. Various types of immune cells are present in the human endometrium and are believed to be involved in reproductive function and/or immunological reaction. However, little is known about the expression status and function of HLA class I molecules in the human endometrium. We therefore examined mRNA expression of HLA class I. In addition, we analysed gene expression and localization of beta2-microglobulin (beta2-MG), which is the non-variant chain of all HLA class I molecules. Compared with non-decidualized tissues, mRNA expression of both HLA class I and beta2-MG was significantly higher in decidualized endometria in the late secretory phase, under progestin treatment and during early pregnancy. Immunohistochemical studies revealed that beta2-MG was localized in decidualized endometrial stromal cells, indicating that the distribution of beta2-MG is topologically correlated with that of CD56bright+ NK cells. In-vitro culture of human endometrial stromal cells demonstrated that HLA class I mRNA was induced during the decidualization by progesterone. Accordingly, the expression of HLA class I molecules is transcriptionally activated along with decidualization of human endometrial stromal cells, and may represent an immuno-endocrine function of the endometrium.

Adult↗
PubMed1998

Dual isotope SPECT in malignant Jacod's syndrome.

A case is presented of metastatic tumor causing Jacod's syndrome: total ophthalmoplegia, blindness, and trigeminal neuralgia. Abnormal soft tissue invading the orbital apex, anterior clinoid process, and cavernous sinus was difficult to assess by CT and MRI, but dual-isotope SPECT including Tc-99m HMDP bone imaging and Tl-201 tumor imaging strongly suggested that the cause of this rare syndrome was a small metastatic tumor. Although the therapeutic effect was also difficult to assess by anatomic imaging alone, dual-isotope SPECT after radiation therapy showed a decline of tumor viability.

Aged↗
PubMed1998

Diagnosis of lung cancer using two-phase Tl-201 SPECT and modified retention image to view tumor in the collapsed lung: comparison with bolus CT.

In this report the usefulness of Tl-201 SPECT and modified retention images in the differentiation of lung cancer and postobstructive collapse was studied. Two-phase Tl-201 SPECT was performed in 20 lung cancer lesions in which postobstructive collapse was suspected on CT. Retention imaging was done afterward. Three types of Tl-201 images were compared with the bolus CT images. Bolus CT differentiated lung cancer from postobstructive collapse in 7 of the 20 lesions (35%). Tl-201 SPECT differentiated the two conditions in 9 of 20 lesions (45%) on early Tl-201 SPECT and in 13 of 20 lesions (65%) on delayed imaging. With modified retention images, differentiation was possible in 13 of 20 lesions (65%). By combining delayed Tl-201 SPECT and modified retention images, lung cancer alone could be demonstrated in 18 of 20 lesions (90%). Combined delayed Tl-201 SPECT and modified retention images were more effective than bolus CT in delineating the extent of lung cancer in the presence of postobstructive collapse.

Aged↗
PubMed1998

Relationship between ATP synthesis and 201Tl uptake in transformed and non-transformed cell lines.

201Tl tumour imaging is an established procedure, but little is known about its biological significance in transformed and non-transformed cells. In investigating the relationship between 201Tl uptake and intracellular ATP, we wished to determine whether the observed difference in delayed uptake is attributable to re-uptake via Na-K ATPase by using transformed (HeLa) and non-transformed (human fibroblast: hFB) cell lines. In each cell line, ATP was measured using the Luciferin-Luciferase method (LLM). The change in 201Tl uptake was assessed under conditions of mitochondrial suppression. Additionally, we assessed whether glycolysis is involved in 201Tl uptake under conditions of mitochondrial suppression and anaerobic incubation. Re-uptake via Na-K ATPase (HeLa vs hFB: 37.3 vs 24.2%) showed a clear difference in delayed uptake between HeLa and hFB. With HeLa, 201Tl uptake decreased biphasically with a reduction in ATP levels, whereas with hFB a linear correlation was evident. Despite the suppression of mitochondrial potential, a 5% glucose loading accelerated glycolysis with HeLa, and increased ATP (10.0 +/- 4.0%) and 201Tl uptake (16.2 +/- 3.0%). Conversely, neither ATP nor 201Tl uptake increased with hFB. Our results provide evidence that 201Tl uptake in transformed cells is related to enhanced glycolysis as well as mitochondrial ATP synthesis.

2,4-Dinitrophenol↗
PubMed1998

Alteration of hormone levels in transgenic tobacco plants overexpressing the rice homeobox gene OSH1.

The rice (Oryza sativa L.) homeobox gene OSH1 causes morphological alterations when ectopically expressed in transgenic rice, Arabidopsis thaliana, and tobacco (Nicotiana tabacum L.) and is therefore believed to function as a morphological regulator gene. To determine the relationship between OSH1 expression and morphological alterations, we analyzed the changes in hormone levels in transgenic tobacco plants exhibiting abnormal morphology. Levels of the plant hormones indole-3-acetic acid, abscisic acid, gibberellin (GA), and cytokinin (zeatin and trans-zeatin [Z]) were measured in leaves of OSH1-transformed and wild-type tobacco. Altered plant morphology was found to correlate with changes in hormone levels. The more severe the alteration in phenotype of transgenic tobacco, the greater were the changes in endogenous hormone levels. Overall, GA1 and GA4 levels decreased and abscisic acid levels increased compared with wild-type plants. Moreover, in the transformants, Z (active form of cytokinin) levels were higher and the ratio of Z to Z riboside (inactive form) also increased. When GA3 was supplied to the shoot apex of transformants, internode extension was restored and normal leaf morphology was also partially restored. However, such GA3-treated plants still exhibited some morphological abnormalities compared with wild-type plants. Based on these data, we propose the hypothesis that OSH1 affects plant hormone metabolism either directly or indirectly and thereby causes changes in plant development.

Homeodomain Proteins↗
PubMed1998

Decreased GA1 content caused by the overexpression of OSH1 is accompanied by suppression of GA 20-oxidase gene expression.

We previously reported that overexpression of the rice homeobox gene OSH1 led to altered morphology and hormone levels in transgenic tobacco (Nicotiana tabacum L.) plants. Among the hormones whose levels were changed, GA1 was dramatically reduced. Here we report the results of our analysis on the regulatory mechanism(s) of OSH1 on GA metabolism. GA53 and GA20, precursors of GA1, were applied separately to transgenic tobacco plants exhibiting severely changed morphology due to overexpression of OSH1. Only treatment with the end product of GA 20-oxidase, GA20, resulted in a striking promotion of stem elongation in transgenic tobacco plants. The internal GA1 and GA20 contents in OSH1-transformed tobacco were dramatically reduced compared with those of wild-type plants, whereas the level of GA19, a mid-product of GA 20-oxidase, was 25% of the wild-type level. We have isolated a cDNA encoding a putative tobacco GA 20-oxidase, which is mainly expressed in vegetative stem tissue. RNA-blot analysis revealed that GA 20-oxidase gene expression was suppressed in stem tissue of OSH1-transformed tobacco plants. Based on these results, we conclude that overexpression of OSH1 causes a reduction of the level of GA1 by suppressing GA 20-oxidase expression.

Amino Acid Sequence↗
PubMed1998

[Early manifestation of septic shock and disseminated intravascular coagulation complicated by acute myocardial infarction in a patient suspected of having Legionnaires' disease].

Legionellosis is an important cause of severe pneumonia in the community. Inadequate therapy will lead to respiratory distress syndrome, disseminated intravascular coagulation (DIC) and finally fatal multiple organ failure. We encountered a rare case in which early manifestation included septic shock and DIC complicated by acute myocardial infarction (AMI) suspected to be derived from Legionnaires' disease. A 54-year-old healthy female complained of lumbago, high fever and dry cough 10 days after visiting a hot spring spa. She was emmergently admitted due to shock. Physical examination demonstrated hypotension, high fever, course creakle in the right lower lung. Hepatosplenomegaly, lymphadenopathy and eruption were not found. WBC count was 34600/microliters with nuclear shift. CRP elevated. FDP, D dimer and TAT also elevated CPK elevated with dominance of the MB isozyme. Chest roentogenography revealed congestive heart failure, pleural effusion and obscure pneumonic shadow and EKG showed ST segment elevation in leads I, II, III, aVF, V4, V5, and V6. The patient was diagnosed as having septic shock, DIC and AMI. She was treated with gabexate mesilate, high dose methyl prednisolone and dopamine hydrochloride as well as piperacillin, meropenem, isepamycin and fluconzaole. Despite intensive care, the blood pressure fell again and pneumonia had progressed on the 8th hospital day. These antibiotics appeared to be ineffective. Erythromycin was then administered and a dramatic effect. was obtained as the patient recovered. Serum titer of Legionella pneumophila (serogroup 1) rose to 128-fold 2 weeks after the onset. Other serum titers such as Chlamydia psittaci, Rickettsia, Mycoplasma were all negative. Cultures obtained from the sputum, throat swab, urine and blood did not yield any microorganisms. Although the diagnosis could not be confirmed because the titer did not elevate over 256-fold of 4-fold within 2 weeks after the onset, Legionella infection was highly suspected from the clinical features. This is a rare case in which septic shock and DIC with AMI preceded pulmonary symptoms in a non-immunocompromised patient.

Diagnosis, Differential↗
PubMed1998

Rapid and progressive CD4+ decline in a monkey infected with an SIV+HIV-1 chimeric virus.

We previously constructed a simian immunodeficiency virus+human immunodeficiency virus type 1 (HIV-1) chimeric virus, NM-3rN to generate a pathogenic HIV-1 in macaque monkeys. During the in vivo passage of this virus in several monkeys, a viral strain, R43-56 was obtained which acquired a better replication ability in vivo. MM121, one of the three monkeys inoculated with the R43-56, showed weight loss, diarrhea and a rapid and continuous decrease in CD4+ lymphocytes at the moribund stage. An autopsy revealed generalized lymphadenopathy, dehydration, and ileocecal intussusception. In situ hybridization showed that the virus infection was in systemic lymphoid organs. We are presently monitoring the survivors to obtain candidates for a more virulent virus. R43-56 may be a better challenge virus and useful tool for human acquired immunodeficiency syndrome research.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Feces, flies, and fetor: findings from a Peruvian shantytown.

Sanitary disposal of feces is vital to combat childhood diarrhea, and its promotion is key to improving health in developing countries. Knowledge of prevailing feces disposal practices is a prerequisite to formulation of effective intervention strategies. Two studies were conducted in a shantytown area of Lima, Peru. First, information was gathered through in-depth interviews with mothers and structured observations (4 hours) of young children and their caretakers. Data on beliefs and practices related to feces disposal behaviors were obtained. Excreta were deposited by animals or humans in or near the house in 82% of households observed. Beliefs about feces depended on their source and were reflected in how likely the feces were to be cleared. While 22% of children aged > or = 18 months were observed to use a potty for defecation, 48% defecated on the ground where the stools often remained. Although almost all children were cleaned after defecation, 30% retained some fecal matter on their body or clothes. Handwashing after the child's defecation was extremely rare for both children (5%) and caretakers (20%). The hygienic disposal of feces poses problems in this type of community. Nevertheless existing practices were found that show promise for promotion on a wider scale, including greater use of potties.

Feces↗