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Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 217 records · Page 12Linked to original sources

Differentiation of small solitary pulmonary nodules using Tc-99m MIBI and Tl-201 SPECT

The authors evaluated the ability of dual SPECT with Tc-99m MIBI and Tl-201 chloride to differentiate malignant and benign solitary pulmonary nodules smaller than 3 cm in diameter. Forty-three patients had solitary pulmonary nodules smaller than 3 cm in diameter based on the findings of chest CT. All patients underwent dual-isotope SPECT with Tc-99m MIBI and Tl-201 chloride. Regions of interest were placed over the tumors (T) and contralateral normal lung tissue (N) on one coronal SPECT view, and T:N ratios and retention indices were calculated. The sensitivities of early and delayed Tc-99m MIBI SPECT and early and delayed Tl-201 chloride SPECT for differentiating malignant and benign lesions were 44%, 48%, 56%, and 52%, respectively. The corresponding specificity rates were 44%, 56%, 25%, and 31%, respectively, and corresponding accuracy rates were 44%, 51%, 44%, and 44%, respectively. There were no statistically significant differences between malignant and benign lesions in the early and delayed T:N ratios for Tc-99m MIBI and Tl-201 chloride and the retention index for Tc-99m MIBI. However, the retention index using Tl-201 chloride in malignant lesions was significantly higher (P < 0.01) than that in benign lesions. Analysis of semiquantitative parameters of the T:N ratio and retention index from Tc-99m MIBI SPECT appears to have little or no value for differentiating malignant from benign solitary pulmonary nodules smaller than 3 cm in diameter. However, the retention index using Tl-201 chloride seems to be a better parameter for differentiating between these malignant and benign lesions.

Journal Article↗

Hypercalcaemia in melanoma patients associated with increased levels of parathyroid hormone-related protein.

We analysed serum levels of calcium and parathyroid hormone-related protein (PTH-rP) in 59 patients with melanoma by immunoradiometric assay, since only a few studies have been conducted on hypercalcaemia and serum levels of PTH-rP in patients with melanoma. Hypercalcaemia was found in seven of the 59 patients with melanoma. The serum level of PTH-rP was increased in three of the 59 patients and two of the three showed hypercalcaemia. All the patients with hypercalcaemia and/or an increased level of PTH-rP had stage IV melanoma. These findings suggest that hypercalcaemia is much more common than previously reported in patients with advanced stage melanoma and that an increased serum level of PTH-rP is one of the causative factors in hypercalcaemia in melanoma. Analysis of the serum PTH-rP level will contribute to the monitoring of the clinical course of patients with advanced stage melanoma.

Adolescent↗

Interferon treatment of two patients with quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV).

We administered interferon (IFN) to two patients who had quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV), a recently isolated novel DNA virus. Nine mega-units of natural alpha-IFN were administered daily during the first two weeks and thrice weekly during the following 22 weeks (total dose, 720 mega-units). In both cases, serum alanine aminotransferase (ALT) levels decreased during IFN administration but increased thereafter. The concentrations of HCV, HIV, HGV, and TTV declined with the administration of IFN. However, the concentrations of these 4 viruses increased after the cessation of IFN with the except of TTV in patient 2 which disappeared during treatment and did not subsequently reappear. IFN reduced the concentrations of 4 viruses, in an apparently independent manner.

Adult↗

Presence of multiple genotype-specific antibodies in patients with persistent infection with hepatitis C virus (HCV) of a single genotype: evidence for transient or occult superinfection with HCV of different genotypes.

OBJECTIVE: We investigated the significance of multiple genotype-specific antibodies in patients with persistent infection with hepatitis C virus (HCV) of a single genotype. METHODS: Titers of genotype-specific antibodies to group 1 and 2 HCV polypeptides in the NS4 region of HCV were measured in 53 hemophiliacs and 58 nonhemophiliacs who were persistently infected with HCV of a single genotype. In addition, sequence variability in hypervariable region 1 (HVR1) of HCV was evaluated in these patients. RESULTS: The presence of antibodies to both group 1 and 2 polypeptides, reflecting a mixture of serotypes, was more frequent in hemophiliacs (11 of 53 patients, 20.8%) than in nonhemophiliacs (two of 58 patients, 3.4%; p = 0.01). HVR1 sequence variability in 13 patients with mixed serotypes was higher than in 87 patients with a single serotype (21.1 +/- 4.3% vs 8.5 +/- 6.3%; p < 0.01). CONCLUSIONS: A mixture of HCV serotypes was more common in hemophiliacs with persistent HCV infection of a single genotype who were at high risk of exposure to HCV than in nonhemophiliacs, and the sequence variability of the infecting strains was high in these patients. These data are suggestive of the effects of superinfection with HCV of different genotypes. The presence of multiple genotype-specific antibodies to HCV may be evidence of transient or occult superinfection with HCV of different genotypes in patients with persistent infection by HCV of a single genotype.

Adolescent↗

High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis.

BACKGROUND: High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 have been identified as novel antigens of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCAs), and the existence of anti-HMG1 and anti-HMG2 antibodies in a population of patients with ulcerative colitis has been reported. AIMS: To investigate whether HMG1 and HMG2 are target antigens for p-ANCAs in autoimmune hepatitis (AIH). PATIENTS: Serum samples from 28 patients with AIH, 44 patients with primary biliary cirrhosis (PBC), 27 patients with chronic hepatitis C, and 23 patients with chronic hepatitis B were tested. METHODS: ANCAs were detected by routine indirect immunofluorescence (IIF). Anti-HMG1 and anti-HMG2 antibodies were assayed by enzyme linked immunosorbent assay. RESULTS: p-ANCAs were detected in 89% (25/28) of patients with AIH, 36% (16/44) of patients with PBC, 11% (3/27) of patients with chronic hepatitis C, and 13% (3/23) of patients with chronic hepatitis B. Anti-HMG1 and/or anti-HMG2 antibodies were detected in 89% (25/28) of patients with AIH, 70% (31/44) with PBC, 26% (7/27) with chronic hepatitis C, and 9% (2/23) with chronic hepatitis B. In AIH, anti-HMG1 and/or anti-HMG2 antibodies were detected in 96% (24/25) of p-ANCA positive patients. The p-ANCA staining pattern detected by IIF using sera from patients with AIH disappeared or decreased in titre after preincubation with a mixture of HMG1/HMG2. The presence and titres of those antibodies in AIH correlated significantly with those of p-ANCA, but not with those of anti-nuclear antibody or anti-smooth muscle antibody. CONCLUSIONS: HMG1 and HMG2 are significant target antigens of p-ANCA in AIH.

Adult↗

Localization of matrix metalloproteinases and tissue inhibitor of metalloproteinases-2 in normal human and rabbit stomachs.

BACKGROUND/AIMS: Matrix metalloproteinases (MMPs) are endopeptidases that degrade extracellular matrix and are involved in the pathogenesis of gastrointestinal ulcer and cancer along with tissue inhibitors of metalloproteinases (TIMPs). The purpose of this study is to examine their localization and functions in the normal stomach. METHODS: We examined the localization of MMP-1, MMP-2, MMP-9 and TIMP-2 in normal human and rabbit stomachs by light- and electron-microscopic immunohistochemistry and Western blotting, and the enzymatic activities of MMP-2 and MMP-9 by gelatin zymography. RESULTS: Immunohistochemistry revealed their localization in parietal cells, and surface and foveolar epithelial cells. Electron-microscopic immunohistochemistry of parietal cells showed immunolabeling of MMP-2 and TIMP-2 in the cisternae of the rough endoplasmic reticulum, and that of MMP-1 and MMP-9 in tubular structures in their cytoplasm. Western blotting revealed that the densities of MMP-2 and MMP-9 bands were higher for the fundic gland region than for the pyloric gland region. Gelatin zymography revealed that tissue extracts of the fundic gland region exhibited higher enzymatic activity of MMP-2 and MMP-9 than those of the pyloric gland region. CONCLUSION: Normal rabbit and human stomachs contain MMP-1, MMP-2, MMP-9, and TIMP-2 and these are mainly localized in, and synthesized by parietal cells.

Adult↗

Acyclovir treatment of skin lesions results in immune deviation in mice infected cutaneously with herpes simplex virus.

Clinical observations indicate that the antibody response to herpes simplex virus (HSV) in patients undergoing acyclovir treatment is reduced and, although the exact mechanism is not clear, some authors interpret it as immunosuppression. In order to clarify the mechanism, we cutaneously infected mice with HSV-1 and treated the resulting skin lesions with acyclovir. The immune response to infection and treatment in these mice was then analysed. Acyclovir treatment was given orally (20 mg/kg, three times daily), starting on day 0 (D0), 2 (D2) or 4 (D4) after infection and continuing until day 10. The serum antibody titre and the severity of skin lesions were significantly higher in the shortest treatment group (D4) than in the longer treatment groups (D0 and D2). In contrast, a skin test analysing delayed-type hypersensitivity (DTH) to HSV antigen showed that the D0 and D2 groups exhibited stronger DTH than the D4 group. Acyclovir treatment failed to cause a dissociation between DTH and antibody production in mice immunized with inactivated HSV antigen. However, acyclovir treatment in infected mice suppressed the development of skin lesions and resulted in a dissociation between DTH response and antibody production, indicating a typical immune deviation. This was supported by a change in the ratio of the isotype antibody IgG2a to IgG1. The treatment of skin lesions with acyclovir reduced the level of antibody response, as observed clinically. This indicates that the reduced antibody response in patients treated with acyclovir may be, at least in part, due to immune deviation and not immunosuppression.

Acyclovir↗

Z-335, a thromboxane A2 receptor antagonist, suppresses the progression of arachidonic acid-induced hind limb gangrene in rats.

We have developed a new rat model of gangrenous peripheral vascular disease with vascular injury and occlusive thrombi. Rat hind limb gangrene was induced by injecting arachidonic acid (2 mg/leg) into the femoral artery. Using this model, we evaluated the effect of a thromboxane A2 receptor antagonist, Z-335, on the progression of hind limb gangrene. Z-335 (10 mg/kg/d, p.o.) ameliorated arachidonic acid-induced hind limb gangrene. In contrast, daltroban (10 mg/kg/d, p.o.) and cilostazol (100 mg/kg/d, p.o.) tended to improve the hind limb gangrene but their effects failed to reach statistical significance. Z-335 (10 mg/kg, p.o.) inhibited U-46619-induced, but not collagen-induced, platelet aggregation in rat whole blood. Daltroban (10 mg/kg, p.o.) showed a tendency to inhibit U-46619-induced platelet aggregation. Cilostazol (100 mg/kg, p.o.) did not inhibit U-46619- or collagen-induced platelet aggregation. Histopathological examination of the injured paws showed that Z-355 (10 mg/kg, p.o.) had partly inhibited the formation of occlusive thrombi. These results indicate that the thromboxane A2 receptor antagonist Z-335 is effective against arachidonic acid-induced hind limb gangrene in rats. Our experiments suggest that Z-335 may be beneficial in the prevention of gangrenous peripheral vascular disease.

Animals↗

Arachidonic acid-induced hind limb gangrene: a new experimental rat model of peripheral vascular disease.

The purpose of this study was to investigate the characteristics of arachidonic acid-induced peripheral vascular disease in rats. Injecting arachidonic acid (2 mg/leg) into the femoral artery caused hind limb gangrene. Histopathological examination revealed occlusive thrombi and marked vascular injury, including denudation of the endothelium and degeneration of the media in the paw arteries. Arachidonic acid injection markedly enhanced the platelet response to both U-46619 and collagen. Although the number of circulating platelets did not differ between sham-operation rats and arachidonic acid-injected rats, the numbers of circulating white blood cells and red blood cells were raised 10 d after arachidonic acid injection. Thrombocytopenia, induced before arachidonic acid injection, markedly suppressed arachidonic acid-induced hind limb gangrene in rats. In addition, the combined administration of aspirin (100 mg/kg/d, p.o.) and ticlopidine (300 mg/kg/d, p.o.) prevented the progression of arachidonic acid-induced hind limb gangrene. These results suggest that platelets are involved in the progression of arachidonic acid-induced hind limb gangrene. This experimental rat model may be suitable for developing novel drugs for the treatment of peripheral vascular disease.

Animals↗

[Effect of liver hydrolysate on hepatic proliferation in regenerating rat liver].

The effect of liver hydrolysate (LH) derived from bovine liver on rat liver regeneration after partial hepatectomy (PH) were investigated. Oral administration of LH increased rat liver weight dose-dependently at 24 h after PH. Hepatic ornithine decarboxylase (ODC) activity and proliferating cell nuclear antigen (PCNA) labeling index were measured in regenerating rat liver as markers of cell proliferation. ODC activities at 4 and 24 h after PH were significantly increased by LH administration. PCNA labeling index at 24 h after PH were also increased by LH administration. These results suggest that LH stimulates liver regeneration in partially hepatectomized rats.

Animals↗

Increased cardiovascular and metabolic tolerance to acute hypoxia in the rat with increased hemoglobin-O(2) affinity induced by Na-cyanate treatment.

Cyanate derivatives such as NaOCN have been known to increase the hypoxia tolerance of animals by increasing the affinity of hemoglobin (Hb) to O(2). To clarify the mechanism of this increase in hypoxia tolerance, we examined changes in metabolic rate and cardiovascular parameters during a hypoxia test in halothane-anesthetized, NaOCN-treated and spontaneously breathing rats (50 mg/kg/d S.C., 10 d). Control animals received saline. The capillary density in the skeletal muscle (sternocleidomastoid muscle), cardiac papillary muscle and medulla oblongata was also examined histologically. The Hb-O(2) affinity index, P(50), decreased from 38 (control rat) to 24 mmHg in NaOCN-treated rats. During hyperoxic gas breathing, the rat treated with NaOCN showed a significantly lower metabolic rate (V(.)O(2), V(.)CO(2)), higher cardiac stroke volume, slower heart rate, lower PvO(2), and lower O(2) extraction ratio than those in control rats. The NaOCN-treated rats exhibited well-maintained arterial blood pressure and a larger cardiac output response to reduction in FIO(2) to 0.10-0.08. The increase in O(2) extraction ratio with reduction in FIO(2) was larger in NaOCN-treated than in control rats. The circulatory and metabolic depressions at FIO(2) 0.05 were effectively attenuated in NaOCN-treated rats. The capillary density of the cardiac muscle and medulla oblongata but not the skeletal muscle was significantly higher in NaOCN-treated rats than in control rats. The greater hypoxia tolerance in NaOCN-treated rats is ascribed to the combined effects of left shift of Hb-O(2) dissociation curve, lower basal V(. )O(2), higher capillary density in the heart, and brain, and other adaptive mechanisms induced probably by prolonged tissue hypoxia.

Acute Disease↗

Effect of ion transport inhibitors and methacholine on short-circuit current of isolated guinea pig nasal epithelium.

To clarify the ion/water secretion mechanism in the nasal epithelial cells, the Ussing chamber method was applied to the nasal mucosa isolated from guinea pigs. The preparation, which contained surface epithelial cells, showed a small but consistent potential difference between mucosal and submucosal sides (mucosal surface negative to submucosa). The short-circuit current (Isc) across the epithelial layer was measured, and the effects of Na+ and/or Cl- transport inhibitors and methacholine (MCh) on Isc were analyzed. The basal Isc was almost totally suppressed by the combined application of amiloride (Na+ transport inhibitor) and low-Cl- Krebs Ringer (KR) solution or solutions containing Cl- transport inhibitors (furosemide or DPC). The application of MCh elicited triphasic Isc responses, i.e., initial transient increase (phase 1) followed by a small decrease (phase 2) and further sustained increase (phase 3) in Isc. A possible ionic mechanism underlying phase 1 and 3 responses was analyzed. The Phase 1 response was greatly reduced by low-Cl- KR solution or furosemide but not influenced by amiloride. The Phase 3 response was augmented by amiloride and suppressed by low-Cl- KR solution, furosemide or DPC. These findings indicated that the basal Isc was associated with Cl- secretion and/or Na+ absorption across epithelial cells under short-circuit condition and that MCh increased Isc probably via enhancing Cl- secretion in the nasal surface epithelial cell.

Amiloride↗

[Epidemiological study for infection with H. pylori in Japan compared with that in USA, Europe and Asian Pacific area].

The prevalence of infection with H. pylori in developed countries was about 20%, on the other hand in developing countries it reached over 80%. In developed countries 40% of infants already had anti-H. pylori antibody and the prevalence of infection rapidly increased and then reached the peak (80%) in teenager. In contrast in developed countries the rate of infection with H. pylori was below 20% in teenager and gradually increased by age (1% per 1 year). In our country an unique pattern of the prevalence of infection with H. pylori was observed. The rate of infection with H. pylori in young person was low and increased with 1% per 1 year (developed countries pattern). However, middle-aged person had higher rate of infection of H. pylori (over 85%) (developing countries pattern). These results suggested H. pylori infection would be closely associated with childhood living conditions than current living (including socioeconomic) status. From this point of view, the prevention for infection with H. pylori in childhood will be most important to prevent the gastroduodenal disease related with H. pylori in the future.

Adolescent↗

[History of the treatment of Helicobacter pylori and clinical efficacy].

The combination of a proton pump inhibitor with antibiotics has been accepted as an effective treatment for the eradication of Helicobacter pylori and the most rational regimen to cure peptic ulcers. Triple therapies including two antibiotics and a proton pump inhibitor achieves constant and high eradication rate. The one-week, low-dose triple regimen including metronidazole has been accepted in European countries, but the new triple therapy with proton pump inhibitor, amoxicillin and clarithromycin is recommended for treatment of H. pylori infection in Japan. Quadruple therapy with two antibiotics, bismuth and a proton pump inhibitor is a second-line therapy. Triple therapy with ranitidine bismuth and two antibiotics may be promising.

Anti-Bacterial Agents↗

[Unruptured aneurysm of the right sinus of Valsalva: a case report].

A previously healthy and asymptomatic 45-year-old woman was referred for evaluation of a heart murmur and an unusual dilatation in the aortic root. Transthoracic and transesophageal echocardiography, computed tomography, magnetic resonance imaging, and cardiac catheterization revealed an aneurysm with a maximum diameter of 6.0 cm in the right sinus of Valsalva. Aortic regurgitation and stenosis at the right ventricle outflow tract were associated with the aneurysm. Surgery and histological study demonstrated that the sinus of Valsalva aneurysm was enormously dilated with idiopathic degenerative change in the aortic media. The aneurysm was tremendously large compared to any previously reported. Decrease in pressure load during diastole caused by aortic regurgitation probably resulted in the growth of this huge aneurysm without rupture.

Aortic Aneurysm↗

Comparative genomic hybridization of squamous cell carcinoma of the esophagus: the possible involvement of the DPI gene in the 13q34 amplicon.

We investigated copy number aberrations in 29 primary tumors and 12 cell lines of esophageal squamous cell carcinoma (ESC) using comparative genomic hybridization. In the primary tumors, the most common sites of copy number gains were 3q26.3-27 (45%), 8q24 (41%), 5p15 (38%), Xq27-28 (38%), 14q32 (31%), 11q13 (28%), and 20q13.3 (28%). High-level gains (HLGs) indicative of gene amplifications were identified at 11q13 in two cases, and in one case each at 2q33-34, 3q25-29, 5p15.1-15.2, 7q21-22, 11p11.2, 12p11.2-12, and 13q34. Recurrent losses were observed only at 9p13(17.2%). In the 12 ESC cell lines, the most common sites of HLGs were 5p15.1-15.3 (four cases), 11q13 (four cases), 8q24.1-24.2 (three cases), 20q13.2-13.3 (three cases), 3q26.3 (two cases), and 7p15-22 (two cases). Less frequent HLGs (one case each) were observed at 2p16-22, 3q25, 7p12-14, 7q21-22, 9q34, 10q21, 11p11.2, 14q13-14, 14q31-32, 15q22-26, and 17p11.2. Chromosomes and chromosome arms that showed frequent losses in the cultured lines were 18q (58%), 4 (50%), 9p (50%), and 3p (42%). These findings provide evidence for a number of previously unknown genomic aberrations in ESC, suggesting target regions for positional cloning of genes relevant to carcinogenesis in the esophagus. In particular, we identified a significant amplification of the DPI gene (TFDPI), a transcription factor that forms heterodimers with E2FI, in the single primary tumor that exhibited HLG at 13q34.

Blotting, Southern↗

Fatal liver failure in haemophiliacs with HIV-induced immunodeficiency: observation of six patients.

We observed six cases of haemophiliacs with HIV-induced immunodeficiency who died from fatal liver failure despite the absence of evident cirrhosis. They all had the infection with hepatitis viruses (two patients with hepatitis B and D viruses and four patients with hepatitis C virus) and their CD4 counts were severely decreased. They were much younger than cirrhotic haemophiliacs without HIV. Their serum levels of hyaluronic acid and type IV collagen were lower than those in haemophiliacs with cirrhosis, and were normal. No patients had experienced symptoms or concomitant diseases characteristic of cirrhosis, such as ascites, jaundice, oesophageal/gastric varices or hepatocellular carcinoma, except for one case who had a history of mild ascites. The characteristics of this liver failure were different from liver failure resulting from cirrhosis caused by chronic hepatitis, which suggests liver failure that is specific to patients with immunodeficiency. This kind of liver failure can be a factor threatening survival in patients with HIV infection and with hepatitis virus co-infection in an immunodeficient state.

Acquired Immunodeficiency Syndrome↗

Non-suture end-to-end anastomoses between polytetrafluoroethylene graft and vessels for blood access.

BACKGROUND: Non-suture end-to-end anastomoses between polytetrafluoroethylene grafts and blood vessels were achieved using absorbable cuff material in experimental and clinical studies. The cuff was made of a synthetic biodegradable material, a lactic-glycolic acid copolymer, similar in composition to conventional absorbable surgical sutures. METHODS: In the experimental study, vascular anastomoses for prosthetic interposition of the infrarenal aorta in rabbits were created using the cuff method. Six months after surgery, the cuff anastomoses sites were examined angiographically and microscopically and found to be patent and smooth without neointimal hyperplasia. RESULTS: The cuff layer had been completely absorbed. The clinical application used a similar technique and involved the creation of forearm bridge graft fistula in twelve patients for hemodialysis. In eight patients, Doppler fistula flow rate ranged from 167 ml/min to 392 ml/min. Ten of the twelve patients continued dialysis uneventfully. The one-year patency rate was 78% (7/9). The longest patency period was 920 days and the graft access continued to maintain sufficient blood flow for hemodialysis. CONCLUSIONS: This absorbable cuff material is therefore well suited for the construction of prosthetic vascular end-to-end anastomoses.

Aged↗