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Biomedical subjects

M Kitagawa

Publications and source records attributed to M Kitagawa.

At least 181 records · Page 10Linked to original sources

Percutaneous long-term arterial access with implantable ports. Direct subclavian approach with US.

PURPOSE: To clarify the clinical feasibility of getting a long-term arterial access at the subclavian region by directly puncturing the artery under ultrasound guidance. MATERIALS AND METHODS: Percutaneous placements of arterial infusion catheters with implantable ports were performed in 30 patients with malignant abdominal tumors. The axillary artery in the subclavian region was punctured directly with an 18G needle under ultrasound guidance. Using the Seldinger technique, a 5Fr catheter was placed with its tip in the hepatic or the other tumor-supplying arteries. The catheter was connected to an implantable port, and both of them were embedded in the subcutaneous pocket. RESULTS: Percutaneous placements of infusion catheters were successfully performed in 29 cases. Transarterial chemotherapy through implanted ports was done uneventfully in 26 patients, while in the other three cases, catheter dislodgment occurred. Two local haematomas, one wound infection and one cerebellar infarction were also experienced. CONCLUSION: Ultrasound-guided subclavian approach is a minimally invasive way of implanting an infusion catheter for chemotherapy, although its indication for severely atherosclerotic patients should be limited.

Abdominal Neoplasms↗

Localization of Fas and Fas ligand in bone marrow cells demonstrating myelodysplasia.

Frequent apoptosis in the bone marrow of patients with myelodysplastic syndromes (MDS) was demonstrated on frozen sections using the terminal deoxytransferase (TdT)-mediated dUTP nick end labeling (TUNEL) method. The overall mean percentage of TUNEL-positive cells was about 17% in the bone marrow of MDS, while bone marrow from control cases exhibited a mean of 3.4% (P < 0.001). To elucidate the mechanism of apoptosis in bone marrow cells of MDS, the expression of Fas antigen and Fas ligand (FasL) was examined by RT-PCR and immunohistochemistry. All MDS cases showed expression of Fas mRNA (12/12) and most exhibited an expression of FasL mRNA (10/12) by RT-PCR. Basically, control cases did not show positive signals for Fas and FasL mRNA, however, a very weak band was detected in three cases (3/10) for Fas and in one case (1/10) for FasL mRNA by RT-PCR. Immunohistochemical examination revealed positive staining for Fas (11/12) and FasL (12/12) in the bone marrow of MDS, while all the bone marrow samples from control cases were negative for anti-Fas (0/15) and for anti-FasL (0/15) antibody. Double staining clarified that TUNEL-positive apoptotic cells expressed Fas antigen on the cell surface, although not all Fas-positive cells were TUNEL positive. The Fas-positive cells of MDS bone marrow included hematopoietic cells expressing CD34 antigen, neutrophil elastase, a marker for myeloid series of cells, or glycophorin A, a marker for erythroid cells. However, CD68-positive cells which were macrophage lineage cells, did not express Fas antigen strongly. In contrast, positive staining for FasL was detected in hematopoietic cells and CD68-positive cells in the bone marrow of MDS. These results suggest that the Fas-FasL system plays an important role in inducing apoptosis in the bone marrow of MDS and works in an autocrine (hematopoietic cell-hematopoietic cell interaction) and/or paracrine (hematopoietic cell-stromal cell interaction) manner.

Adult↗

Heat shock regulation in the ftsH null mutant of Escherichia coli: dissection of stability and activity control mechanisms of sigma32 in vivo.

The heat shock response of Escherichia coli is regulated by the cellular level and the activity of sigma32, an alternative sigma factor for heat shock promoters. FtsH, a membrane-bound AAA-type metalloprotease, degrades sigma32 and has a central role in the control of the sigma32 level. The ftsH null mutant was isolated, and establishment of the DeltaftsH mutant allowed us to investigate control mechanisms of the stability and the activity of sigma32 separately in vivo. Loss of the FtsH function caused marked stabilization and consequent accumulation of sigma32 ( approximately 20-fold of the wild type), leading to the impaired downregulation of the level of sigma32. Surprisingly, however, DeltaftsH cells express heat shock proteins only two- to threefold higher than wild-type cells, and they also show almost normal heat shock response upon temperature upshift. These results indicate the presence of a control mechanism that downregulates the activity of sigma32 when it is accumulated. Overproduction of DnaK/J reduces the activity of sigma32 in DeltaftsH cells without any detectable changes in the level of sigma32, indicating that the DnaK chaperone system is responsible for the activity control of sigma32 in vivo. In addition, CbpA, an analogue of DnaJ, was demonstrated to have overlapping functions with DnaJ in both the activity and the stability control of sigma32.

ATP-Dependent Proteases↗

Postnatal development of Eustachian tube: a computer-aided 3-D reconstruction and measurement study.

The postnatal development of the Eustachian tube (ET) and its surrounding structures was investigated by means of computer-aided three-dimensional (3-D) reconstruction methods in 13 normal human temporal bones, obtained from individuals 3 months to 71 years old. The cross-sectional area, width and height of the lumen in most of the cartilaginous portion of the ET were significantly smaller in children than in adults. In particular, there was a marked, age-associated difference in the shape of the lumen in the cartilaginous portion of the ET. In adults, the cross-sectional area of the lumen declined monotonically between a large opening at the pharyngeal orifice and the narrowest portion of the ET (near the border of the cartilaginous and junctional regions). In children, by contrast, the ET lumen was uniformly smaller over the first 80% of its length from the pharyngeal orifice. It is suggested that this immature morphology of the ET lumen may confer increased risk of developing otitis media during childhood.

Adolescent↗

Pharmaceutical development for treating pancreatic diseases.

The efficacy of medications to treat pancreatic diseases, even when proven effective by experimental studies, are difficult to prove by controlled clinical trials. In the treatment of acute pancreatitis, prophylactic antibiotics, somatostatin, protease inhibitors, and cholecystokinin (CCK)-receptor antagonists are advocated for use in the early stages of acute pancreatitis, but the data are insufficient to mandate prophylaxis use or recommend their use as a standard of care. In the treatment of chronic pancreatitis, digestive enzymes, oral active protease inhibitors, CCK-receptor antagonists, or somatostatin are administered for pain relief. Extracorporeal shock-wave lithotripsy and oral dissolution therapy with trimethadione are used to treat pancreatic stones. The goals of treatment of acute pancreatitis should be to ameliorate the severity of pancreatic inflammation or to prevent its complications. Although several treatments seem to be promising from the studies reviewed, these medications require prospective comparison with the standard procedures and long-term evaluation.

Acute Disease↗

Effects of a new cholecystokinin antagonist, TS-941, on experimental acute pancreatitis in rats.

The effects of a new benzodiazepine-derivative, cholecystokinin receptor antagonist, TS-941, on experimental acute pancreatitis were studied in rats. Hemorrhagic pancreatitis was induced by an infusion of a mixture of trypsin and taurocholate into the pancreatic duct. Edematous pancreatitis was induced by intraperitoneal injection of 40 microg/kg body weight of cerulein at 0 and 1 h after the start of the experiment. TS-941 (3 mg/kg) was injected subcutaneously immediately and 3 h after the induction of pancreatitis. In trypsin-taurocholate-induced pancreatitis, TS-941, with or without the synthetic trypsin inhibitor ONO-3403, had no beneficial effects on the survival rate, pancreatic wet weight, and serum pancreatic enzymes. In cerulein-induced pancreatitis, the treatment with TS-941 significantly reduced the increases of pancreatic wet weight and serum amylase and lipase. Plasma trypsinogen activation peptide (TAP) significantly rose 1 h after the first injection of cerulein. TS-941 inhibited the liberation of TAP in cerulein-induced pancreatitis. These results show that TS-941 is effective for prevention of cerulein-induced edematous pancreatitis. ONO-3403 has beneficial effects on trypsin-taurocholate-induced hemorrhagic pancreatitis, but the combination of TS-941 and ONO-3403 has no additive effect.

Acute Disease↗

Holmium:YAG laser resection of the prostate versus visual laser ablation of the prostate and transurethral ultrasound-guided laser induced prostatectomy: a retrospective comparative study.

BACKGROUND: Transurethral resection of the prostate (TUR-P) is the gold standard for treating symptomatic benign prostatic hyperplasia (BPH) despite some perioperative morbidity. As a minimally-invasive alternative to TUR-P, a neodymium:YAG laser, and more recently a holmium:YAG laser, have been used in transurethral surgery for BPH. In order to assess the safety and efficacy of various BPH treatments, the outcome in patients treated with transurethral ultrasound-guided laser induced prostatectomy (TULIP), visual laser ablation of the prostate (VLAP) and holmium:YAG laser resection of the prostate (HoLRP) were retrospectively compared. METHODS: From May 1995 to August 1996, 60 patients with symptomatic BPH underwent TULIP (n=20), VLAP (n=20), and HoLRP (n=20). All patients were evaluated preoperatively and at 1 and 3 months postoperatively by the International Prostate Symptom Score (IPSS), the IPSS quality-of-life score (QOL), maximum flow rate (MFR), prostate volume, and residual urine volume. RESULTS: The preoperative mean IPSS was 18.5, 19.3, and 19.6 and the mean MFR was 6.3, 6.9, and 6.1 mL/sec in the TULIP, VLAP, and HoLRP groups, respectively. At 1 month after surgery, the mean IPSS was 10.2, 9.5, and 4.7 and the mean MFR was 9.6, 13.4, and 18.7 mL/sec while at 3 months the mean IPSS was 6.2, 6.1, and 3.6 and the mean MFR was 14.1, 16.0, and 21.5 mL/sec in patients treated with TULIP, VLAP, and HoLRP, respectively. No serious complication occurred in any patient. CONCLUSION: Although HoLRP requires expertise, it appears to be a promising treatment modality for BPH.

Aged↗

An immunohistochemical study of cadherin 5 (VE-cadherin) in vascular endothelial cells in placentas with gestosis.

OBJECTIVE: To evaluate vascular endothelial-cell functioning in placentas with gestosis, using the monoclonal antibody to cadherin 5. METHODS: The extra-cellular moiety of cadherin 5 was transfected into L-cells to enable us to examine their cell-adhesion activity. The expression of cadherin 5 was evaluated in human umbilical-vein endothelial cells and in placentas with gestosis by immunostaining using the anti-cadherin 5 antibody. A microspectrophotometric study also was conducted of the placentas with gestosis. RESULTS: We determined the total base sequence for cadherin 5 and found that it is homologous with a known cadherin but is a new, unique clone. Cadherin 5 has cell-adhesion activity and is expressed in endothelial cells at the cell-adhesion surface. The expression of cadherin 5 in endothelial cells took place in the placentas with gestosis, but to a lesser extent than in normal placental endothelial cells. CONCLUSIONS: The reduced expression of cadherin 5 in placentas with gestosis suggests that endothelial cell functioning is impaired in placentas with gestosis. Cadherin 5 in endothelial cells might influence placental functions and fetal development.

Amino Acid Sequence↗

Chaperone coexpression plasmids: differential and synergistic roles of DnaK-DnaJ-GrpE and GroEL-GroES in assisting folding of an allergen of Japanese cedar pollen, Cryj2, in Escherichia coli.

Plasmids that can be used for controlled expression of the DnaK-DnaJ-GrpE and/or GroEL-GroES chaperone team were constructed in order to facilitate assessment of the effects of these chaperone teams on folding or assembly or recombinant proteins in Escherichia coli. A typical pACYC184-based plasmid which was obtained could express the major DnaK-DnaJ-GrpE and GroEL-GroES chaperone teams from separate promoters when L-arabinose and tetracycline, respectively, were added in a dose-dependent fashion. The model protein used to determine whether this system was useful was an allergen of Japanese cedar pollen, Cryj2, which was unstable when it was produced in E. coli K-12. The effects of chaperone coexpression on the folding, aggregation, and stability of Cryj2 were examined in the wild type and in several mutant bacteria. Coexpression of the DnaK-DnaJ-GrpE and/or GroEL-GroES chaperone team at appropriate levels resulted in marked stabilization and accumulation of Cryj2 without extensive aggregation. Experiments performed with mutants that lack each of the chaperone proteins (DnaK, DnaJ, GrpE, GroEL, and GroES) or heat shock transcription factor sigma 32 revealed that both chaperone teams are critically involved in Cryj2 folding but that they are involved in distinct ways. In addition, it was observed that the two chaperone teams have synergistic roles in preventing aggregation of Cryj2 in the absence of sigma 32 at certain temperatures.

Allergens↗

Dietary fatty acids are possible key determinants of cellular retinol-binding protein II gene expression.

We previously found that dietary unsaturated fatty acids increase cellular retinol-binding protein type II (CRBP II) mRNA and its protein levels in rat jejunum. To obtain insight into mechanisms for its gene induction, we investigated the effect of depletion of dietary fat on CRBP II mRNA levels and we further examined whether dietary retinol is necessary for dietary fat-induced CRBP II gene expression. Feeding the fat-free diet, which contained a sufficient amount of vitamin A, repressed CRBP II mRNA accumulation by 50% within 1 day, and this low level was sustained over the next 9 days. Parallel to the decreased CRBP II mRNA level, the peroxisomal proliferator-activated receptor-alpha (PPAR-alpha) mRNA level in rat jejunum was decreased by long-term (7 days) feeding of an isocaloric low-fat diet compared with the control. Oral administration of corn oil in the animals fed vitamin A-free diet elicited approximately threefold accumulation of CRBP II mRNA within 6 h. However, the administration of 9-cis-retinoic acid brought about no accumulation of CRBP II mRNA. Even when rats were vitamin A-deficient, oral administration of corn oil, but not 9-cis-retinoic acid, caused an increase in jejunal CRBP II mRNA level. These results suggest that CRBP II gene expression in rat jejunum may be regulated predominantly by dietary fatty acids but little by dietary retinoids.

Alitretinoin↗

Expression of VCAM-1 in lymphocytes during the process of apoptosis.

The administration of corticosteroids induced apoptosis of thymocytes in vivo. Among various adhesion molecules examined, vascular cell adhesion molecule-1 (VCAM-1, CD106) was shown to be strongly expressed in these apoptotic cells. Flow cytometric analysis also showed the expression of VCAM-1 in apoptotic thymocytes. An RT-PCR study demonstrated the expression of VCAM-1 mRNA in thymocytes. Splenic lymphocytes and other lymphoid cell lines also expressed VCAM-1 during the process of apoptosis. VCAM-1 mRNA expression was also observed in RT-PCR performed on these cell lines.

Animals↗

Synthesis and antihypertensive activity of 4-(diazabicyclo[4.1.0]-heptenyloxy)benzopyran derivatives and their analogues.

A series of 3,4-dihydro-3-hydroxy-4-[(5-oxo-3,4-diazabicyclo[4.1.0]hept- 2-en-2-yl)oxy]-2H-1-benzopyrans and their analogues were synthesized and evaluated on potassium channel opening and hypotensive activities. Compound (-)-13B with a (4-methyl-5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yl)oxy group for the 4-position of the benzopyran ring was 3 times as potent as EMD 57283 (II), the lead compound, in hypotensive activity. The results would demonstrate that 5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yloxy moieties are effective as the substituents at the 4-position of benzopyran-type potassium channel openers.

Animals↗

Islet cell tumor in von Hippel-Lindau disease.

We describe a 42-year-old man with von Hippel-Lindau disease and islet cell tumor of the pancreas. He had retinal and cerebellar hemangioblastomas. His sister had pheochromocytoma. A pancreatic tumor was detected by ultrasonography at his periodical medical checkup. Contrast enhanced computed tomography and abdominal angiography revealed a hypervascular tumor in the pancreatic head. Histological examination of the resected tumor revealed characteristics of islet cell tumor of the pancreas, which was positive for chromogranin-A, S-100 protein, and pancreatic polypeptide, but was negative for insulin, gastrin, glucagon, somatostatin, vasoactive intestinal peptide, serotonin, and adrenocorticotropic hormone.

Adenoma, Islet Cell↗

Urinary excretion of pancreatic stone protein in diabetic nephropathy.

Urinary pancreatic stone protein (PSP) levels were measured in 68 diabetic patients and 170 healthy controls to investigate the relationship between the progression of diabetic nephropathy and PSP excretion. Urinary albumin, N-acetyl-beta-glucosaminidase (NAG), alpha1-microglobulin, creatinine clearance, and the blood PSP level were also determined in the diabetic patients. The urinary glucose level and glycemic control did not influence the urinary PSP level. In patients with normoalbuminuria (urinary albumin <20 mg/gCr, n=31), microalbuminuria (20-200 mg/Cr, n=19), and macroalbuminuria (>200 mg/gCr, n=18), the mean urinary PSP level was 347, 507, and 860 microg/gCr, respectively. These levels were significantly higher than the level in normal volunteers (168 microg/gCr, p<0.01). A significant positive correlation was observed between the urinary PSP level and the NAG or alpha1-microglobulin levels (p<0.01). There was a stronger correlation with alpha1-microglobulin. Blood PSP levels were also elevated in patients who had renal impairment with a decreased creatinine clearance. In conclusion, urinary PSP excretion was increased from the initial stage of diabetic nephropathy and this increase became more marked as nephropathy progressed. Increased PSP excretion may reflect renal tubular dysfunction.

Acetylglucosaminidase↗

CT-guided biopsy of pulmonary nodules less than 3 cm: usefulness of the spring-operated core biopsy needle and frozen-section pathologic diagnosis.

OBJECTIVE: The purpose of this study was to improve the diagnostic accuracy of CT-guided biopsy of small lung nodules with the aid of frozen-section histopathologic diagnosis. SUBJECTS AND METHODS: Since 1993, we have evaluated 52 lung nodules smaller than 3 cm with CT-guided transthoracic biopsy. Thirty-five lesions were malignant and 17 were benign. Biopsy always started with a 20-gauge spring-operated core biopsy needle. Tissue samples were sent to the pathology laboratory immediately after biopsy for histopathologic diagnosis of the frozen sections. RESULTS: In 47 (90%) of 52 lesions, sufficient material for histologic diagnosis was obtained, including 34 (97%) of 35 malignant lesions and 13 (76%) of 17 benign lesions. In the 13 benign lesions for which histologic sampling was successful, a specific diagnosis of benign was made for 10 lesions (77%). In three cases, the sample was too small to make a histologic specimen, but cytologic study using the same sample led to the correct final diagnosis: one as malignant and two as benign. In the remaining two cases, biopsy was unsuccessful. The lesions were both 1 cm in size and were found to be benign on follow-up studies. CONCLUSION: CT-guided biopsy with the aid of frozen-section specimens using small-bore spring-operated core needles is a feasible technique with good results in the histologic diagnosis of small lung lesions.

Biopsy, Needle↗

Geranylgeranylpyrophosphate plays a key role for the G1 to S transition in vascular smooth muscle cells.

Pravastatin, a HMG-CoA reductase inhibitor was found to inhibit DNA synthesis of vascular smooth muscle cells (VSMC) in a dose-dependent manner. Flow cytometric analysis demonstrated that pravastatin induced G1 arrest. Mevalonate restored the inhibitory effect of pravastatin on DNA synthesis and on cell cycle progression, suggesting the importance of mevalonate itself and/or its metabolites in VSMC proliferation. The major intermediate metabolites of mevalonate, geranylgeranyl-pyrophosphate (GGPP), farnesyl pyrophosphate (FPP) and IPP (isopentenyl pyrophosphate) were prepared in the form of liposomes, and the effects of GGPP, FPP and IPP on pravastatin induced inhibition of VSMC proliferation and G1 arrest were examined. Only GGPP restored the pravastatin-induced inhibition of DNA synthesis and G1 arrest. Pravastatin inhibited translocation of Rho small GTPase from cytosol to membrane. By the addition of GGPP, Rho small GTPase are geranylgeranylated and translocated to membranes during G1/S transition. These data suggest that GGPP, rather than FPP or IPP, is an essential metabolite among mevalonic acid metabolites for VSMC proliferation and the G1/S transition.

Animals↗

Chronic pancreatitis: overview of medical aspects.

Based primarily on our experience, we review current problems on etiology, pathogenesis, classification, diagnosis, and treatment of chronic pancreatitis. Much of the confusion and difficulty associated with chronic pancreatitis originates from the relative inaccessibility of this organ. A lack of specific and sensitive markers that are suitable for the follow-up of a long natural course of chronic pancreatitis also hinders our understanding of this disease. The resolution of the present imaging tests, even by the latest technology, is not good enough to detect early changes of the pancreas. In the past 10 years, several subgroups of patients with alcoholic and idiopathic pancreatitis have been identified based on the long-term follow-up study. Pain disappeared spontaneously in many patients during the course of the disease, but its mechanism is still poorly understood. Removal of pancreatic stones and protein plugs by chemical, endoscopic, or extracorporeal shock-wave therapy has been tried with some success, but their clinical values remain to be established. Attempts have been made to understand the etiology and pathogenesis of chronic pancreatitis at molecular levels. This approach, together with a prospective follow-up of patients, will improve our understanding on chronic pancreatitis.

Autoimmune Diseases↗