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Biomedical subjects

S Adachi

Publications and source records attributed to S Adachi.

At least 145 records · Page 8Linked to original sources
PubMed1997

Three distinctive steps in Peyer's patch formation of murine embryo.

Investigation of the process of Peyer's patch (PP) formation has been hampered by difficulties in identifying its initial step in the embryo. In this study, we overcame this problem by means of whole-mount immunohistochemistry using mAb against the molecules which were expressed in the cells accumulated at the site of PP development. This method was sensitive enough to distinguish a minute cell cluster in the developing gastrointestinal tract. We analyzed the time course of the expression of various surface markers and found that PP formation proceeds through three successive steps. The first is the appearance of a VCAM-1+ cell cluster at 15.5 days postcoitus (d.p.c.). Histological examination of the VCAM-1+ clusters suggested that VCAM-1+ cells represent a stromal component. The second step is characterized by the accumulation of round cells expressing la, IL-7R or CD4 at 17.5 d.p.c. Lymphocytes expressing CD3 or B220 were detected only in the final step which started at 18.5 d.p.c. Using any of these markers, the aggregation was initially detected on the upper jejunum and it extended to the colon as the number of clusters increased. At the neonatal stage, the number reached up to eight or nine, irrespective of the antibodies used for the detection. In the aly/aly mutant mouse, where no lymph nodes or PP are found in the adult, none of these three steps was detected. On the other hand, in the SCID mouse that is defective in the formation of mature lymphocytes, the first and second step proceeded, whereas the third step was undetectable. These findings suggest that the progression of each step is indeed regulated by different mechanisms.

Animals↗
PubMed1997

Combination chemotherapy using intravenous nedaplatin (254-S) and intraarterial cisplatin (CDDP) with transcatheter arterial embolization (TAE) for a patient with uterine cervical cancer: a case report.

A 45-year-old Japanese woman with a bulky (75 x 40 mm) stage 2a uterine cervical cancer was treated with 87 mg (50 mg/m2) of nedaplatin (254-S) intravenously and 120 mg (70 mg/m2) of cisplatin (CDDP) intraarterially with transcatheter arterial embolization (TAE). She received three courses of this combination chemotherapy and showed a complete response, as confirmed by magnetic resonance imaging. A radical hysterectomy was performed and the pathological findings revealed the absence of carcinoma cells. This type of combination chemotherapy seems to be effective for the treatment of locally advanced uterine cervical cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Spontaneous healing of pancreatic abscess after fistulization to the duodenal bulb.

A 70-year-old man was admitted to the hospital because of sudden, upper abdominal and back pain. Laboratory and image data indicated acute pancreatitis. Shortly after the admission, pancreatic and liver abscess with bacteremia developed. Antibiotic therapy seemed effective. A month later, spontaneous fistulization of the pancreatic abscess to the duodenal bulb was found by gastroduodenal fiberscopy. Injection of contrast medium into the duodenal orifice showed that the fistula was draining the abscess and that no other fistula formed from the abscess. Endoscopic retrograde cholangiopancreatogram indicated no fistula formation to the pancreatic duct. The pancreatic abscess became smaller and was not visible using computerized tomography and ultrasonography 3 months later and thereafter. Closure of the duodenal orifice was ascertained by the endoscopy. It is suggested that retrograde infection from the fistula was prevented by the single fistulization to the acidic duodenal bulb, which is not supposed to allow most bacterial growth. Pancreatic abscess usually necessitates operative treatment, even with fistulization to the alimentary tract. It seems likely that the single, small fistulization to the bulb, in addition to the lack of underlying disease and medical and nutritional support, facilitated the spontaneous healing process.

Abscess↗
PubMed1997

Biphasic regulation of the preproendothelin-1 gene by c-myc.

Endothelin-1 (ET-1), a potent vasoconstrictive/mitogenic peptide originally isolated from vascular endothelium, stimulates the expression of immediate early response genes such as c-myc. The c-myc protooncogene participates in regulating the cascade of events that follow mitogenic stimulation of quiescent cells. Using a panel of isogenic fibroblast cell lines with differential c-myc expression levels (obtained by disrupting one c-myc gene copy with targeted homologous recombination and subsequently stably transfecting the heterozygous cells with an exogenous c-myc transgene), we demonstrate that c-Myc protein regulates ET-1 gene transcription in a biphasic fashion: as an activator at low concentrations and as a repressor at high concentrations. Using rat endothelial cells treated with antisense c-myc oligodeoxynucleotides, we also show that c-myc regulates ET-1 synthesis and secretion in a biphasic manner. The present report, therefore, demonstrates the existence of a signal transduction pathway that regulates the synthesis and secretion of ET-1 via the immediate early transcription factor, c-Myc.

Animals↗
PubMed1997

Effects of medium-chain fatty acids and their acylglycerols on the transport of penicillin V across Caco-2 cell monolayers.

The transport-enhancing effects of medium-chain fatty acids (caproic, caprylic, and capric acids) and their acylglycerols (mono-, di-, and triacylglycerols) were investigated by using Caco-2 cell monolayers as a model of the human intestinal epithelium. Penicillin V was used as a model for a hydrophilic bioactive compound. Among the fatty acids and acylglycerols tested, 1,2-dicaproin, monocaprin, monocaprylin, and capric acid sodium salt effectively enhanced the transport rate, whereas other substances enhanced the rate only slightly or not at all. With each of these four substances, the rate of enhancement was proportional to the concentration at low concentrations, but leveled off at high concentrations. The transport-enhancing effects were well correlated with the reduction in surface tension and with a physico-chemical parameter, denoted by the surface energy-lowering coefficient, characterizing the surface activity of a substance.

Caco-2 Cells↗
PubMed1997

Porphyria cutanea tarda with constrictive pericarditis in a family.

Two cases of familial porphyria cutanea tarda (PCT) with constrictive pericarditis are described. A 50-year-old woman and her 48-year-old younger brother were admitted because of right ventricular heart failure. Constrictive pericarditis was diagnosed by RV pressure waveform and echocardiogram. The patients were diagnosed as PCT based on clinical symptoms, histologic findings and elevated urinary excretion levels of uroporphyrin. Even to this day, over 40% of the etiology of constrictive pericarditis remains unknown. There is a possibility of overlooking porphyria cutanea tarda in constrictive pericarditis patients. This report describes the first documented cases of familial PCT with constrictive pericarditis.

Coproporphyrins↗
PubMed1997

Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination.

Rat fibroblast cell lines with targeted disruptions of both c-myc gene copies were constructed. Although c-myc null cells are viable, their growth is significantly impaired. The absence of detectable N-myc or L-myc expression indicates that Myc function is not absolutely essential for cell viability. The c-myc null phenotype is stable and can be reverted by introduction of a c-myc transgene. Exponentially growing c-myc null cells have the same cell size, rRNA, and total protein content as their c-myc +/+ parents, but the rates of RNA and protein accumulation as well as protein degradation are reduced. Both the G1 and G2 phases of the cell cycle are significantly lengthened, whereas the duration of S phase is unaffected. This is the first direct demonstration of a requirement for c-myc in G2. The G0-->S transition is synchronous, but S-phase entry is significantly delayed. The c-myc null cell lines reported here are a new experimental system in which to investigate the importance of putative c-Myc target genes and to identify novel downstream genes involved in cell cycle progression and apoptosis.

Animals↗
PubMed1997

[The role of CT and MR imaging in the diagnosis of lung cancer].

CT and MR imaging can play an important role in the diagnosis of lung cancer. Evaluation of a solitary pulmonary nodule is usually carried out using CT. High-resolution CT is useful in the morphologic diagnosis of a solitary pulmonary nodule. The enhancement characteristics of a pulmonary nodule in contrast-enhancement CT can be a method of distinguishing benign and malignant nodules. MR imaging is superior to CT in contrast resolution and multidirectional imaging capability. Contrast-enhancement MR imaging can describe the enhancement characteristics of the pulmonary lesion better than contrast-enhancement CT. The extent of chest wall and mediastinal invasion of lung cancer can be better shown using MR imaging than CT.

Adenocarcinoma↗
PubMed1997

Calcitonin gene-related peptide (CGRP) and hypertrophy of cardiomyocytes.

We studied whether calcitonin gene-related peptide (CGRP), a neuropeptide secreted from the sensory nervous supply to the myocardium, induces hypertrophy of cardiomyocytes in culture. CGRP increased the cell surface area of neonatal rat cardiomyocytes; the surface area of the cells was almost doubled by treatment with CGRP for 48 h. Furthermore, CGRP up-regulated mRNA expression for skeletal alpha-actin and atrial natriuretic peptides, which are genetic markers for cardiac hypertrophy. These results indicate that CGRP is a potent hypertrophic factor for cardiomyocytes.

Animals↗
PubMed1996

Photolysis of the carbon monoxide complex of myoglobin: nanosecond time-resolved crystallography.

The biological activity of macromolecules is accompanied by rapid structural changes. The photosensitivity of the carbon monoxide complex of myoglobin was used at the European Synchrotron Radiation Facility to obtain pulsed, Laue x-ray diffraction data with nanosecond time resolution during the process of heme and protein relaxation after carbon monoxide photodissociation and during rebinding. These time-resolved experiments reveal the structures of myoglobin photoproducts, provide a structural foundation to spectroscopic results and molecular dynamics calculations, and demonstrate that time-resolved macromolecular crystallography can elucidate the structural bases of biochemical mechanisms on the nanosecond time scale.

Carbon Monoxide↗
PubMed1996

Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group.

BACKGROUND: In patients with hepatocellular carcinoma (hepatoma), the rate of recurrent and second primary hepatomas is high despite surgical resection and percutaneous ethanol-injection therapy. We developed an acyclic retinoid, polyprenoic acid, that inhibits hepatocarcinogenesis in the laboratory and induces differentiation and apoptosis in cell lines derived from human hepatoma. In a randomized, controlled study, we tested whether the compound reduced the incidence of recurrent and second primary hepatomas after curative treatment. METHODS: We prospectively studied 89 patients who were free of disease after surgical resection of a primary hepatoma or the percutaneous injection of ethanol. We randomly assigned the patients to receive either polyprenoic acid (600 mg daily) or placebo for 12 months. We studied the remnant liver by ultrasonography every three months after randomization. The primary end point of the study was the appearance of a histologically confirmed recurrent or new hepatoma. RESULTS: Treatment with polyprenoic acid significantly reduced the incidence of recurrent or new hepatomas. After a median follow-up of 38 months, 12 patients in the polyprenoic acid group (27 percent) had recurrent or new hepatomas as compared with 22 patients in the placebo group (49 percent, P = 0.04). The most striking difference was in the groups that had second primary hepatomas--7 in the group receiving polyprenoic acid as compared with 20 in the placebo group (P = 0.04 by the log-rank test). Cox proportional-hazards analysis demonstrated that as an independent factor, polyprenoic acid reduced the occurrence of second primary hepatomas (adjusted relative risk, 0.31; 95 percent confidence interval, 0.12 to 0.78). CONCLUSIONS: Oral polyprenoic acid prevents second primary hepatomas after surgical resection of the original tumor or the percutaneous injection of ethanol.

Aged↗
PubMed1996

Molecular cloning and characterization of Japanese eel estrogen receptor cDNA.

A cDNA encoding the Japanese eel, Anguilla japonica, estrogen receptor (ER) was isolated and sequenced. This cDNA contains a complete open reading frame encoding 573 amino acid residues, and the molecular weight of this protein is calculated to be 63417. The amino acid sequence of the eel ER shows high homology of the DNA binding (80%) and ligand binding (55%) domains with those of other species. However, the other domains show greatly reduced homology (10-20%). When the cDNA was ligated to the pSVL vector and transfected into COS7 cells, a protein was produced that had high affinity for estradiol-17 beta (E2) and specifically bound estrogens. Northern analysis showed that three ER mRNAs with lengths of 5.6, 3.8 and 1.2 kb were expressed in eel liver. Their expression was E2 inducible, with the 5.6 kb mRNA being strongly dependent on E2 stimulation.

Amino Acid Sequence↗
PubMed1996

Heparin and heparan sulfate block angiotensin II-induced hypertrophy in cultured neonatal rat cardiomyocytes. A possible role of intrinsic heparin-like molecules in regulation of cardiomyocyte hypertrophy.

BACKGROUND: Heparan sulfate, one of the primary components of extracellular matrix, is a potent antigrowth factor in certain types of cells. To elucidate a possible role of endogenous heparin-like molecules in regulating cardiomyocyte hypertrophy, we investigated the effects of heparin and heparan sulfate on angiotensin (Ang) II-induced hypertrophy in cultured neonatal rat cardiomyocytes. METHODS AND RESULTS: Competitive [3H]heparin binding assay showed that cardiomyocytes had specific binding sites for heparin. In situ [3H]heparin binding assay demonstrated that heparin, which rapidly bound to the cardiomyocyte surface, was subsequently accumulated around the nuclei, suggesting that heparin might work in the nucleus. Cotreatment with heparin (20 micrograms/mL) completely inhibited increased cell surface area by Ang II (10(-6) mol/L). Increased [3H]leucine incorporation by Ang II was reduced by heparin dose-dependently. The inhibitory effect of heparin on Ang II-induced cardiomyocyte hypertrophy also was confirmed by Northern blot analysis: heparin dose-dependently inhibited skeletal alpha-actin and atrial natriuretic peptide gene expression, genetic markers for cardiomyocyte hypertrophy. Heparan sulfate showed similar inhibitory effects on cell surface area, [3H]leucine incorporation, and skeletal alpha-actin gene expression. Treatment with heparinase I or III, which specifically digests the disaccharide chains of endogenous heparin-like molecules, upregulated protein synthesis and skeletal alpha-actin and atrial natriuretic peptide gene expression in cardiomyocytes. CONCLUSIONS: Our findings in this study strongly suggest that heparin and heparan sulfate are potent inhibitors of cardiomyocyte hypertrophy and that endogenous heparin-like substances negatively regulate cardiomyocyte hypertrophy.

Angiotensin II↗
PubMed1996

Endothelin-3 induces hypertrophy of cardiomyocytes by the endogenous endothelin-1-mediated mechanism.

We have recently reported that endothelin-1 (ET-1) mediates angiotensin II-induced hypertrophy of cardiomyocytes as an autocrine/paracrine factor. In the present study, we examined whether endothelin-3 (ET-3) induces hypertrophy of cultured neonatal rat cardiomyocytes and whether endogenous ET-1 mediates this effect. ET-3 (10(-7) M) increased the cell surface area of cardiomyocytes after 48 h. ET-3 dose dependently (10(-9)-10(-7) M) stimulated protein synthesis as evaluated by [3H]leucine incorporation; the maximum response was 1.4-fold increase over the control at 10(-7) M. Since the response of cardiac hypertrophy is characterized by enhanced expression of fetal isoforms of muscle specific genes, the effect of ET-3 on steady state levels of mRNA for skeletal alpha-actin was evaluated by Northern blot analysis. ET-3 (10(-9)-10(-7) M) increased mRNA level for skeletal alpha-actin with a maximum response after 6 h. ET-3-induced [3H]leucine incorporation, skeletal alpha-actin mRNA and cell surface area were inhibited by a synthetic ETB receptor antagonist (BQ788). Interestingly, ET-3-induced skeletal alpha-actin gene expression and [3H]leucine incorporation were inhibited by a synthetic ETA receptor antagonist (BQ123) as well as by antisense oligonucleotides against peproET-1 mRNA. ET-3 (10(-7) M) transiently increased mRNA levels for ET-1 peaking at 30 min and stimulated the release of immunoreactive ET-1 from cardiomyocytes. These results suggest that endogenous ET-1 locally generated and secreted by cardiomyocytes may contribute to ET-3-induced cardiac hypertrophy as an autocrine/paracrine factor.

Actins↗