Search PubMed⌕ Search

Biomedical subjects

K Fukuda

Publications and source records attributed to K Fukuda.

At least 253 records · Page 14Linked to original sources

Prevalence of hypoxemia in 102 Japanese patients with alcoholic and nonalcoholic cirrhosis.

OBJECTIVE: Liver cirrhosis is often accompanied by arterial hypoxemia in the absence of cardiopulmonary disease. The aim of this study was to investigate the relationship between various clinicopathological conditions and the hypoxemia seen in Japanese patients with liver cirrhosis. METHODS: In 102 consecutive patients with alcoholic (N = 45) and nonalcoholic (N = 57) cirrhosis not associated with cardiopulmonary disease, we performed lung perfusion scintigraphy, contrast echocardiography, and arterial blood gas analysis and measured oxygen consumption. RESULTS: No abnormality was seen in pulmonary blood flow in cirrhotic patients, but 38 (38%) of them had a decreased partial pressure of oxygen (PaO2). The hypoxemic patients did not show any pulmonary signs or symptoms. The hypoxemia was not associated with the Child-Pugh grade, and was observed in 32 (71%) of the 45 alcoholic patients but in only six (11%) of the 57 nonalcoholic patients (p < 0.001). Oxygen consumption was significantly higher in the alcoholic group than in the nonalcoholic group (p < 0.0001), and a high incidence of oxygen consumption was seen in all 45 (100%) of the alcoholic patients and in 34 (60%) of the nonalcoholic subjects, the difference being significant (p < 0.01). The relationship between oxygen consumption and PaO2 in the 102 cirrhotic patients showed an inverse correlation (r = -0.85, p < 0.0001). Among the alcoholic patients, the incidence of hypoxemia did not differ between the 33 smokers and the 12 nonsmokers. After 1 wk of abstinence from alcohol a significant increase (p < 0.0001) in the PaO2 was seen in 14 of 19 patients with alcoholic cirrhosis. CONCLUSIONS: We conclude that the hypoxemia in Japanese patients with liver cirrhosis occurs mainly in drinking alcoholic patients, presumably due to an increased oxygen consumption by alcohol.

Aged↗

Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays.

From May to December 1997, 18 cases of mild to severe respiratory illness caused by avian influenza A (H5N1) viruses were identified in Hong Kong. The emergence of an avian virus in the human population prompted an epidemiological investigation to determine the extent of human-to-human transmission of the virus and risk factors associated with infection. The hemagglutination inhibition (HI) assay, the standard method for serologic detection of influenza virus infection in humans, has been shown to be less sensitive for the detection of antibodies induced by avian influenza viruses. Therefore, we developed a more sensitive microneutralization assay to detect antibodies to avian influenza in humans. Direct comparison of an HI assay and the microneutralization assay demonstrated that the latter was substantially more sensitive in detecting human antibodies to H5N1 virus in infected individuals. An H5-specific indirect enzyme-linked immunosorbent assay (ELISA) was also established to test children's sera. The sensitivity and specificity of the microneutralization assay were compared with those of an H5-specific indirect ELISA. When combined with a confirmatory H5-specific Western blot test, the specificities of both assays were improved. Maximum sensitivity (80%) and specificity (96%) for the detection of anti-H5 antibody in adults aged 18 to 59 years were achieved by using the microneutralization assay combined with Western blotting. Maximum sensitivity (100%) and specificity (100%) in detecting anti-H5 antibody in sera obtained from children less than 15 years of age were achieved by using ELISA combined with Western blotting. This new test algorithm is being used for the seroepidemiologic investigations of the avian H5N1 influenza outbreak.

Adolescent↗

Decreased plasma tryptophan associated with deep white matter lesions in elderly subjects.

The aim was to identify potentially treatable risk factors for cerebral white matter lesions often found on MRI in elderly persons. findings were assessed on 1.0 T MRI of 178 subjects living in the community and aged 60 years or older. Participants underwent standardised evaluations including standard questionnaires, a physical and neurological examination, cognitive function tests, electrocardiogram, a complete blood chemistry panel, and plasma amino acid measurements. Brain MRI infarcts, deep white matter lesions (DWMLs), and periventricular hyperintensities were found in 26%, 43%, and 29% of the 178 participants, respectively. Subjects with DWMLs were significantly older and had a higher frequency of hypertension, higher systolic blood pressure, and more brain infarcts, but lower plasma concentrations of tryptophan. In the multivariate model, greater age and lower plasma tryptophan concentrations were independently associated with DWMLs. Tryptophan concentrations were inversely related to DWML grading, whereas hypertension and brain infarction were more common in subjects with higher extents of DWMLs. The present study suggests that greater age and lower plasma tryptophan concentrations were important in producing DWMLs in elderly subjects.

Aged↗

Effects of ginseng radix on sugar absorption in the small intestine.

Ginseng radix (GR) is often used in traditional Japanese kampo medicine. We studied the effect of GR on glucose and maltose transport in rat and human duodenal mucosa by Ussing's method, and on smooth muscle movement in rat duodenal muscle by Magnus' method. GR inhibited absorption of glucose or maltose in rat and human duodenal mucosa, but increased duodenal muscle movement. It suggests that the inhibition of sugar absorption by GR is more dominant than enhancement of duodenal muscle movement by GR.

Adult↗

Apoptosis and overexpression of bax protein and bax mRNA in smooth muscle cells within intimal hyperplasia of human radial arteries : analysis with arteriovenous fistulas used for hemodialysis.

There is a type of arteriosclerosis with remodeling of middle-size arteries in which intimal hyperplasia of smooth muscle cells (SMCs) plays the main role, and there are few macrophages, T lymphocytes, and foam cells. It is unknown whether apoptosis and the expression of Bax, an inducer of apoptosis, are increased according to the progression of this type of human arteriosclerosis, which is different from so-called atherosclerosis. Bax heterodimerizes with Bcl-2, an inhibitor of apoptosis, and the ratio of Bax to Bcl-2 determines cellular apoptosis or survival. Thus, we investigated apoptosis and the expressions of Bax, bax mRNA, and Bcl-2 in human arteriovenous (AV) fistulas used for hemodialysis, a representative of arteriosclerosis of the aforementioned type. The material was 20 radial arteries obtained from 20 patients with chronic renal failure undergoing AV shunt surgery. SMCs, macrophages, and T lymphocytes were immunohistochemically identified at the light microscopic (LM) level. Apoptosis was detected by in situ terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-dUTP nick end labeling (TUNEL) at both the LM and electron microscopic (EM) level. Cell proliferating activity was estimated by proliferating cell nuclear antigen (PCNA). Bax and Bcl-2 were detected by immunohistochemistry and Western blot analysis. Expression of bax mRNA was detected by in situ hybridization. LM TUNEL-positive cells in both the intima and media were significantly increased according to the percent stenosis of the vessels. EM analysis revealed that ultrastructures of apoptotic SMCs were seen in both synthetic and contractile phenotypes. Their frequency of occurrence in the intima and media were greater in those vessels with >50% stenosis than in those with <50% stenosis (5.2+/-0.7% versus 1.0+/-0.3% in the intima and 2. 1+/-0.5% versus 0.2+/-0.1% in the media). The proportion of apoptotic SMCs with ruptured plasma membranes was greater than that of apoptotic SMCs with intact membranes in the intima of the former (4.1+/-0.6% versus 1.1+/-0.1%). Only those SMCs with apoptotic ultrastructures had TUNEL-positive nuclei with moderate or marked accumulation of immunogold particles at the EM level. However, ultrastructures of oncosis (primary necrosis) were not observed. Immunohistochemical analyses showed significant positive correlations between percent stenosis of vessels and the percentage of either PCNA-positive intimal cells or Bax-positive areas in the intima and media. Bcl-2-positive cells were not observed in the intima but mainly in the outer media. The percentage of Bcl-2-positive medial cells was definitely decreased at an early stage after formation of the AV fistula but did not change according to the duration of hemodialysis or the progression of arteriosclerosis. Western blot analysis of Bax or Bcl-2 and in situ hybridization of bax mRNA confirmed the immunohistochemical data. Thus, regulation of cellularity in intimal hyperplasia of SMCs in human arteriosclerosis with remodeling is mediated by proliferation and apoptosis but not oncosis. The apoptosis is probably induced by an increase in the Bax to Bcl-2 ratio.

Adult↗

Cardiomyocytes can be generated from marrow stromal cells in vitro.

We have isolated a cardiomyogenic cell line (CMG) from murine bone marrow stromal cells. Stromal cells were immortalized, treated with 5-azacytidine, and spontaneously beating cells were repeatedly screened. The cells showed a fibroblast-like morphology, but the morphology changed after 5-azacytidine treatment in approximately 30% of the cells; they connected with adjoining cells after one week, formed myotube-like structures, began spontaneously beating after two weeks, and beat synchronously after three weeks. They expressed atrial natriuretic peptide and brain natriuretic peptide and were stained with anti-myosin, anti-desmin, and anti-actinin antibodies. Electron microscopy revealed a cardiomyocyte-like ultrastructure, including typical sarcomeres, a centrally positioned nucleus, and atrial granules. These cells had several types of action potentials, such as sinus node-like and ventricular cell-like action potentials. All cells had a long action potential duration or plateau, a relatively shallow resting membrane potential, and a pacemaker-like late diastolic slow depolarization. Analysis of the isoform of contractile protein genes, such as myosin heavy chain, myosin light chain, and alpha-actin, indicated that their muscle phenotype was similar to that of fetal ventricular cardiomyocytes. These cells expressed Nkx2.5/Csx, GATA4, TEF-1, and MEF-2C mRNA before 5-azacytidine treatment and expressed MEF-2A and MEF-2D after treatment. This new cell line provides a powerful model for the study of cardiomyocyte differentiation.

Action Potentials↗

Postmortem evaluation of morphologic changes in the infarcted myocardium that predict ventricular septal rupture in acute anteroseptal infarction.

Although thinning of the ventricular wall due to infarct expansion (septal aneurysm) may contribute to ventricular septal rupture (VSR), spatial factors predisposing to this mechanical complication have not been fully demonstrated. To identify the morphologic predictors of VSR, a retrospective postmortem study was performed on 17 hearts with acute anteroseptal myocardial infarction, comprising 7 with VSR and 10 without rupture. Infarct size and the extent of wall thinning were quantified. Wall thinning was defined as a decrease of less than 50% of thickness of the noninfarcted wall. The total infarct size did not differ among the groups. In the free wall (FW), the infarct was smaller in hearts with VSR than in those with a ruptured FW (p<0.05) or no rupture (p<0.01). The septal involvement was more extensive in patients with VSR than in those with FW rupture (p<0.05). Septal thinning was more extensive in hearts with VSR than in those with FW rupture (p<0.05) or non-rupture (p<0.05). A combination of a small infarct of the FW and a large septal infarct may contribute to the formation of septal aneurysm, which is believed to predispose to VSR. The presence of a small infarct of the anterior septum may be another setting for postinfarction septal rupture.

Aged↗

Hexavalent chromium responsible for lung lesions induced by intratracheal instillation of chromium fumes in rats.

Lung toxicity of chromium fumes (Cr fumes) was examined by a single intratracheal instillation into rats of 10.6 mg and 21.3 mg Cr fumes/kg body weight and by repeated (3 times) instillations of 10.8 mg and 21.7 mg Cr fumes/kg. The pathological changes were compared with those induced by single administrations of 3.2 mg and 19.2 mg Na2CO3 solution-insoluble fraction of Cr fumes (Cr-Fr)/kg and 20.8 mg commercially available chromium (III) oxide powder (Cr (III) oxide)/kg. Single and repeated administrations of Cr fumes suppressed growth rate in a dose-dependent manner, but administrations of Cr-Fr and Cr (III) oxide did not. A single administration of Cr fumes produced granulomas in the entire airways and alveoli with progressive fibrotic changes, as well as severe mobilization and destruction of macrophages and foamy cells. Those histopathological changes were aggravated by the repeated administration of Cr fumes. On the other hand, single administrations of Cr-Fr and Cr (III) oxide produced no remarkable histopathological changes. Cr fumes were found to be composed of 73.5% chromium (III) oxide and 26.5% chromium (VI) oxide. The primary particles of Cr fumes and Cr-Fr were similar, 0.02 micron in size (sigma g: 1.25), and Cr (III) oxide particles were 0.30 micron in size (sigma g: 1.53), measured by analytical electron microscopy (ATEM). Diffuse clusters of the primary particles in Cr fumes were identified as Cr (VI) oxide. The present results suggested that the lung toxicity of Cr fumes was mainly caused by these Cr (VI) oxide (CrO3) particles in Cr fumes.

Administration, Inhalation↗

[A case of noninflammatory corneal edema following anterior-posterior radial keratotomy successfully treated by topical steroids].

BACKGROUND: Corticosteroids seems to affect the functions of corneal endothelial cells directly in addition to its anti-inflammatory effect. CASE: A 69-year-old male presented with left blurred vision and decreased visual acuity in both eyes. He had undergone anterior-posterior radial keratotomy for myopia in both eyes 40 years before. Both eyes showed mild corneal stromal edema in the pupil area. We diagnosed the condition as corneal edema secondary to cell loss and dysfunction of corneal endothelium after surgery. The stromal edema further advanced in the left eye one month later. The corneal thickness increased from the initial value of 619 to 631 microns. The corrected visual acuity decreased from 0.5 to 0.06. There were no signs suggesting inflammatory reaction. The left eye was then treated with topical corticosteroids as eye-drops and by subconjunctival injection. The corneal thickness decreased to 546 microns two months later with improvement of visual acuity to 0.5. CONCLUSION: This case illustrates that topical corticosteroids may be effective for corneal edema through their anti-inflammatory effect and possible activation of the endothelium.

Administration, Topical↗

[A case of pleural and mediastinal lymph node metastases from breast cancer effectively treated with fadrozole hydrochloride in combination with cyclophosphamide].

A 63-year-old woman was diagnosed with pleural and mediastinal lymph node metastases 116 months after operation because of bilateral breast cancer. She was then treated with fadrozole hydrochloride (FH) (2 mg). Adriamycin (30 mg) administration into the pleural cavity was attempted, but did not prove effective. Thus, we tried to combine FH with cyclophosphamide (100 mg). After one month, chemoendocrine therapy relieved her complaints of cough and shortness of breath. CT revealed a remarkable decrease of pleural effusion and disappearance of mediastinal lymph nodes. She was alive 9 months after the treatment. Fadrozole hydrochloride in combination with cyclophosphamide is promising as an effective treatment in postmenopausal patients.

Antineoplastic Combined Chemotherapy Protocols↗

Angiogenic interaction between retinal endothelial cells and pericytes from normal and diabetic rabbits, and phenotypic changes of diabetic cells.

Retinal endothelial cells (ECs) and pericytes (PCs) were cloned and cultured from normal and diabetic rabbits to clarify the mechanism of diabetic proliferative retinopathy from the viewpoint of the interaction between ECs and PCs, and phenotypic changes of diabetic cells. PC-conditioned medium (PC-CM) from normal rabbits stimulated in vitro angiogenesis of diabetic ECs more than that of normal ECs. in vitro angiogenesis was also more stimulated in diabetic ECs than in normal ECs by basic fibroblast growth factor (bFGF) or transforming growth factor-beta 1, indicating that diabetic ECs are different from normal ECs in terms of angiogenic potential. One mechanism of this property of diabetic ECs was the acceleration of cell proliferation but not of cell migration, because diabetic ECs grew more rapidly but did not migrate more than normal ECs in response to PC-CM or bFGF. Moreover, PC-CM from diabetic PCs stimulated angiogenesis of normal ECs more than that from normal PCs, indicating that diabetic PCs secreted more angiogenic factor(s) than normal PCs. The angiogenic, mitogenic and migratory activities of PC-CM both from normal and diabetic PCs were similarly inhibited by an anti-bFGF antibody. Western blot analysis revealed this factor to be a bFGF-like molecule. These data indicate that the interaction between ECs and PCs and the phenotypic changes of diabetic ECs and PCs both contribute to the proliferative retinopathy in diabetes.

Animals↗

[Periosteal reaction].

The periosteal membrane covers the cortical bone except for the articular surface. The deep layer of the periosteum contains bone-forming mesenchymal cells, capillaries, and nerves. This layer is more active in infants than in adults. Prostaglandin osteopathy, infantile cortical hyperostosis, hypervitaminosis A, and congenital syphilis are examples of periostitis in infants. Incidental asymptomatic periosteal reactions are usually either physiological changes or cortical bone irregularities simulating periostitis. On the other hand, symptomatic periosteal reactions of single bone, such as bone tumor, tumor-like lesion, infection, and trauma, are always pathologic. Careful radiological analysis of periosteal reactions is needed to evaluate the activity and aggressiveness of the lesions. Periosteal reactions of multiple bones usually show solid smooth or undulating patterns. They include pachydermoperiostosis, secondary hypertrophic osteoarthropathy, vascular insufficiency, renal osteodystrophy, and thyroid acropachy. These are usually skeletal manifestations of systemic disorders.

Adult↗

Troglitazone inhibits bicarbonate secretion in rat and human duodenum.

Troglitazone is a new, orally effective antidiabetic agent that decreases plasma glucose in obese patients with non-insulin-dependent diabetes mellitus. Unfortunately, troglitazone also has a propensity to cause edema. This study was designed to determine how troglitazone affects intestinal ion transport and water absorption. Short circuit current (I(sc)) was measured in rat and human duodenal mucosa in Ussing chambers. Five minutes later, the serosal addition of troglitazone caused I(sc) to decrease gradually, and after 50 min, I(sc) reached the peak of decrease. EC(50) values and maximum response to I(sc) in rat and human mucosa were 8.4 and 8.7 microM and 8.56 +/- 1.0 and 8.00 +/- 2.0 microA/cm(2), respectively. In an HCO(3)(-)/CO(2)-free system, the decrease in I(sc) caused by troglitazone was 1.31 +/- 0.83 microA/cm(2). When 10 mM acetazolamide was preadministered, the small decrease in I(sc) evoked by troglitazone (20 microM) was 4.56 +/- 0.22 microA/cm(2), whereas the preadministration of 100 microM amiloride and 100 nM tetrodotoxin did not influence the decrease in I(sc) evoked by troglitazone. The serosal preadministration of 100 nM vasoactive intestinal peptide potently enhanced the decrease in I(sc) evoked by 20 microM troglitazone (21.1 +/- 1.63 microA/cm(2)). The cyclic AMP contents of rat duodenal mucosa incubated with and without troglitazone (20 microM) for 50 min were 3.2 +/- 0.25 and 5. 8 +/- 0.46 pmol/mg protein, respectively (P <.01). These results indicate that the ionic basis for the decrease in I(sc) that is induced by troglitazone may be inhibition of electrogenic bicarbonate secretion. The alteration of intestinal ion transport by troglitazone could cause edema.

Animals↗

[A case of adriamycin and methotrexate-resistant recurrent breast cancer treated with doxifluridine and mitomycin C].

A 49-year-old woman was diagnosed with local recurrence and cervical lymph node and bone metastases 55 months after surgery for breast cancer. She was treated with goserelin acetate and tamoxifen but the disease was assessed as progressive after 8 months. Five courses of CMF therapy were performed but lung, pleural and mediastinal lymph node metastases were detected. Then, five courses of CAF therapy were carried out, but a contralateral breast metastasis was detected and the patient complained of shortness of breath. The CAF therapy was assessed as PD. We attempted administration of doxifluridine (5'-DFUR) and mitomycin C (MMC) on an outpatient basis. After 6 months, no progressive disease was detected and she was relieved of her shortness of breath. The combination therapy was assessed as long NC. Combination therapy with 5'-DFUR and MMC is thus a useful treatment for adriamycin- and methotrexate-resistant breast cancer, especially in terms of quality of life.

Antimetabolites, Antineoplastic↗

[Intraarterial infusion therapy for unresectable liver metastasis of colorectal cancer].

Forty-two colorectal carcinomas with metastatic liver tumor at four hospitals were investigated retrospectively. The number of patients in H factor 1, 2 and 3 were 8, 12 and 21, respectively. The diameter of the maximum liver tumor ranged from 10 to 160 mm (average 45 mm). The number of liver tumors were from 1 to 50 (average 7.3). The 6-, 12-, 18-, 24- and 32-month cumulative survival rates were 88, 67, 36, 24%, and 7%, respectively. The response rate reached 45%, and the survival period of the responder was significantly more prolonged than that of the unresponder (p = 0.04). No significant survival periods were recognized in terms of the method of injection, injected drug and the amounts of 5-FU. But the response rate of FP injection was best. Patients serum CEA levels at 1 or 3 months were decreased, and the survival periods were significantly longer than for increased patients. No significant difference was found among the side effects, the amounts of 5-FU, and the method of injection. The patients injected with MMC frequently suffered from G 2 or G 3 side effects.

Adult↗

Long-term treatment of portosystemic encephalopathy with oral branched-chain amino acids--a case report.

We treated a 68-year-old male patient of hepatic encephalopathy with oral branched chain amino acids-enriched formula (Aminoleban EN) in addition to lactulose. His encephalopathy was successfully controlled with this therapy for more than a year despite the high blood ammonia levels. Repeated amino acids analyses demonstrated that the deranged branched chain to aromatic amino acids ratio was attenuated with long-term Aminoleban EN administration both in plasma and in cerebrospinal fluid. Oral branched-chain amino acid supplement was very useful in improving the chronic portosystemic or hepatic encephalopathy in this patient.

Administration, Oral↗

[Power Doppler US in breast masses: correlation of spectral analysis findings with pathological features].

The purpose of this study was to clarify the usefulness of power Doppler imaging for the diagnosis of breast masses. Materials were histologically confirmed breast masses: 24 benign lesions, 4 non-invasive carcinomas, and 54 invasive carcinomas. In invasive breast carcinoma, pathological examination was used to classify the degree of intratumor fibrous stroma (IFS) into three groups. The relationships between IFS and Doppler spectral parameters (Vmax, Vmin, PI, RI) were evaluated retrospectively. High PI and low Vmin values were well correlated with IFS grade. Carcinomas with low IFS grades had higher Vmax values than benign lesions.

Adult↗