Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 703 records · Page 39Linked to original sources

PubMed1995

The monoclonal antibody specific for the 4-hydroxy-2-nonenal histidine adduct.

Monoclonal antibodies directed against proteins modified with the major membrane lipid peroxidation product, 4-hydroxy-2-nonenal, have been established and characterized. The monoclonal antibodies specific for HNE-modified proteins were raised by immunizing mice with a HNE-keyhole limpet hemocyanin conjugate. The resulting five monoclonal antibodies (mAbs HNEJ-1-5) recognized HNE-modified bovine serum albumin (BSA), but not native BSA in Western blot studies. Of the five mAbs, HNEJ-2 exhibited the highest affinity for HNE-modified proteins and a much higher affinity for the HNE-histidine adduct than the HNE-lysine or HNE-cysteine adducts. mAb HNEJ-2 did not cross-react with proteins that had been treated with other aldehydes, such as 1-hexenal, 2-hexenal, 4-hydroxy-2-hexenal, 2-nonenal, formaldehyde, or glutaraldehyde. These results suggest that the major epitope recognized by mAb HNEJ-2 is the Michael addition-type HNE-histidine adduct.

Aldehydes↗

PubMed1995

Acute nephrotoxicity of a carcinogenic iron chelate. Selective inhibition of a proteolytic conversion of alpha 2U-globulin to the kidney fatty acid-binding protein.

The mechanism of acute nephrotoxicity of an iron chelate in vivo has been investigated. Administration of a renal carcinogen ferric nitrilotriacetate (Fe-NTA) (15 mg Fe/kg body weight, intraperitoneally) led to selective loss of a renal protein with an apparent molecular mass of 17 kDa. Analysis of the 17 kDa protein by NH2-terminal sequence demonstrated its identity over 16 NH2-terminal residues as a kidney fatty acid-binding protein (k-FABP) that is a proteolytically modified form of alpha 2U-globulin, a major urinary protein of adult male rats. An immunochemical study using anti-alpha 2U-globulin polyclonal antibodies confirmed that a single injection of Fe-NTA led to a decrease in k-FABP levels. However, a 19-kDa protein identical to the alpha 2U-globulin progressively appeared in the kidney, suggesting that the proteolytic processing of alpha 2U-globulin in the renal proximal tubules was suppressed by the treatment with Fe-NTA. By monitoring k-FABP and its precursor alpha 2U-globulin, it was determined that repeated exposure to Fe-NTA caused suppression of both proteolytic and endocytotic activity of the kidney. The implications of these data in relation to the nephrotoxicity of Fe-NTA are discussed.

Alpha-Globulins↗

PubMed1995

Lung metastasis from parathyroid carcinoma causing recurrent renal hyperparathyroidism in a hemodialysis patient: report of a case.

We report herein the case of a 46-year-old woman on hemodialysis (HD) who developed recurrent renal hyperparathyroidism induced by lung metastasis from parathyroid carcinoma. The patient had been commenced on HD for chronic renal failure about 20 years earlier and had undergone a parathyroidectomy for advanced renal hyperparathyroidism 8 years later. After the initial operation, further explorations of the neck were performed due to recurrence, despite which the hyperparathyroidism persisted and she was finally referred to our department. The appearance of multiple coinlike lesions on a chest X-ray and computed tomography led to the diagnosis of recurrent hyperparathyroidism induced by lung metastasis from parathyroid carcinoma. A pulmonary wedge resection was performed and the metastatic parathyroid nodules were removed. Of the several hypotheses about the etiology of parathyroid carcinoma in HD patients, it is most likely that the parathyroid hyperplasia induced by chronic renal failure develops into carcinoma. Even in renal hyperparathyroidism, we should bear in mind the possibility that metastatic parathyroid carcinoma is a possible source of excess parathyroid hormone secretion at recurrence.

Carcinoma↗

PubMed1995

Senile plaques in an aged two-humped (Bactrian) camel (Camelus bactrianus).

Senile plaques with beta-protein as a major constituent are a conspicuous feature in the brains of aged humans, monkeys, dogs, and bears. We found cerebral senile plaques of the diffuse and primitive type, but not the classical type, in an aged female camel of more than 20 years old. The senile plaques and a few cortical capillaries were immunoreactive with anti-beta-protein serum. Congophilic amyloid deposition was detected in a small number of the capillaries, but not in the senile plaques. We believe this to be the first detailed report of senile plaques in a herbivore, and these findings suggest the possibility of senile plaque formation in a wide variety of mammalian species.

Aging↗

PubMed1995

Immunosuppressive drugs and their effect on experimental tumor growth.

The effect of cyclosporin (CyA), FK 506, and mycophenolate mofetil (MPM) on tumor growth was investigated using syngeneic mouse colon carcinoma 38. Mice were laparotomized and the tumor cells were injected into the portal vein to establish liver metastasis. The animals were grouped as follows: groups A-1, B-1, and C-1 were given CyA [15 mg/kg body weight (BW)], FK 506 (0.15 mg/kg BW), and MPM (100 mg/kg BW), respectively, 30 min before tumor inoculation and daily for 5 days by gavage; groups A-2, B-2, and C-2 were given CyA (30 mg/kg BW), FK 506 (0.3 mg/kg BW), and MPM (200 mg/kg BW), respectively, with the same dose timing; and groups A-3, B-3, and C-3 received CyA (30 mg/kg BW), FK 506 (0.3 mg/kg BW), and MPM (200 mg/kg BW), respectively, on the 7th post-tumor inoculation day and on the following 5 days. The mean tumor diameter in groups A-1 and A-2 was greater than that in the control group and in groups C-1 and C-2 at 3 weeks (P < 0.05). The mean tumor numbers in groups A-1 and A-2 were greater than those in the control group and in groups C-1 and C-2 at 4 weeks (P < 0.05). With in vitro MTT assay, all three drugs acted cytostatically on tumor cells with a higher concentration (10(-6)-10(-4) mol/l), while no cytostatic effect was noted with CyA at a lower concentration (10(-9)-10(-7) mol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1995

Regional myocardial function curve of the ventricle.

To understand the pathophysiology of diseased hearts, we devised a new regional myocardial function curve and investigated its properties. Regional work per unit volume of the myocardium (RWM) was calculated by integrating mean wall stress (sigma) with respect to the natural logarithm of the reciprocal of wall thickness [ln(1/H)] over a cardiac cycle. Regarding the end-diastolic ln(1/H) as the preload for the region of concern on the assumption that the myocardium is incompressible, we defined the relation between RWM and end-diastolic ln(1/H) as the regional myocardial function curve. In ten mongrel dogs, we measured left ventricular pressure, left ventricular internal diameter, and wall thickness with a catheter-tip micromanometer and ultrasonic dimension gauges during volume loading to obtain the regional myocardial function curve. We examined the sensitivity of the regional myocardial function curve to changes in contractile state (isoproterenol, propranolol) and changes in afterload (pressure loading by a balloon-occlusion catheter). The linear fit to the data points of the regional myocardial function curve under each condition always achieved a very good correlation coefficient (greater than 0.62). Isoproterenol increased the slope of the regional myocardial function curve from 9.7 +/- 0.9 (SEM) mJ/cm3 to 14.4 +/- 1.0 mJ/cm3 (P < 0.01), with no significant changes in the x-intercept, while propranolol decreased it to 5.6 +/- 1.2 mJ/cm3 (P < 0.01) with no significant changes in the x-intercept.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Protective effects of endothelin-1 on acute pancreatitis in rats.

Endothelin-1, a 21-residue peptide isolated from vascular endothelial cells, has a broad spectrum of actions. To clarify the involvement of endothelin-1 in acute pancreatitis, we examined the effects of endothelin-1 and its receptor antagonist BQ-123 on cerulein-induced pancreatitis in rats. Rats were infused intravenously with heparin-saline (control), endothelin-1 (100 pmol/kg/hr), cerulein (5 micrograms/kg/hr), or cerulein plus endothelin-1 for 3.5 hr. In another experiment, cerulein or cerulein plus BQ-123 (3 mg/kg/hr) was infused. Infusion of cerulein caused hyperamylasemia and pancreatic edema. Endothelin-1, when infused with cerulein, decreased the extent of pancreatic edema with a significant increase in the pancreatic dry- to wet-weight ratio. Histological changes induced by cerulein were markedly attenuated when endothelin-1 was given with cerulein. In contrast, endothelin-receptor blockade with BQ-123 further augmented pancreatic edema caused by cerulein. The extent of inflammatory cell infiltration was greater than BQ-123 was given with cerulein. Endothelin-1 or BQ-123 had no influence on hyperamylasemia. This study suggests that endothelin-1 has protective effects on experimental acute pancreatitis.

Acute Disease↗

PubMed1995

Iliopsoas bursa of the rheumatoid hip joint. A case report and review of the literature.

Presented is the case of a 63-year-old woman, with a 30-year history of rheumatoid arthritis, whose hip was completely destroyed and accompanied with enlargement of the iliopsoas bursa. Preoperative diagnosis was confirmed by computed tomography, magnetic resonance (MR) imaging and arthrography. She was treated by resection of the iliopsoas bursa and total prosthetic replacement of the hip joint. The pathogenesis is uncertain. In the literature, enlargement of the iliopsoas bursa with rheumatoid arthritis, osteoarthritis, pigmented villonodular synovitis, and synovial chondromatosis had been reported. Nevertheless, a correct preoperative diagnosis of the enlargement of the iliopsoas bursa is very difficult. MR imaging with enhanced Gadolinium-DTPA (Gd-DTPA) is proposed as the most useful examination for preoperative diagnosis.

Arthritis, Rheumatoid↗

PubMed1995

Nizatidine accelerates gastric emptying of a solid meal in rats.

Nizatidine, a new histamine-2-receptor antagonist, stimulates gastrointestinal motility in dogs and gastric emptying of liquids in rats. Effect of nizatidine on gastric emptying of a solid meal was investigated using a novel gastric emptying model in rats. Male Wistar rats (weighing 200-300 g) were supplied with powdered food containing 30 w/w% barium 14 hr before the beginning of the experiment and x-ray photography of rat stomach was taken under light ether anesthesia. Gastric emptying was assessed by percentage of a decrease in area 30 min after drug was injected intraperitoneally. There was a positive correlation between the area of the gastric outline and the weight of the gastric contents (r = 0.94, P < 0.01). Ether anesthesia itself did not affect gastric emptying. Nizatidine increased gastric emptying dose-dependently (emptied percentage; vehicle: 4.9 +/- 1.5%, 1 mg/kg: 7.2 +/- 0.4%, 3 mg/kg: 10.4 +/- 2.0%, 10 mg/kg: 16.7 +/- 4.9%, 30 mg/kg: 25.7 +/- 7.4%). N-Desmethyl nizatidine (NDM) also stimulated gastric emptying, but nizatidine S-oxide, cimetidine, an famotidine had no significant effects on gastric emptying. Nizatidine and neostigmine, but not NDM, at a subthreshold dose accelerated gastric emptying treated with a low dose of acetylcholine (0.1 mg/kg). Atropine (2 mg/kg, -30 min) did not modulate the gastroprokinetic action of nizatidine, but blocked that of NDM. These findings suggest that this noninvasive method may allow measurement of gastric emptying of solids accurately and that nizatidine and NDM facilitate gastric emptying probably mediated by a direct and/or an indirect (acetylcholinesterase inhibition) cholinergic mechanism.

Acetylcholine↗

PubMed1995

Effect of cold-restraint stress on immunoreactive thyrotropin-releasing hormone and immunoreactive somatostatin in the rat stomach.

The effects of cold-restraint stress on immunoreactive thyrotropin-releasing hormone (ir-TRH) and immunoreactive somatostatin (ir-SOM) concentrations in the rat stomach were investigated. Rats immobilized with a spring-loaded metallic plate were placed in a room maintained at 4 degrees C for 1-3 h and then decapitated serially for investigation. Gastric ir-TRH and ir-SOM concentrations were measured by individual radioimmunoassays. Cold-restraint stress induced gastric mucosal lesions as well as a decrease of the ir-TRH concentration in the glandular stomach, an increase of the ir-TRH concentration in the gastric juice, and a decrease in gastric pH. In contrast, this stress caused an increase of ir-SOM in the glandular stomach and a decrease of ir-SOM in the gastric juice. However, cold or restraint stress alone did not induce gastric mucosal lesions or changes in gastric ir-TRH and ir-SOM concentrations or the gastric pH. To clarify the endocrine influence of peripheral TRH, pretreatment with thyroid hormone was performed to inhibit elevation of the serum TRH level during cold-restraint stress. Despite this pretreatment, cold-restraint stress still induced ulcer formation, along with changes in gastric ir-TRH and ir-SOM concentrations and gastric pH. These findings suggest that changes in gastric ir-TRH and ir-SOM concentrations may be closely related to ulcer formation due to cold-restraint, and that TRH may act in a paracrine manner in the stomach.

Animals↗

PubMed1995

Prevention of experimental hepatic metastasis with thromboxane synthase inhibitor.

To investigate the effectiveness of thromboxane (Tx) synthase inhibitor in the prevention of experimental hepatic metastasis, an in vivo study was designed. Hepatic metastasis was brought about by injection of 1 x 10(5) cells of colon 38 tumor into the portal vein of C57 B1/65 mice. Seven groups (n = 16 in each group) received different treatments: with TxA2 synthase inhibitor (sodium ozagrel), 5, 10 or 15 mg/kg BW before tumor inoculation, and daily for the following 3 days, (groups A, B and C, respectively); with acetyl salicylic acid (aspirin), 1.0, 1.5 or 2.0 mg/kg BW (groups C, D, and E, respectively); a control group, inoculated with vehicle only. Serum TxB2, a stable metabolite of TxA2, and prostaglandin F1 alpha were measured. Labeling index for tumor proliferation by bromodeoxy-uridine radioimmuno-assay was also studied. Incidence of metastasis in groups A (60.5%), B (49.5%), C (43.0%), D (80.5%), E (66.0%) and F (58.4%) was less than that in the control group (100%). Tumor size, number of labeling index did not differ among the groups. Serum TxB2 (pg/ml) levels were significantly lower in all of the groups than in the control. Serum PGF1 alpha levels in the groups with aspirin were lower than those in sodium ozagrel. Tx synthase inhibitor is effective in the prevention of experimental hepatic metastasis when it is given before and immediately after tumor inoculation. As Tx synthase inhibitor leaves metabolic pathway to PGI2 production intact, it is more effective in the prevention of metastasis than aspirin since aspirin inhibits both thromboxane and PGI2.

Animals↗

PubMed1995

Endothelin-1 and in vitro evidence of renal artery vasoconstriction after liver transplantation.

Twelve pigs underwent orthotopic liver transplantation. The mean endothelin-1 (ET-1) levels in the serum samples of the recipient animals 1 h after reperfusion of the graft (6.2 +/- 1.5 pg/ml) was significantly higher (P < 0.05) than in pretransplantation samples (3.2 +/- 0.6 pg/ml). Serum blood urea nitrogen (BUN) 24 h after transplantation was 13.8 +/- 5.9 mg/dl, which was significantly higher than before transplantation (6.4 +/- 2.2 mg/dl). There was a positive correlation between the serum BUN and ET-1 (r = 0.62, P < 0.05). An in vitro isometric tension study was performed for the contractility response rate of the intact renal artery in the bath chamber containing the serum of the corresponding recipient animals. The mean contractility response rates were higher with the serum obtained after reperfusion of the graft (66.9 +/- 32.4%) than with those obtained before transplantation (18.3 +/- 9.2%) when compared to a standard contractility rate of 100% with 40 mM KCI. Moreover, these contractility response rates were significantly reduced (32.8 +/- 21.0%) with the addition of the ET-1 receptor antagonist FR139317. The results of the present study demonstrated that the liver transplantation was associated with elevation of ET-1 in the serum of the recipient animals. It was considered that ET-1 in the serum caused a direct vasoconstriction of the renal artery in vitro. This may help to explain the renal dysfunction that is often seen in the recipients of clinical liver transplantation.

Animals↗

PubMed1995

Transgenic neural plate contributes neuronal cells that survive greater than one year when transplanted into the adult mouse central nervous system.

Neural plate cells from the early embryo may have a number of important advantages as donor material for the delivery of foreign genes into the diseased adult central nervous system (CNS). Mesencephalic neural plate from transgenic GT4-2 mice was used as a source of marked donor cells to determine whether transgene-expressing embryonic CNS progenitor cells can be used as donor material for implantation into the adult mouse brain. Transgenic mouse embryos from this line express the Escherichia coli beta-galactosidase (beta-gal) gene throughout early CNS development. At the early somite stage (Embryonic Day 8.5), mesencephalic neural plate tissue from heterozygous embryos was dissected out and either transferred into culture for characterization or immediately implanted into the striatum or lateral ventricle of adult wild-type CD-1 mice. Explants of neural plate tissue possessed intense beta-gal activity and produced extensive outgrowth of neurofilament-positive processes after 6 days in vitro. Many beta-gal-positive cells migrated away from the explanted tissue mass. Grafts of transgenic neural plate tissue in the normal adult mouse striatum, sampled 2 weeks to 1 year after implantation, possessed healthy beta-gal-positive cells. More detailed analysis of grafts 3 months after implantation indicated that most beta-gal-positive cells were also immunoreactive for neurofilament and microtubule-associated proteins, two neuron-specific markers. In addition, extensive neurofilament-positive axonal tangles were evident within the grafts among the beta-gal-positive cells. Electron microscopic (EM) findings of implanted tissue stained with Bluo-Gal revealed many beta-gal-positive neurons received synaptic contacts from other cells. A few donor-derived astrocytes were also found in the grafts by EM analysis. No obvious signs of immunological rejection, or of significant decrease in graft volume, were observed at any age. Some beta-gal-positive cells were observed to lie up to 230 microns away from the main graft mass in both striatal and intraventricular implantations. These data suggest that the neural plate can contribute a long-surviving population of neuronal and astrocytic cells when transplanted into the adult CNS.

Animals↗

PubMed1995

Hepatitis C viral complexity detected by single-strand conformation polymorphism and response to interferon therapy.

BACKGROUND/AIMS: Hepatitis C virus (HCV) genome heterogeneity by sequence analysis in association with interferon (IFN) inefficacy has been reported. This study was performed to establish a convenient method for detecting the HCV quasispecies complexity and to determine the correlation between the complexity and the responsiveness to IFN therapy in patients with chronic hepatitis C. METHODS: The quasispecies complexity of HCV hypervariable region 1 in patients treated with IFN-alpha was analyzed by polymerase chain reaction-mediated single-strand conformation polymorphism (SSCP). RESULTS: Seven of 25 patients (28%) with low complexity (SSCP band number of < or = 2) were HCV RNA negative after treatment, whereas in 24 patients with high complexity (SSCP band number of > or = 3), the response to IFN was almost insignificant because only 1 patient (4.5%) remained HCV RNA negative after treatment (P < 0.05). Among type 1b patients, IFN therapy was only effective for patients with low amounts of HCV RNA (< or = 10(7.5) copies/mL serum) and low complexity. In contrast, most type 2a patients tended to respond to the therapy with exceptions being those with high amounts of HCV RNA and high complexity. CONCLUSIONS: The complexity of the hypervariable region 1 quasispecies may be a factor for predicting IFN inefficacy in patients with chronic hepatitis C.

Amino Acid Sequence↗

PubMed1995

Glomerular endothelial cells promote mesangial cell growth via a PDGF-Like substance.

We conducted these experiments to determine whether glomerular endothelial cells (GEN) may play a role in the regulation of glomerular mesangial cells (GMC) growth. When GMC were separately co-cultured with GEN for 24 h, [3H]thymidine incorporation into GMC increased by 22%. In addition, when GMC were co-cultured with GEN for 4 days, the GMC count increased statistically. Conditioned medium (CM) was obtained from confluent GEN monolayers and tested for its effect on GMC growth. When CM was mixed with RPMI 1640 medium containing fetal calf serum (final concentration: 10%), GMC growth was potentiated in a dose-dependent manner. This stimulatory effect of CM from GEN cultures was inhibited by the addition of anti-human platelet-derived growth factor (PDGF) antibody. However, antibodies against interleukin 1-beta, tumor necrosis factor-alpha and endothelin-1 did not affect the stimulatory effect of CM. Moreover, the modulator contained in CM was stable at 100 degrees C, and pH 2.5 at 22 degrees C for 30 min. When treated with 2 mM mercaptoethanol, this activity was almost completely lost. These findings suggest that GEN promote GMC growth in co-culture systems, without direct contact, by means of a PDGF-like substance.

Animals↗

PubMed1995

Sequence of the canine c-yes proto-oncogene.

Cloning of the canine yes oncogene was attempted from a cDNA library derived from a healthy canine spleen using a human c-yes-1 probe. The nucleotide and amino acid sequences revealed that the canine yes gene contained an open reading frame consisting of 539 amino acids. Its product had a molecular mass of 60,368 Daltons and showed 95.9 per cent and 90.4 per cent homology with human and chick p61c-yes, respectively. Moreover, the product had a myristylation signal, src homology region (SH) 3, SH2, and tyrosine kinase domains showing 98.8 per cent and 96.0 per cent homology with those of human beings and chickens, respectively. These findings indicate that the products of the canine yes gene may have non-receptor-type tyrosine kinase activity on the cell membrane, as is the case in human and chick p61c-yes.

Amino Acid Sequence↗

PubMed1995

In vitro growth inhibition activities of recombinant feline interferon on all lines derived from canine tumours.

To evaluate the anti-tumour effect of recombinant feline interferon (rFeIFN) against canine neoplastic cells, the antiproliferation and anti-colony-forming activities of rFeIFN were investigated in vitro, using four cell lines derived from canine tumours; oral acanthomatous epulis (MCA-B1), mammary benign mixed tumour (MCM-B2), squamous cell carcinoma (CSCC), and malignant melanoma (CMC-1). The rFeIFN had a dose-dependent inhibitory effect on the cell growth and colony formation of all the cell lines, although the degree of inhibition was lower than that in the feline cell lines used as a positive control, and the sensitivity of the cells to rFeIFN differed.

Animals↗

PubMed1995

A cell line (MCA-B1) derived from a canine oral acanthomatous epulis.

A canine oral acanthomatous epulis cell line designated MCA-B1 was established in culture. Immunohistochemically the cells reacted intensely with anti-keratin antibody and mildly with anti-vimentin antibody. An ultrastructural examination of the cells confirmed their epithelial nature. The modal chromosome number was 72 and the cloning efficiency in soft agar culture ranged from 3.4 to 16.1 per cent with a population doubling time of nine hours. MCA-B1 has since been passaged more than 70 times and maintained in culture for more than a year. Most of the characteristics of the original canine tumour cells were retained in the isolated cell line.

Animals↗