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Biomedical subjects

K Fujiwara

Publications and source records attributed to K Fujiwara.

At least 145 records · Page 8Linked to original sources

Increased expression of osteopontin in activated Kupffer cells and hepatic macrophages during macrophage migration in Propionibacterium acnes-treated rat liver.

Osteopontin is an extracellular matrix component that can act as a chemokine to induce macrophage migration. The significance of osteopontin in macrophage infiltration into the liver was examined in rats given heat-killed Propionibacterium acnes. In normal rats, osteopontin mRNA expression in the liver was minimal, determined by quantitative-competitive reverse transcription-polymerase chain reaction (RT-PCR) assay. Northern blot analysis revealed that osteopontin mRNA was not expressed in Kupffer cells isolated from normal rats. When rats received heat-killed P. acnes intravenously, marked macrophage accumulation, forming granulomas, developed in the liver later than 3 days after the injection and its extent became maximal between 5 and 7 days. In these rats, osteopontin mRNA expression was increased in the liver later than 1 day (with its peak at 3 days after the injection), and the mRNA expression was increased markedly in Kupffer cells and hepatic macrophages isolated at 7 days. The mRNA expression of monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha), chemokines for monocytes and macrophages, was also increased in the liver of P. acnes-treated rats, with peak expression at 3 days. We conclude that osteopontin derived from Kupffer cells and hepatic macrophages may contribute to the infiltration of monocytes and macrophages into the liver cooperatively with the actions of MCP-1 and MIP-1alpha in P. acnes-treated rats.

Animals↗

Autologous blood donation with recombinant human erythropoietin for abdominal aortic aneurysm surgery.

We evaluated the efficacy of autologous blood donation using recombinant human erythropoietin for elective abdominal aortic aneurysm (AAA) surgery regarding postoperative recovery. Twenty-five AAA patients who completed surgery without receiving a homologous blood transfusion were divided into two groups, consisting of a control group (n = 12) who did not bank any autologous blood, and a donation group (n = 13) who did bank more than 800 ml of autologous blood with the use of erythropoietin. The hematocrit (Ht) level of the control group decreased from 41.1% +/- 1.2% before the operation to 36.2% +/- 0.9% just afterwards (P > 0.01). In the donation group, however, the Ht did not change significantly during either the donation period or the perioperative period. The postoperative period before oral food intake and natural defecation were both significantly shorter in the donation group than in the control group. The first day of mobilization was also earlier in the donation group. In conclusion, autologous blood donation using erythropoietin for AAA surgery is therefore considered to promote the early recovery of patients.

Aged↗

The mitogenic activity of hepatocyte growth factor on rat hepatocytes is dependent upon endogenous transforming growth factor-alpha.

Both transforming growth factor-alpha (TGF-alpha) and hepatocyte growth factor (HGF) induce DNA synthesis in hepatocytes in vitro and in vivo. Hepatic and circulating levels of HGF have been reported to increase before an increase in TGF-alpha levels in several rat models of liver regeneration. In addition, serum TGF-alpha levels increase after an increase in serum HGF levels in patients with either partial hepatectomy or acute hepatitis. In this study, we investigate the significance of TGF-alpha in hepatocyte proliferation. TGF-alpha contents and DNA synthesis in cultured rat hepatocytes increased in response to HGF addition to the culture medium in a dose-related manner. These increases were suppressed by the addition of anti-sense TGF-alpha mRNA oligonucleotide. Furthermore, the addition of anti-TGF-alpha rabbit IgG suppressed the increase in DNA synthesis. When the anti-TGF-alpha antibody was administered to rats after partial hepatectomy, the number of mitotic hepatocytes was reduced in comparison to rats treated with normal rabbit IgG. These results were observed even though hepatic HGF levels were increased equally in rats given either anti-TGF-alpha antibody or normal rabbit IgG. Our results suggest that HGF stimulates TGF-alpha production in rat hepatocytes, and that the mitogenic activity of HGF depends on endogenous TGF-alpha activity.

Animals↗

Surgery for pulmonary metastases from colorectal carcinoma.

BACKGROUND: This study aims to clarify which patients would benefit by surgery for pulmonary metastases from colorectal carcinoma. METHODS: A retrospective study was undertaken in 25 patients who had undergone complete resection. In all cases, prethoracotomy carcinoembryonic antigen (CEA) level was measured and mediastinal or hilar lymph nodes were histologically examined. RESULTS: Overall 5-year survival was 39.2%. The 5-year survival rate for patients with a normal CEA level was 61.1%, as compared with 19.0% for patients with an elevated CEA level (p = 0.0423). The 5-year survival rate for patients without a lymph node metastasis was 49.5%, as compared with 14.3% for patients with a lymph node metastasis (p = 0.0032). No lymph node metastasis was a predictor of longer survival by univariate and multivariate analyses. The primary site, disease-free interval, and number and size of the metastasis were not significant prognostic factors. CONCLUSIONS: A resection for pulmonary metastasis from colorectal carcinoma is effective in patients with a normal CEA level and without a lymph node metastasis.

Adult↗

Results of preoperative mediastinoscopy for small cell lung cancer.

BACKGROUND: The significance of mediastinoscopy for small cell lung cancer is unclear owing to the small number of surgical cases. METHODS: To determine the N component of the TNM staging system, computed tomographic findings and the results of mediastinoscopy were compared with the pathologic examination of surgical specimens. RESULTS: Four cases among 37 patients (10.8%) were determined as inoperable by mediastinoscopy because of mediastinal lymph node metastasis. A thoracotomy was performed in 33 patients. Six patients (18.2%) who had been judged to have no metastasis by mediastinoscopy were found to have N2 disease after examination of the surgical specimens. In the identification of all mediastinal metastases, mediastinoscopy was 40.0% sensitive, 100% specific, and 83.8% accurate. When the superior mediastinal, paratracheal, pretracheal, tracheobronchial, and subcarinal lymph nodes were defined as approachable nodes, mediastinoscopy was 66.7% sensitive, 100% specific, and 94.6% accurate in the evaluation of these restricted nodes. Four cases among 8 patients with cN1 lesions resulted in a designation as pN2. CONCLUSIONS: Mediastinoscopy is useful for the diagnosis of an approachable mediastinal lymph node in small cell lung cancer cases. This exploration is necessary for patients with small cell lung cancer who are diagnosed as cN1 before thoracotomy.

Adult↗

Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats.

Free radicals and lipid peroxide (LPO), easily formed in the diabetic state, play an important role in the development of diabetic complications. Potentially, nicorandil may reduce the production of free radicals and LPO in various organs. In fact, increased LPO levels in the serum, kidney, and cardiac muscle of diabetic (DM) rats were reduced by nicorandil treatment (N treatment). Xanthine oxidase (XOD), which produces free radicals, was decreased in the liver and increased in the kidney of DM rats compared with control rats, and these changes were prevented by N treatment. The concentration of Cu, Zn-superoxide dismutase (SOD) decreased in the cardiac muscle and increased in the kidney of DM rats, and these changes returned to normal after N treatment. The decreased concentration of Mn-SOD in the liver, kidney, and cardiac muscle from DM rats was also reversed by N treatment. The changes in catalase and glutathione peroxidase (GSH-PX) activities in DM rats were not improved effectively by N treatment. Another K-adenosine triphosphate (K-ATP) channel opener, tilisolol hydrochloride, had an effect similar to that of nicorandil. The effects of nicorandil and tilisolol were studied only in DM rats. These data imply that N treatment, as an antioxidative therapy, may be beneficial in preventing diabetic complications due to lipoperoxidation and free radicals in DM rats.

Animals↗

Neoadjuvant chemotherapy by transcatheter arterial infusion method for uterine cervical cancer.

PURPOSE: The effects of transcatheter intraarterial infusion of anticancer drugs on the prognosis of cervical cancer were retrospectively studied. MATERIALS AND METHODS: Two or three sessions of transcatheter arterial infusion therapy were performed in 97 patients with primary uterine cervical cancer. The number of patients in stage I, II, III, or IV were 15, 37, 34, and 11, respectively. The drugs infused were cisplatin (60-70 mg/m2), doxorubicin hydrochloride (30-40 mg/m2), mitomycin (15 mg/m2), and 5-fluorouracil (500 mg/body). They were infused via the bilateral internal iliac arteries. Seventy-five patients of the 97 (78%) underwent radical hysterectomy after arterial infusion: stage I (14 of 15), stage II (31 of 37), stage III (25 of 34), and stage IV (5 of 11). Three stage II and nine stage III patients received radical radiation therapy. The other 10 patients (one with stage I, three with stage II, and six with stage IV) did not receive an operation and radiation therapy after arterial infusion because of their distant metastases at the time of operation. Thirty-eight patients of 75 (51%) received postoperative radiation therapy. RESULTS: The complete histologic response rates (no active cancer cells) after arterial infusion were four of 14, four of 31, six of 25, and one of five for stages I, II, III, and IV. The histologic response rates, which showed no parametrial invasion after arterial infusion, were 12 of 14, 24 of 31, and 15 of 25 for stages I, II, and III. The histologic response rates, which demonstrated no lymph node metastases after arterial infusion, were 12 of 14, 24 of 31, and 19 of 25 for stages I, II, and III. The overall 5-year survival rates of the patients with stages I, II, and III were 93.3%, 58.7%, and 69.7%, respectively. The 5-year survival rates of the operated patients with stages I, II, and III were 100%, 60.5%, and 63.6%, respectively. The 5-year survival rates of the irradiated patients with stage III was 87.5%. Leukocytopenia and thrombocytopenia occurred as an acute complication in 75% and 79% of the patients, respectively. As a late complication, ileus occurred in 7%. CONCLUSION: Arterial infusion may improve the prognosis of patients with cervical cancer without increasing the incidence of late complications.

Adenocarcinoma↗

Experimental study on liver regeneration after simultaneous partial hepatectomy and pancreatectomy.

In this study, we performed hepatectomy and pancreatectomy to assess the physiological contribution of the pancreas, especially in terms of endocrine function to hepatic regeneration. Group 1 Wistar rats underwent 70% hepatectomy and group 2 rats underwent 70% hepatectomy plus 50% pancreatectomy. The time course assessment of liver regeneration rates obtained by Fishback's formula demonstrated a difference in rates between the two groups as early as day 3 or day 7 after surgery. Since levels of both PCNA-positive cells and serum transforming growth factor-alpha (TGF-alpha) were significantly higher in the hepatectomy only group, we could prove the difference of liver regeneration between the two groups. We have concluded that pancreatectomy retards the liver regeneration initiation processes occurring from 24 h to 3 days after evisceration. Glucagon-insulin molar ratios most significantly differed between the two groups 3 days after evisceration in the present study. This result was due to increased glucagon level of group 2 at day 3 after evisceration. Our findings suggest that 50% partial pancreatectomy inhibits the rate of hepatic regeneration, thereby altering the supply of pancreatic hormones, especially glucagon.

Journal Article↗

PCR-SSCP analysis of 5'-nontranslated region of hepatitis A viral RNA: comparison with clinicopathological features of hepatitis A.

The recent development of the sensitive reverse transcription-polymerase chain reaction (RT-PCR) method allowed us to detect the presence of hepatitis A virus (HAV) RNA in sera from hepatitis A patients. To determine whether differences in HAV are related to the wide range of clinical severity, we used PCR-single strand conformation polymorphism (SSCP) to analyze the amplified product of the 5'-nontranslated region (5'NTR), where relatively homologous sequences are reported and the internal ribosomal entry site is considered to exist, from these various levels of hepatitis A. Twenty-seven patients admitted to Chiba University Hospital (between 1988 and 1997) were examined for HAV RNA in their sera by RT-PCR with primers located at 5'NTR of HAV RNA. The nucleotide (nt) sequence of a central part (nt 277-551) of 5'NTR was amplified and the product was examined by PCR-SSCP. HAV RNA was detected in all 27 hepatitis A patients examined: in 3 with fulminant hepatitis, 2 with severe acute hepatitis, and 22 with self-limited acute hepatitits. The amplified sequence revealed by PCR-SSCP showed that samples from fulminant and severe acute hepatitis patients had similar mobility in the gel, whereas that from acute hepatitis patients demonstrated a considerable variety in mobility patterns. From the analysis of the amplified product of 5'NTR of HAV, the bands are likely to be similar in the more severe forms of hepatitis A compared to those from uncomplicated self-limited acute hepatitis.

Acute Disease↗

Nucleotide sequence of a new Fc gamma receptor IIIB allele that codes for a neutrophil antigen.

A new allele of the human neutrophil antigen (HNA) system (tentatively called NA2M) was discovered and its nucleotide sequence was determined. NA2M differs in a single nucleotide (193G-->A) from FCGR3B*2(NA2), resulting in an amino acid change (54Glu-->Lys). The frequency of the NA2M gene in the Japanese population was estimated to be 0.008. Granulocytes of individuals possessing NA2M reacted with HNA-1b(NA2)-specific monoclonal antibody (TAG2) in the GIFT assay.

Alleles↗

The use of electrolyzed solutions for the cleaning and disinfecting of dialyzers.

Recently, the use of electrolyzed solutions has attracted considerable interest in Japan. This study investigates the efficiency of electrolyzed solutions as disinfecting agents (DA) in the reuse of dialyzers and compares their efficiency to that of other disinfectants currently in use. The following 3 methods were employed. First, the rinsing time and rebound release of reused dialyzers were measured and compared after electrolyzed solutions, electrolyzed strong acid aqueous solution (ESAAS) and electrolyzed strong basic aqueous solution (ESBAS), made from reverse osmosis (RO) water (ESAAS, ESBAS; Generating apparatuses: Super Oxseed alpha 1000, Amano Corporation, Yokohama, Japan), 2% Dialox-cj (Teijin Gambro Medical, Tokyo, Japan), and 3.8% formalin were used as DAs. This involved performing dialysis with 2 types of dialyzers: a cellulose acetate membrane (CAM) dialyzer and a polysulfone membrane (PSM) dialyzer. The dialyzers were cleaned and disinfected using the different DA and left for 48 h. Next, after performing dialysis the dialyzer membranes were cleaned with a saline solution (0.9% NaCl) and RO water and then cleaned with the various DA. These membranes were observed using a scanning electron microscope (SEM) to check for the presence of physical and biological contaminants. Finally, in vitro tests were performed to determine the level of dialyzer clearance when PSM dialyzers were reused after having been cleaned and disinfected with the electrolyzed solutions. The rinsing time results for both the CAM and PSM dialyzers showed the electrolyzed solutions (ESBAS and ESAAS) as being undetectable within 10 min. With regard to the rebound release, for both the CAM and PSM dialyzers, the electrolyzed solutions were undetectable at all checking times between 30 and 240 min. Observation by SEM showed that cleaning with both ESAAS and ESBAS left the fewest contaminants, and cleaning with 2% Dialox-cj left the highest level of contaminants in the CAM dialyzers. With regard to experiments concerning use in vitro, no major changes in the dialyzer clearance were noticed after 6 uses. In every experiment, the previous investigations showed the electrolyzed solutions to be superior to 3. 8% formalin and 2% Dialox-cj DA for the reuse of dialyzers.

Acids↗

Renal protective effect of troglitazone in Wistar fatty rats.

Although it is known that renal injury develops in obesity and diabetes mellitus, there have been no investigations examining the impact of insulin resistance per se on the development of renal injury. The present study was undertaken to examine whether insulin resistance and obesity influence urinary protein excretion (UPE) in female heminephrectomized Wistar fatty rats (WFRs). After 24 weeks of heminephrectomy in WFRs, the body weight ([BW], 465+/-18 g; n = 6), blood pressure (155+/-5 mm Hg), serum insulin to glucose ratio (1.31+/-0.39 microU/mg), and daily UPE (24+/-7 mg/d) were greater versus Wistar lean rats ([WLRs] 258+/-8 g, 134+/-1 mm Hg, 0.19+/-0.06 microU/mg, and 5+/-1 mg/d, respectively; n = 6), whereas blood glucose levels did not increase significantly. In WFRs, long-term (ie, 24 weeks) treatment with troglitazone, an insulin-sensitizing agent, improved the serum insulin to glucose ratio (0.17+/-0.09 microU/mg), reduced blood pressure (to 140+/-4 mm Hg), and decreased UPE (to 7+/-1 mg/d), although it had no effect on BW. Of note, with troglitazone treatment, the reduction in proteinuria preceded the correction of hypertension (ie, at week 12). In conclusion, our study suggests that insulin resistance per se causes proteinuria that does not appear to depend on blood pressure. Furthermore, long-term therapy with troglitazone may be a useful tool for the treatment of renal injury in the insulin-resistant condition.

Animals↗

Characterization of the renal action of pranidipine in the rat.

Although calcium antagonists elicit predominant dilation of afferent arterioles that might be associated with glomerular hypertension, there have been reported diverse observations demonstrating the effect of calcium antagonists on the progression of renal injury. The present study examined the effect of pranidipine (CAS 99522-79-9) on the renal microvascular tone in the isolated perfused hydronephrotic rat kidney, and the progression of renal insufficiency in subtotally nephrectomized spontaneously hypertensive rats. In the hydronephrotic kidney, angiotensin II caused marked constriction of both afferent and efferent arterioles. The subsequent addition of pranidipine (10 nmol/l, 100 nmol/l, 1 mumol/l) elicited dose-dependent afferent arteriolar dilation, with 97 +/- 3% reversal at 1 mumol/l. In contrast, efferent arterioles were resistant to pranidipine, with only 20 +/- 4% reversal at 1 mumol/l. In subtotally nephrectomized rats, 10-week treatment with pranidipine (3.0 mg/kg/day) markedly decreased blood pressure (from 270 +/- 6 to 158 +/- 8 mmHg) and improved renal histopathological changes, including glomerular and arteriolar sclerosis. Proteinuria was also less than than in the control rats (233 +/- 5 vs. 305 +/- 26 mg/day). Thus, although glomerular hypertension might develop as a consequence of preferential afferent arteriolar dilation, pranidipine actually improved the renal injury in subtotally nephrectomized SHR. These ostensibly discrepant observations could be attributed to the simultaneous reduction in blood pressure and the salutary actions of this agent mediated by non-hemodynamic mechanisms.

Animals↗

A long-term follow-up study of cervical lesions in rheumatoid arthritis.

To determine the natural history of cervical lesions in rheumatoid arthritis, 161 patients who had been followed for a minimum of 5 years were enrolled in this study. The average follow-up period was 10.2 years (range, 5 to 20 years). The severity of the rheumatoid arthritis was classified into three types based on the multiplicity of peripheral joint rheumatoid involvement: a least erosive subset, a more erosive subset, and a mutilating disease subset. Ninety-two patients (57%) had upper cervical involvement, which progressed in the order of anterior atlantoaxial subluxation, anterior atlantoaxial subluxation combined with vertical subluxation, and vertical subluxation alone. Subaxial subluxation was found in 18 patients (11%). In 17 of these 18 patients, upper cervical lesions were also noted. The incidence of cervical involvement in each disease subset was 39% in the least erosive group, 83% in the more erosive group, and 100% in the mutilating disease group. Fifty percent of the patients with cervical involvement had neck pain, and the remaining patients were asymptomatic. Neural involvement occurred in 10 patients. In 7 of these 10 patients, vertical subluxation of the atlas was responsible for the neural deficit. Six patients required surgical intervention because of progressive myelopathy.

Adolescent↗

Distinct action of aranidipine and its active metabolite on renal arterioles, with special reference to renal protection.

Aranidipine, a newly developed calcium antagonist, possesses unique pharmacologic characteristics in that its metabolite (M-1) still has antihypertensive action. We examined the effects of both agents on renal microcirculation using the isolated perfused hydronephrotic rat kidney. During norepinephrine-induced constriction, the addition of aranidipine dilated both afferent and efferent arterioles in a dose-dependent manner; at 10(-6) M, 83 +/- 6% and 90 +/- 6% reversal, respectively. In contrast, its active metabolite exerted dilator action predominantly on the afferent arteriole (79 +/- 4% vs. 44 +/- 17% at 10(-6) M for afferent and efferent arterioles, respectively). We further examined the long-term (8 weeks) effect of these agents on the development of renal injury in salt-loaded subtotally nephrectomized spontaneously hypertensive rats. Both aranidipine and M-1 reduced blood pressure by a similar magnitude. The decreases in proteinuria were observed in the aranidipine-treated group at weeks 6, 8, and 10, whereas in the M-1 group, significant reduction was attained only at week 6. Histopathologic examination revealed that both treatments improved glomerular and arteriolar sclerosis. Glomerular sclerosis, however, was less pronounced in the aranidipine-treated group than in the M-1 group. In conclusion, aranidipine has dilator action on both arterioles, whereas M-1 caused predominant dilation of afferent arterioles. Such metabolic changes may constitute a determinant of efferent arteriolar action of the calcium antagonist.

Animals↗

Post-scabetic nodules: a lymphohistiocytic reaction rich in indeterminate cells.

We studied six infants and two adult cases of nodular scabies with immunostains and electron microscopy. All eight cases have had either direct (KOH) or family histories of scabies and were treated with lindane 1% cream or permethrin 5% cream. Family members responded very well, but our patients developed multiple papulo-nodular lesions which were initially very pruritic and, in some cases, persisted from several months to over one year. H & E stain of biopsied tissue sections revealed a heavy perivascular and periappendageal lymphohistiocytic cell infiltration. Immunophenotype of these cells was compatible with Langerhans cells, i.e. CD1A (+), S-100 (+) and HLA-DR (+). Electron microscopy showed that these histiocytic cells satisfied all the ultrastructural criteria of Langerhans cells except for the absence of Birbeck's granules. Lag, a monoclonal antibody for Birbeck's granules, was negative. "Persistent nodules in scabies" or "nodular scabies" seems to represent a prolonged response of indeterminate cells-lymphocytes to mite antigens.

Adult↗