Search PubMed⌕ Search

Biomedical subjects

A Takeda

Publications and source records attributed to A Takeda.

At least 343 records · Page 19Linked to original sources

Three-dimensional distribution of myocardial fibrosis in the new J-2-N cardiomyopathic hamster: comparison with electrocardiographic findings.

Using the new J-2-N strain of cardiomyopathic hamster obtained by cross-breeding Bio 14.6 and Golden hamsters, we investigated the three-dimensional distribution of ventricular myocardial fibrosis and compared it with electrocardiographic (ECG) changes. Twelve-lead ECG recordings were made by our own method. The hearts were cut into serial sections and subjected to light microscopic examination. The distribution, density, and volume of myocardial interstitial fibrosis and replacement fibrosis due to myocardial degeneration (F%) were visualized three-dimensionally using the TRI system (TRI; Three-Dimensional Reconstruction Image; Ratoc System Engineering, Tokyo, Japan). Thirty-two J-2-N hamsters were divided into two groups; one group comprised 17 animals with normal hearts and normal ECG findings similar to those of Golden hamsters, and the other group of 15 hamsters had dilated hearts and abnormal ECG findings. In the normal hearts, the F% values for the right ventricle, left ventricle, and ventricular septum were 6.4 +/- 0.94, 6.5 +/- 0.95, and 6.5 +/- 0.98 (mean +/- SD), respectively. The dilated hearts showed marked fibrosis, which was distributed mainly in the middle layer of the left ventricle and the ventricular septum. The corresponding F% values for the hamsters with cardiac enlargement were 19 +/- 2.6, 19 +/- 1.8, and 22 +/- 3.2 (mean +/- SD), respectively. Replacement of myocytes by fibrosis seemed to correspond to abnormal Q waves in the anterior chest leads and left axis deviation of the QRS complex.

Animals↗

Coordinated expression of messenger RNAs for nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the rat hippocampus following transient forebrain ischemia.

Changes in nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 messenger RNA expression in the rat hippocampus following 20 min of transient forebrain ischemia were evaluated using Northern blot analysis and in situ hybridization histochemistry. Twelve hours after the insult, the level of nerve growth factor messenger RNA increased markedly in the granular cell layer of the dentate gyrus and by day 2 returned to control levels. The level of brain-derived neurotrophic factor messenger RNA showed a persistent and moderate increase. The highest expression of brain-derived neurotrophic factor messenger RNA was seen in the dentate granule cells on day 2 after the insult, and then the expression returned to the control levels. At 2 days post-ischemia, contents of messenger RNAs for nerve growth factor and brain-derived neurotrophic factor were reduced in the CA1 region, which may represent delayed loss of vulnerable CA1 pyramidal neurons. In contrast to brain-derived neurotrophic factor and nerve growth factor messenger RNA expression, the level of neurotrophin-3 messenger RNA declined in the CA1, the CA2 and the dentate granular layer immediately after ischemic insult. In the CA1 region, the reduced expression persisted for at least seven days, but in the dentate gyrus, neurotrophin-3 messenger RNA expression returned to the control levels after two days of post-ischemic recovery. These results suggest that nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 genes are differentially regulated and that each of their gene products may play different roles in the central nervous system under pathophysiological conditions.

Animals↗

Tumor imaging with technetium-99m-DTPA encapsulated in RES-avoiding liposomes.

For passive targeting of liposomes to tumor tissues, we earlier developed reticuloendothelial system (RES)-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). In the present study, we encapsulated technetium-99m (99mTc)-diethylenetriaminepentaacetic acid (DTPA) in PGlcUA-liposomes (dipalmitoylphosphatidylcholine:cholesterol:PGlcUA = 40:40:20 as a molar ratio) and studied the biodistribution of the liposomes in tumor-bearing mice. 99mTc-DTPA encapsulated in liposomes effectively accumulated in tumor tissues after intravenous administration. Corresponding to these results, tumor was strongly imaged by a gamma-camera when 99mTc-DTPA-encapsulated PGlcUA-liposomes were used.

1,2-Dipalmitoylphosphatidylcholine↗

Liver distribution of 99mTc-DL-homocysteine in experimental hepatitis rats.

Liver accumulation of 99mTc-DL-homocysteine (99mTc-Hcy), which had been found to accumulate in several experimental tumors, was studied using experimental hepatitis models of rats. The distribution of this compound in liver of rats treated with CCl4 (25-100 microL/100 g body weight) was more than five times higher than that of non-treated rats, corresponding to the accumulation of Evans Blue, a marker dye for capillary permeability. Furthermore, in vitro experiments indicated that the liver accumulation of 99mTc-Hcy was due to some changes in the plasma membranes caused by CCl4 administration. These results indicate that lesional accumulation of 99mTc-Hcy is due to, at least in part, an enlarged capillary permeability similar to the case of malignant tissues reported previously.

Animals↗

Direct detection of infectious human immunodeficiency virus type 1 (HIV-1) immune complexes in the sera of HIV-1-infected persons.

The sera of human immunodeficiency virus type 1 (HIV-1)-infected subjects were examined for the presence of infectious HIV-1-antibody complexes by their ability to infect Fc gamma receptor (Fc gamma R)-bearing cells. Infection of Fc gamma R-bearing cells by a serum in which half of the p24 antigen was present in a form of immune complexes was inhibited by aggregated human immunoglobulin. Then in studies on 22 sera, 9 sera produced p24 antigen during 14 days of culture in U937 cells. HIV-1 p24 production was inhibited or delayed by the pretreatment of cells with aggregated human immunoglobulin in 6 of the 9 sera that were infectious. These results may reflect interactions between virus-antibody complexes and Fc gamma R-bearing cells in vivo because serum itself was used as the source of virus and virus-antibody complexes. The results indicate that infectious HIV-1 immune complexes are present in the circulation of HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗

A cultured skin substitute composed of fibroblasts and keratinocytes with a collagen matrix: preliminary results of clinical trials.

The cultured skin substitute was created through successive cultivation of fibroblasts and keratinocytes that were combined within a collagen matrix. This collagen matrix was composed of a collagen spongy sheet and a collagen gel. The collagen spongy sheet was designed to produce a honeycomb structure having many holes in which all holes through the sheet were filled with collagen gel. This specific structure thereby allows for the nourishment of the cultured keratinocytes on the surface of the matrix when placed on the graft bed. In this study, autologous cultured skin substitute was applied to a 51-year-old man who had sustained a burn injury. Three sheets of the cultured skin substitute (6 x 9.5 cm) were grafted onto the full-thickness excised wound in the right anterior chest wall. One week after grafting most of the matrix disappeared and stratified keratinocytes were seen to have firmly attached to the underlying tissue. Five weeks after grafting a cornified epidermal layer was seen. Ten months after grafting a mature epidermis and a well-differentiated papillary and reticular dermis replacement were observed. The physical properties and color of this grafted area resemble those of normal skin. In the second test case, autologous cultured skin substitute was applied to a 30-year-old man with a scar remaining after tattoo removal. Eight sheets of the cultured skin substitute (10 x 18 cm) were applied on an excised wound (thickness, 0.02-0.025 in.) of both the fore- and upper arms. The histological appearance of a biopsied skin specimen from the grafted area at 3 months after grafting showed a mature epidermis and a well-differentiated reticular dermis replacement. The regenerated skin at 14 months after grafting showed an excellent result.

Adult↗

Role of endothelium in biphasic hypoxic response of the isolated pulmonary artery in the rat.

We investigated the roles of the endothelium in the hypoxic responses of the isolated main pulmonary artery (PA) in the rat. Hypoxia was induced by gassing an organ chamber with 95% N2 + 5% CO2 (PO2 = 34.6 +/- 3.1 Torr) instead of 16% O2 + 5% CO2 + balance N2 (PO2 = 92.8 +/- 3.0 Torr). Vascular rings were precontracted with 2 x 10(-8) M phenylephrine. A transient hypoxic contraction and a subsequent relaxation were observed in the endothelium-intact rings. The hypoxic contraction was reduced in the endothelium-denuded rings. In contrast, there were no significant differences between the hypoxic relaxation in the endothelium-intact and endothelium-denuded rings. Inhibitors of endothelium-derived relaxing factor (EDRF) activity, 2 x 10(-6) M NG-monomethyl-L-arginine (L-NMMA) and 10(-6) M methylene blue, produced 53% and 66% reductions in hypoxic contraction, respectively, Furthermore, the amount of cyclic GMP in the endothelium-intact PA rings which had been precontracted with phenylephrine decreased from 2.10 +/- 0.45 pmol/mg protein during normoxia to 0.90 +/- 0.18 pmol/mg protein during hypoxia. Indomethacin and OKY-046 did not influence hypoxic contraction or relaxation. These results suggest that hypoxic contraction of the isolated pulmonary artery in the rat is partially induced by inhibition of the release of EDRF.

Animals↗

Adult Still's disease with Sjögren's syndrome successfully treated with intravenous pulse methylprednisolone and oral cyclophosphamide.

A patient with adult Still's disease and Sjögren's syndrome failed to respond to conventional doses of corticosteroids. Therefore intravenous pulse methylprednisolone combined with oral cyclophosphamide was given which subsequently resolved the flare of rashes, fevers, and arthritis. This combination therapy may be a useful therapy to consider in patients with adult Still's disease who are resistant to conventional treatment and may allow a reduction in daily corticosteroid requirement.

Administration, Oral↗

Expression of ras-P21 and ras gene alteration in pleomorphic adenomas.

The expression of ras-P21 protein and gene alteration of the K-ras gene were examined in 12 cases of pleomorphic adenoma of the salivary gland. The tumor cells in all 12 cases were strongly stained for ras-P21 protein by the indirect immunoperoxidase method, suggesting the enhanced expression of ras-P21 protein in pleomorphic adenomas. Analysis of the PCR products for the K-ras gene by temperature-gradient gel electrophoresis (TGGE) revealed that gene alterations such as point mutations occurred in 4 out of 12 pleomorphic adenoma tissues examined.

Adenoma, Pleomorphic↗

The effect of enalapril on proteinuria in patients with chronic glomerulonephritis and renal insufficiency.

We evaluated the effect of enalapril on proteinuria in 20 patients with chronic glomerulonephritis (CGN) and renal insufficiency. Patients were accepted into the study according to the following criteria: 1) a serum creatinine (s-Cr) level over 1.5 mg/dl or a creatinine clearance (Ccr) under 70 ml/min; and 2) urinary protein (UP) over 1.0 g/day, expect for the cases with uncontrollable hypertension. We measured total protein (TP), albumin, s-Cr, Ccr, UP, and Ht during the elanapril therapy. After enalapril therapy, UP slowly decreased, and TP and albumin levels increased. The levels of s-Cr and Ccr did not vary. None of the patients required discontinuation of enalapril therapy caused by side effects, such as anemia or hyperkalemia. In conclusion, enalapril has the effect of decreasing in proteinuria and increasing TP and albumin in patients with CGN and renal insufficiency irrespective of the original diseases.

Adolescent↗

[Giant cell arteritis and polymyalgia rheumatica presenting as subclavian artery obstruction].

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common diseases in the elderly. The arteritis usually affects medium sized vessels, but large vessel involvement can also occur leading to arm claudication, bruits, loss of pulses and pallor of the upper extremities. The differential diagnosis of large vessel arteritis includes atherosclerosis and Takayasu's disease. Atherosclerosis, which affects patients of similar age to GCA is usually confined to the lower limbs and can be differentiated on the basis of the clinical setting and investigations such as the ESR, arteriography and temporal artery biopsy. Takayasu's arteritis' although histologically and arteriographically indistinguishable from GCA, is predominantly a disease of young women. A patient is described who presented with upper limb ischemia. A clinical examination revealed absence of right radial pulses and presence of murmurs at level of the carotids. The blood pressure was unrecordable in the upper right limb. The ESR was 102 mm/hr and the C-reactive protein was 11.66 mg/dl. A selective arteriography of the aortic arch and its branches revealed a right subclavian artery obstruction with good collateral circulation and a left subclavian artery stenosis. The biopsy of left temporal artery showed a typical GCA in acute stage. Treatment with prednisolone 30 mg/day was started and four weeks later, the ESR had fallen to normal. In addition this case confirms that PMR implies a systemic arteritis.

Arterial Occlusive Diseases↗

[Analysis of MDR1 (multidrug resistance) gene expression by RT-PCR].

Multidrug resistance to anticancer drugs proved to be related to the MDR1 gene which encodes the P-glycoprotein, an energy-dependent drug-efflux pump for lipophilic drugs. We investigated the expression of the MDR1 gene in clinical samples by RT-PCR. The subjects were all resected cases of 14 colorectal cancers, five gastric cancers, two esophageal cancers, two gallbladder cancers and 20 lung cancers. Adrenal gland was used as a positive control. Total RNA was extracted from a fresh tissue sample. The cDNA was synthesized from 1 microgram of total RNA using reverse transcriptase. With the above cDNA as the template, amplification of the 157-bp fragment of the MDR1 gene was performed using PCR. The PCR product was polyacrylamide gel-electrophoresed and ethidium bromide-stained. In addition, a dot blot analysis was performed to quantify the amount of PCR product. Since PCR was performed simultaneously under the same conditions, the PCR product was quantified at four stages, from (3+) to (-), to indicate the degree of expression of MDR1 mRNA. Adrenal gland showed (3+)-(2+) and colorectal cancer exhibited mostly (2+)-(1+). Both cancerous and non-cancerous areas evidenced a similar degree of expression in the cases of colorectal cancer. The MDR1 gene was expressed at low levels in other digestive tract cancers and in lung cancer. The levels of MDR1 expression revealed no correlation to either histological type or clinical stage. The present method may contribute to designing anti-cancer protocols.

Antineoplastic Agents↗