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Biomedical subjects

A Takeda

Publications and source records attributed to A Takeda.

At least 253 records · Page 14Linked to original sources

Urinary excretion of epidermal growth factor in children with reflux nephropathy.

PURPOSE: We determined urinary levels of epidermal growth factor in children with reflux nephropathy to evaluate the clinical significance of urinary epidermal growth factor. MATERIALS AND METHODS: We studied 59 boys and 41 girls 3 to 15 years old with reflux nephropathy, and 64 boys and 36 girls 3 to 15 years old who were healthy. Levels of urinary epidermal growth factor were determined by sandwich enzyme immunoassay using spot urine samples. We also determined the levels of serum creatinine, urinary alpha 1-microglobulin and urinary microalbumin. Absolute values of function of the left and right kidneys were assessed by 99mtechnetium dimercapto-succinic acid (DMSA) uptake. RESULTS: Levels of urinary epidermal growth factor gradually decreased with age in healthy children. There were low levels of urinary epidermal growth factor in 20 of the 44 patients (45%) with unilateral low DMSA uptake and 18 of the 19 (95%) with low total DMSA uptake (right and left uptakes). Urinary epidermal growth factor significantly correlated with serum creatinine (R = -0.702, p < 0.0001), urinary alpha 1-microglobulin (R = -0.606, p < 0.0001), urinary microalbumin (R = -0.708, p < 0.0001) and total DMSA uptake (R = 0.744, p < 0.0001). CONCLUSIONS: These results suggest that urinary epidermal growth factor may be a useful clinical tool to monitor functional nephron mass in children with reflux nephropathy.

Adolescent↗

[Variations in mesenchymal cell activity between rheumatic and non-rheumatic valve disease].

Deoxyribonucleic acid (DNA) synthesis of mesenchymal cells in the diseased valve tissue of patients with rheumatic and non-rheumatic valve diseases were compared. Surgically resected mitral valves from eight rheumatic and eight non-rheumatic patients in their 40s were examined immunohistochemically to estimate the activity of the various mesenchymal cells by cell cycle analysis, using monoclonal antibodies to cyclin E, A, B1, p53, and b cl-2 after routine tissue fixation, paraffin embedding and sectioning. Cyclin B1-positive fibrocytes and fibroblasts of the spongiosa and fibrosa were observed in all non-rheumatic cases, whereas some lymphocytes in the perivascular area were cyclin B1-, p53- and b cl-2-positive in rheumatic cases. The distinct qualitative difference in the mesenchymal cells of valve tissue between rheumatic and non-rheumatic etiologies suggests a different mode of valve pathology.

Adult↗

[Effect of injection speed on sensory blockade in spinal anesthesia with 0.5% hyperbaric tetracaine].

We investigation the effect of injection speed on sensory blockade in spinal anesthesia. Forty two female patients, scheduled for total abdominal hysterectomy, were allocated randomly to 3 groups of 14 each according to the injection speed of 0.5% hyperbaric tetracaine: Group F (fast; injection speed > or = 0.2 ml.s-1), Group M (moderate; 0.1 < injection speed < 0.2 ml.s-1) and Group S (slow; injection speed < or = 0.1 ml.s-1). Spinal puncture was performed via the median approach at the L3-4 interspace with the patient in a lateral position. The maximum level of sensory blockade was assessed by means of the pin-prick method in the midline 3, 5, 10, 20, 30, 60 minutes after injection. In Group F, the level of sensory blockade became higher quickly (within 5 min), but anesthetic effects were not so satisfactory. And, in this group, there were more patients with dyspnea than in other groups. We speculate that the turbulence made by fast injection in subarachnoid space caused unsatisfactory effects. In Group S, anesthetic level was becoming higher also 20 or 30 min after injection. The fixation of anesthetics requires about 30 min. In our opinion, anesthetics injected slowly were diluted less by CSF, and the actual baricity of them was higher, and this made the difference within 30 min. In Group M, anesthetic effects and patient's condition were stable. We suppose that this injection speed (0.1-0.2 ml.s-1) is suitable for spinal anesthesia.

Adult↗

[Effects of pimobendan on pulmonary hypertension in patients with chronic pulmonary emphysema].

Pimobendan is a positive inotropic agent that dilates blood vessels and sensitizes the myocardium to calcium. We studied the clinical usefulness of single oral doses of pimobendan (2.5 mg) in 8 patients with pulmonary hypertension caused by chronic pulmonary emphysema. We measured the short-term effects of pimobendan on pulmonary hemodynamics and gas exchange. Pimobendan significantly decreased mean pulmonary artery pressure from 23.4 +/- 3.4 to 18.5 +/- 2.5 mmHg, and total pulmonary resistance from 383 +/- 111 to 281 +/- 81 dyne.sec.cm-5, while oxygen delivery and cardiac output increased significantly (oxygen delivery: from 81.8 +/- 10.2 to 93.5 +/- 16.2 ml O2/min. cardiac output: from 4.98 +/- 0.76 to 5.77 +/- 1.49 l/min, means +/- SD). Systemic vascular resistance was not significantly reduced. The ratio of pulmonary to systemic vascular resistance was reduced, but not significantly. Arterial oxygen tension (PaO2) and arterial carbon dioxide tension (PaCO2) did not change significantly. These results indicate that pimobendan may be useful in the treatment of patients with secondary pulmonary hypertension.

Aged↗

[Arterial infusion chemotherapy in pelvic space for advanced rectal cancer].

Three rectal cancer patients were treated with arterial infusion chemotherapy through the internal iliac artery. Two patients with pelvic recurrences unresectable after APRA were treated with intensive chemotherapy and the other patient with neoadjuvant chemotherapy. In all cases, 5-FU (500 mg/ body/day) was administered continuously for 5 days or 14 days. We attempted three methods for this procedure which were a bilateral catheterization to the internal iliac artery, a single catheterization with an embolization to the other internal iliac artery and a single catheterization without the embolization. As the result of this treatment, in the resected specimen with neoadjuvant case, histological necrosis was found in 50% in the main tumor and the metastatic lymph nodes. One patient with pelvic recurrence showed a partial response in CT imaging, but died one year later of the recurrence around the external iliac artery. The other patient with pelvic recurrence treated with the bilateral catheterization had no efficacy on CT imaging, but his CEA level has decreased at present. It was concluded that arterial infusion chemotherapy was effective for advanced rectal cancer and the pelvic recurrences. However, the efficacy of this treatment is limited to the area to which the drugs are delivered. Thus, it is important that the method and the location of the catheterization are determined adequately for each case.

Antidotes↗

[Evaluation of CTA for arterial infusion chemotherapy for liver metastasis from colorectal cancer].

To compare between the arterial blood supply of metastatic liver tumor and effects of intrahepatic arterial infusion chemotherapy (IHAC), we examined 8 patients with 27 liver metastasis from colorectal cancer. They were treated with ADM/lipiodol/5-FU/LV (19 nodules) or 5-FU/LV (8 nodules). To evaluate the arterial blood supply, CT arteriography (CTA) was performed, which classified tumors into 3 grades. Grade (Gr) 0; almost no enhancement, Gr1: less than one-third of tumor, Gr 2; less than two-thirds; Gr 3 over two-thirds (no case). As a result, 3 of NCs and 3 of PDs were Gr 0, 7 of MRs, 3 of NCs and 2 of PDs were Gr 1, and CR, PR and 7 of MRs were Gr 2. These results suggest that the arterial blood supply is necessary for a better response of IHAC and CTA is effective to forecast the response to IHAC.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical efficacy of post-TUR prophylactic chemotherapy for superficial bladder cancer--the result of co-operative prospective randomized trial].

We have performed a prospective randomized clinical trial of post-operative prophylactic therapy for superficial bladder cancer since October in 1991. The criteria were as follows; age < or = 80 y.o., Ta/T1, TCC G1/G2, without CIS lesion and resectable cancer by TUR. The therapeutic arm was divided into three as follows: arm A intracystic instillation with Epirubicin; arm B: oral administration with 5-FU; arm C: combination of arm A and arm B. The number of registered patients were 20 in arm A, 18 in arm B, and 18 in arm C. The patient characteristics in every group were not significantly different. The prophylactic efficacy of arm A was superior to that in the other two groups.

Administration, Intravesical↗

Assignment of the CD45-AP gene to the centromeric end of mouse chromosome 19 and human chromosome 11q13.1-q13.3.

CD45-AP is a recently identified phosphorylated protein that specifically associates with the leukocyte-specific transmembrane glycoprotein CD45. The gene for CD45-AP, Ptprcap (protein tyrosine phosphatase, receptor type c polypeptide associated protein), was mapped in mouse by typing the progeny of two multilocus crosses using the mouse CD45-AP cDNA as a Southern hybridization probe. The CD45-AP gene mapped to the centromeric region of Chr 19 proximal to the genes Fth, Cd5, and Pcna-rs. The gene for the human CD45-AP homologue, PTPRCAP, was localized to chromosome band 11q13.1-q13.3 by fluorescence in situ hybridization using human genomic CD45-AP DNA as a hybridization probe. The genetic mapping of the Ptprcap/PTPRCAP genes extends the previously defined synteny conservation of various genes that have been assigned to these regions of the mouse and the human chromosomes.

Animals↗

The effect of long-term post-ischemic bifemelane hydrochloride treatment on cholinergic systems in the gerbil hippocampus.

Bifemelane hydrochloride (BF) is a modulator of various neurotransmitter systems. The effect of BF on the cholinergic system was studied in the gerbil hippocampus at 100 days after ischemic damage. Marked enhancement of AChE staining was noticed in the CA1 of saline-treated animals at 100 days after ischemia, while the post-ischemic enhancement of AChE staining intensity was milder in BF-treated animals. Muscarinic receptor density was markedly decreased in the CA1 subfield after ischemia. Interestingly, BF-treated animals showed higher muscarinic receptor binding in many brain areas, particularly in the dentate gyrus. These results indicate that BF modulates cholinergic neuronal plasticity in the ischemic hippocampus after long-term survival.

Acetylcholinesterase↗

Regional difference in induction of heme oxygenase-1 protein following rat transient forebrain ischemia.

Heme oxygenase (HO) is a rate-limiting enzyme in heme catabolism, the end products of which include iron, carbon monoxide and bilirubin. We investigated the changes in expression of an inducible form, heme oxygenase-1 (HO-1), and a constitutive form, HO-2, in rat brain following 20 min of forebrain ischemia, using specific antisera for HO-1 and HO-2. HO-1 protein was remarkably induced in brain following ischemia, while the level of HO-2 protein was not noticeably affected. The level of HO-1 protein expression was maximal at 12 h, which is in good agreement with the time course of the HO-1 mRNA induction. In the cortical mantle, most of the cells expressing increased HO-1 protein were identified as pyramidal neurons and astrocytes by their shapes and locations. In hippocampal CA-2 and CA-3 subfields, prominent induction was observed in astrocytes rather than in neuronal cells. By contrast, the HO-1 protein was not detected in the CA1 subfield following the insult, although the increased level of transcripts was evident in neurons and glial cells. These results suggest that not only in neuronal cells but also in astrocytes within the CA1 subfield, there may be an impairment of protein metabolism, preceding the delayed CA1 pyramidal cell losses.

Animals↗

p53 gene alterations and p53 protein in oral epithelial dysplasia and squamous cell carcinoma.

To examine the expression of p53 protein and gene alterations in oral epithelial lesions including epithelial dysplasias and primary squamous cell carcinomas, immunohistochemical and temperature gradient gel electrophoresis (TGGE) methods were applied to formalin-fixed and paraffin-embedded tissues. Morphologically normal mucosal epithelium stained negatively for p53 protein. Three out of 11 (27.3 per cent) epithelial dysplasias and 19 out of 57 (33.3 per cent) primary squamous cell carcinomas stained positively for p53 protein. Although more than half of the cases were positive for p53 protein in stage I, the positive cancer cases were found at other stages with variable frequency. Immunoreactive products were localized in the nucleus, especially in the basal and suprabasal layers. The analysis by TGGE revealed gene alterations in exons 5-8 in 3 out of 3 epithelial dysplasias and 17 out of 19 (89.5 per cent) primary squamous cell carcinomas which were immunohistochemically positive for p53 protein. These results suggest that p53 gene mutation may be involved in carcinogenesis in the oral squamous epithelium even in the early stage of the dysplasia-carcinoma sequence.

Adult↗

Upregulation of Bcl-2 protein in the myasthenic thymus.

We examined the expression of Fas antigen and Bcl-2 protein in thymic tissue surgically resected from 10 patients with myasthenia gravis, using immunocytochemical techniques. Histologically, thymic tissues from 7 myasthenia gravis patients showed hyperplasia, while 3 other patients had thymomas. In hyperplastic thymic tissue, immunoreactivity for Fas antigen was observed mainly in the network of medullary epithelial cells. In contrast, expression of Fas antigen was rare in the cortex. Fas antigen was also detected to some degree in thymoma tissue from 3 patients. Bcl-2 protein was highly expressed in the medullary thymocytes in the hyperplastic thymic tissue, whereas its staining was quite low in myasthenia gravis thymomas. The number of Bcl-2-positive thymocytes in the medulla was significantly greater in the hyperplastic myasthenia gravis thymic tissue than in the control thymic tissue. These findings suggest that Bcl-2 protein may be upregulated in the myasthenia gravis thymus and that this phenomenon may be related to impaired apoptotic cell death of autoreactive thymocytes in myasthenia gravis.

Adult↗

Selective accumulation of anti-histone antibodies in glomeruli of lupus-prone lpr mice.

Immunoglobulins were eluted from glomeruli of 50 lupus-prone, lpr mice and their physicochemical properties and specificity were compared with those in sera pooled from the same mice. Although immunoglobulins in glomeruli had higher isoelectric points than those in sera, there were no appreciable differences in the relative contents of neutral and acidic immunoglobulins between them. The proportion of IgG3 subclass was slightly higher in glomerular than serum immunoglobulins. Both anti-single-stranded and anti double-stranded DNA antibodies were twofold higher in glomerular than serum immunoglobulins, while anti-Sm antibodies were not recovered in glomerular eluate despite their high activity in serum. Antibodies in glomerular eluate reacted most strongly with histones, especially with core histones, while those in sera bound preferentially with histone H1, Sm-B, -B', and -D antigens. Since histones are very basic, they would have a higher affinity for negatively charged glomerular constituents, leading to an in situ formation of immune complexes involving fixed histones and their binding with antibodies for the induction of nephritides. Otherwise, such immune complexes themselves might retain positive charges sufficient for an affinity with the glomerular basement membrane. These results indicate that histone-anti-histone antibody system may play a role in the perpetuation of murine lupus nephritis.

Animals↗

Risk factors for relapse in childhood nephrotic syndrome.

We investigated the risk factors for relapse in 48 children with steroid-sensitive nephrotic syndrome using univariate and multivariate proportional hazard analysis. All patients were treated with the same corticosteroid regimen. A low serum level of total protein and young age at onset increased the relapse rate. Recurrence risk was not associated with the patient's sex, the percentage body weight gain, blood urea nitrogen level, serum level of creatinine, the hematocrit, or the administration of human albumin. We conclude that young age and a low serum level of total protein at onset were independent risk factors for relapse of childhood nephrotic syndrome.

Adolescent↗

Purification and characterization of bleomycin hydrolase, which represents a new family of cysteine proteases, from rat skin.

Bleomycin (BLM) hydrolase, which hydrolyzes the carboxyamide bond in the beta-amino-alanine moiety, was purified from newborn rat skin. The enzyme was purified 2,500-fold over the crude extract to apparent homogeneity in five steps in the presence of 2-mercaptoethanol: 45-55% ammonium sulfate fractionation, followed by chromatographies on Sephacryl S-200, DEAE-cellulofine, Phe-Superose, and Mono Q ion-exchange. The native enzyme had a molecular mass of 280 kDa according to gel filtration. The subunit molecular mass was estimated as 48 kDa by SDS-PAGE, indicating that the enzyme was comprised of six identical subunits. The amino acid sequence of its NH2-terminus was determined to be acetyl-Met-Asn-Asn-Ala-Gly-Leu-Asn-Ser-Glu-Lys-, which was not found in the amino acid sequence database. The optimum pH of the enzyme was 7.5 with pepleomycin (PLM). The Km and Vmax values were 2.1 mM and 6.8 mu mol center dot mg-1 center dot h-1 for PLM, and 1.8 mM and 7.2 mu mol center dot mg-1 center dot h-1 for BLM-A2, respectively. The enzyme activity was inhibited by iodoacetic acid, N-ethylmaleinimide (NEM), and p-chloromercuribenzoic acid (pCMB) as well as divalent cations such as Cu2+, Cd2+, Hg2+, and Zn2+. It was effectively inhibited by a cysteine protease inhibitor E-64. However, cystatins A and C did not inhibit the activity. BLM hydrolase exhibited broad aminopeptidase substrate specificity towards aminoacyl-beta-naphthylamides such as basic, neutral, and hydrophobic amino acid residues, as well as acidic residues. These results indicated that BLM hydrolase represents a new family of cysteine proteases. Western blotting and immunohistochemical analyses showed that BLM hydrolase is ubiquitous in various rat tissues but at low levels in lung and adult skin tissues, suggesting that this enzyme plays an important role in the metabolism of antibiotics.

Amino Acid Sequence↗

Cloning and analysis of cDNA encoding rat bleomycin hydrolase, a DNA-binding cysteine protease.

We isolated and characterized almost the entire cDNA encoding BLM hydrolase from rat spleen cDNA libraries. The cDNA encoded a polypeptide composed of 454 amino acids, that had a slightly larger molecular mass than that was previously estimated by SDS-PAGE for purified BLM hydrolase subunit. Amino acid sequence alignments showed that rat BLM hydrolase is homologous to that of rabbit (94% identity of partial amino acid sequence), yeast cysteine protease (39% identity), and the pepC gene products of three bacteria (34-40% identity). In addition, it contained the three regions that are conserved in other cysteine proteases and thought to constitute the catalytic center. These results indicated that rat BLM hydrolase is a member of the papain superfamily of cysteine proteases. Sequencing revealed several putative sites phosphorylated by different types of protein kinases, but no signal sequence, transmembrane domain, N-linked glycosylation site or DNA-binding motif. The yeast homolog is a DNA-binding cysteine protease [Xu et al. (1994) J. Biol. Chem, 269, 21177-21183]. We demonstrated that rat BLM hydrolase also binds the single-stranded form of the Ga14 DNA-binding site oligonucleotide with high affinity compared with that of the double-stranded form. Northern blots revealed that the level of BLM hydrolase mRNA expression was very low in the rat skin, lung, and skeletal muscle. Furthermore, BLM hydrolase mRNA was ubiquitously expressed in the human cell lines, HeLa, SKG-IIIa, FL, KB, HEp-2, U373 GM, P3HR-1, Raji, THP-1, Jurkat, and Molt-4. These results suggested that BLM hydrolase plays important physiological roles, including the metabolism of antibiotics.

Amino Acid Sequence↗