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Biomedical subjects

Y Kondo

Publications and source records attributed to Y Kondo.

At least 451 records · Page 25Linked to original sources

Proliferating cell nuclear antigen labeling index of preoperative biopsy specimens in gastric carcinoma with special reference to prognosis.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta and is considered to correlate with the cell's proliferative state. Immunohistochemical methods with a anti-PCNA antibody (PC10) have particular advantages compared with other techniques because of the maintenance of the tissue architecture and simplicity of the methodology. The authors investigated the correlation between the tumor's proliferative activity and progression of gastric carcinoma using immunohistochemical staining with PC10. METHODS: One hundred eighty-nine endoscopic biopsy specimens from patients with gastric carcinoma before operation were investigated by immunohistochemical study, using anti-PCNA monoclonal antibody (PC10). The correlation of PCNA labeling index (percentage of positive cells in more than 500 tumor cells) with various clinicopathologic factors and prognosis was studied. RESULTS: The PCNA labeling index became higher as the histologic stage increased. In patients with lymph node metastasis, vascular invasion, liver metastasis, and peritoneal metastasis, the labeling index was significantly higher. In patients with high PCNA labeling index (50% or greater), prognosis was significantly poorer than in those with a low index (less than 50%). The rate of disease recurrence after curative resection was significantly higher in patients with high PCNA grade group. CONCLUSION: As a result of this study, PCNA labeling index is suggested to be correlated with the depth of invasion, organ metastasis, vascular invasion, and tumor stage and to be effective as a prognostic factor.

Adult↗

Effect of vagotomy on hyperactivity and increased dopamine turnover induced by intraperitoneal administration of thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH) injected intraperitoneally at doses of 10 mg/kg and 20 mg/kg induced marked hyperactivity in rats. Although regional levels of brain dopamine and its metabolites (DOPAC and HVA) in vagotomized rats did not differ from those in sham-operated controls, the (DOPAC + HVA)/dopamine ratio, an indicator of dopamine turnover, was significantly higher in the nucleus accumbens of TRH-treated sham-operated rats than that in untreated sham-operated controls. TRH injection induced hyperactivity only in sham-operated rats and not in subdiaphragmatic bilaterally vagotomized rats. Similarly, bilateral vagotomy completely abolished the TRH-induced increases in dopaminergic turnover in the nucleus accumbens. These results suggest that the dopaminergic system in the nucleus accumbens is involved in hyperactivity induced by TRH, and that TRH mainly affects peripheral receptors. The vagal nerve may be the major pathway from the visceral organs to the brain involved in the etiology of hyperactivity.

3,4-Dihydroxyphenylacetic Acid↗

Subcellular localization of metallothionein IIA in human bladder tumor cells using a novel epitope-specific antiserum.

Human metallothioneins (hMTs) are a family of highly homologous proteins thought to be critical in cellular protection against toxins. The comparative function of individual isoforms is, however, obscure. Antibodies to individual MT isoforms might help clarify this issue but their generation has been challenging. We now describe a strategy that has successfully produced an epitope-specific antiserum to a major human isoform, hMT IIA. The immunogen, a conjugated tridecyl amino acid synthetic peptide unique to residues 8-20 in hMT IIA (AAGDSCTCAGSCK), yielded an antiserum (B2) that reacted specifically with hMT IIA in a concentration- and titer-dependent manner and showed no reactivity with human or rabbit liver MT I or horse MTs. This antiserum recognized rabbit liver MT II and, surprisingly, also reacted weakly with chicken MT. MT amino acid sequence comparisons and peptide blocking studies suggested aspartate-11 and threonine-14 are important antigenic determinants for B2. Using confocal immunofluorescence microscopy and B2 antiserum, we observed nuclear localization of hMT IIA with human bladder T24 tumor cells in exponential growth but more cytoplasmic localization at confluence. These results suggest the subcellular location of hMT IIA is a function of cell density in T24 bladder carcinoma cells. The general approach of epitope-specific antibodies may be useful for the generation of antibodies to other MT isoforms and for studying the role of individual MT isoforms in biology and toxicology.

Amino Acid Sequence↗

Postoperative chemotherapy including intraperitoneal and intradermal administration of the streptococcal preparation OK-432 for patients with gastric cancer and peritoneal dissemination: a prospective randomized study.

We studied the effects on survival time of postoperative immuno-chemotherapy, including the streptococcal preparation OK-432, in patients with gastric cancer and synchronous peritoneal dissemination. The patients were prospectively randomized and a valid statistical assessment could be made for 109. Patients randomized to group B received therapy that is widely used in Japan to treat patients with gastric cancer: mitomycin C (MMC) and UFT, a combination of tegafur and uracil in a molar ratio of 1:4, for 1 year. Patients randomized to group A received the same drugs as were given to group B patients plus OK-432 i.p. for 7 days, beginning on postoperative day 0, and OK-432 by intradermal injection for 1 year, at 2-week intervals. There were no differences between the two groups in any known prognostic factor or in the dose of any drug administered except for OK-432. There was no difference in the toxicity rate between the groups. In this negative trial, there was no improvement in survival time with the addition of OK-432 to MMC and UFT for patients with gastric cancer and peritoneal dissemination.

Aged↗

Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia.

The effects of pre-treatment with ENA-713, an acetylcholinesterase (AChE) inhibitor, on changes in pre- and postsynaptic cholinergic indices in gerbil brain following transient ischemia were studied at 4 and 14 days after recirculation. In the ischemic group, hippocampal acetylcholine (ACh) level was significantly reduced (to 23% of sham-operated controls) at 4 days post-ischemia, but this reduction was completely prevented by ENA-713 treatment. Choline acetyltransferase (ChAT) and cholinesterase (ChE) activities were not significantly changed at 4 and 14 days post-ischemia. Although the maximum number (Bmax) of muscarinic ACh receptor (mACh-R) binding in the hippocampus was decreased (to 44%) without any change in affinity at 14 days post-ischemia, this decrease was also inhibited by ENA-713 treatment. In addition, histological experiment indicated that ENA-713 inhibited ischemia-induced pyramidal cell loss in the hippocampal CA1 regions. Thus, these findings suggest that ENA-713 has protective, neurotrophic and therapeutic effects on cerebrovascular type dementia due to cerebral ischemia.

Acetylcholine↗

Long-term observations on morphological changes of choledochal epithelium after choledochoenterostomy in rats.

Morphological changes of the common bile duct were observed macroscopically and microscopically 20 months after choledochojejunostomy and choledochocolonostomy in rats. The common bile ducts were remarkably dilated in all rats of both experimental models. Choledochal stones consisting of fatty acid calcium and calcium bilirubinate were seen in two of six rats with choledochojejunostomy and two of five rats with choledochocolonostomy. The main pathological change observed in both the groups was remarkable hyperplasia of the choledochal epithelium. Only one rat with choledochojejunostomy revealed normal epithelium with choledochal stone formation. Intestinal metaplasia was seen in two rats with choledochojejunostomy and all with choledochocolonostomy. Squamous pseudostratification of the epithelium indicating atypism was observed in two rats with choledochojejunostomy. Sialomucin producing cells and sulfomucin producing cells were seen in the hyperplastic portion of the epithelium. No malignant alteration of the epithelium was detected. These findings indicate that long-lasting exposure to digestive enzymes and bacteria causes epithelial hyperplasia and further exposure to digestive enzymes plays a major role in appearance of the epithelial atypism. Carcinogenesis of the choledochal epithelium under such an environment will need much more time to be established.

Animals↗

Facilitation of copulatory behavior by pCPA treatments following stria terminalis transection but not medial amygdala lesion in the male rat.

In this study, we examined the effect of p-chlorophenylalanine (pCPA), a serotonin synthesis inhibitor, on masculine sexual behavior in male rats following bilateral medial amygdala lesions (MAL) or bilateral stria terminals cuts (STC). Males with MAL and STC both showed a suppression of sexual behavior, compared to that of sham-operated males, when injected with saline. On the other hand, intraperitoneal injections of pCPA increased mount and intromission frequencies in males with STC. Although pCPA injections also slightly increased mount frequency in males with MAL, the injections failed to affect intromission behavior in MAL males. These suggest that the stria terminalis is insufficient as pathway of a whole output of the medial amygdala in regulating copulatory behavior. The medial amygdala may be involved in some other function, such as erection, than that of the stria terminalis.

Amygdala↗

Suppression of chemically and immunologically induced hepatic injuries by gentiopicroside in mice.

Gentiopicroside (GPS), a main bitter secoiridoid constituent of roots of Gentiana macrophylla Pall., was tested for therapeutic effects on the two hepatic injury models, the CCl4-induced and lipopolysaccharide (LPS)/bacillus Calmette-Guerin (BCG)-induced hepatitides. An increase in serum level of hepatic aminotransferases (GOT: EC 2.6.1.1. and GPT: EC 2.6.1.2.) induced by a p.o. treatment of CCl4 was suppressed by pretreatment with GPS at 30-60 mg/kg/day for 5 consecutive days. An increase of these enzymes triggered by an i.v. treatment with LPS in mice primed with bacillus Calmette-Guerin (BCG) was also inhibited by GPS pretreatment at the same dose of GPS. In the BCG/LPS model, tumor necrosis factor (TNF), a major inflammatory mediator, was increased in serum with a peak at 90-120 min, followed by an increase of serum transaminase activities. GPS treatment significantly suppressed the increase of TNF in serum at the therapeutic doses, suggesting that GPS protected against hepatitis by inhibiting the production of TNF.

Alanine Transaminase↗

Up-regulation of hepatic LDL receptor gene expression by monatepil, a novel calcium antagonist, in high cholesterol diet-fed Japanese monkeys.

The action of the novel antihypertensive calcium antagonist monatepil on the hepatic LDL receptor was investigated at the gene expression level to clarify the mechanism of its hypolipidemic effect. In cholesterol-fed control monkeys, the LDL receptor mRNA level decreased to approximately 30% of that in the normal diet-fed monkeys. However, the administration of monatepil increased LDL receptor mRNA to normal levels (three- to fourfold stimulation). It is suggested that monatepil raises the number of LDL receptors in liver tissue and that this increase may accelerate the removal of plasma LDL. Treatment with prazosin, an alpha 1-adrenoceptor antagonist, also increased the LDL receptor mRNA level, but this restorative effect was much weaker than that of monatepil, suggesting that mechanisms additional to its alpha 1-adrenoceptor blocking activity are involved in the hypolipidemic effect of monatepil.

Animals↗

Calcium-dependent regulation of smooth muscle calponin by S100.

Calponin, a major calmodulin-, actin-, and tropomyosin-binding protein in smooth muscle, interacted with brain S100 and the properties of the interaction were investigated in detail. From fluorescence labeling and chemical cross-linking experiments, the apparent Kd value was calculated to be 7 x 10(7) M-1 in the presence of Ca2+ with 1 mol of S100 bound per mol of calponin. The addition of S100 to the mixture of calponin and F-actin caused the removal of calponin from actin filaments in the presence of Ca2+ but not in the presence of EGTA or Zn2+. Ca2+ and S100 could relieve calponin-induced actomyosin Mg(2+)-ATPase inhibition. Both the removal of calponin from F-actin and the restoration of ATPase inhibition by S100 were more effective than those by calmodulin. At low ionic strength, the binding was observed irrespective of Ca2+ concentration and it was greatly weakened with increasing salt concentration. The formation of the complex in the presence of Ca2+ was less sensitive, with only 45% inhibition at 100 mM NaCl, where the complex in the absence of Ca2+ had almost disappeared. This was confirmed by S-100 Sepharose 4B chromatography. Addition of Ca2+ and S100 also led to a decrease in the affinity of calponin for tropomyosin. Domain mapping with chymotryptic digestion revealed that the S100 binding site resided within the N-terminal 22 kDa fragment of calponin, where the bindings of calmodulin and actin also occur.

Actins↗

Malignant melanoma within an intradermal nevus.

We describe a case of malignant "dermal" melanoma that arose within a preexisting intradermal nevus. Clinically, the lesion had recently enlarged. Histologically, two patterns were noted. One was an intradermal nevus in the upper portion of the dermis; the other was a deeper nodule composed of malignant neoplastic cells that extended into the reticular dermis. No melanocytic epidermal junctional activity was noted. Despite careful clinical investigation, no alternative primary source was found. Neoplastic transformation of the intradermal nevus without junctional activity is our proposed interpretation of the lesion's histology. Immunohistochemical stains demonstrated that the deeper dermal neoplastic cells were positive for both HMB-45 and PCNA, whereas the superficial nevoid-appearing cells were negative; these findings support our postulate that this melanoma arose within an intradermal nevus. It is important to distinguish this neoplasm from other diagnostic possibilities, including a metastatic lesion originating from another site.

Aged↗

Photoreceptor differentiation of retinoblastoma: an electron microscopic study of 29 retinoblastomas.

Retinoblastomas exhibit a unique form of differentiation to produce cell elements similar to those seen in a photoreceptor cell. An ultrastructural study was performed on 29 cases of retinoblastoma to further clarify the cytologic characteristics of the tumor cells. The age of the retinoblastomas averaged 17.1 months and the tumor cells showing photoreceptor differentiation were demonstrated in 10 cases (35%). The findings were especially notable in retinoblastomas with Flexner-Wintersteiner rosette formation (seven cases, 28%). Similar photoreceptor differentiation was also evident in solid cell clusters without rosette formation (four cases, 14%). The presence of photoreceptor elements was assumed to be significantly frequent both in Flexner-Wintersteiner rosettes and in the solid cell clusters. The cell cytoplasm also showed proliferation of long mitochondria and microtubules, reflecting photoreceptor differentiation. The hereditary-type retinoblastoma showed more advanced cell differentiation than the non-hereditary type. Photoreceptor differentiated retinoblastoma showed rather indolent growth compared with the undifferentiated type, and the former can expect a curative treatment by operation. These observations provide additional findings of the biological nature of retinoblastomas.

Cell Differentiation↗

Modulation of cytoskeletal organization of podocytes during the course of aminonucleoside nephrosis in rats.

By immunoelectron microscopy the modulation of cytoskeletal organization of podocytes during the course of puromycin aminonucleoside-induced nephrosis was examined. In control rats, tubulin and vimentin were present, limited to the podocyte cell body and the major processes. Their distribution in the foot processes was virtually negative. Myosin exhibited the same distribution pattern, albeit much more scattered, with no relation to any podocyte organelles or cell structures. Actin was scattered over the fibrillar zones of the cell body and its processes, including the foot processes. In proteinuric rats, loss of foot processes occurred and the glomerular basement membrane was covered by broad cytoplasmic sheets of podocytes, which contained these four subunits of cytoplasmic filaments. Accompanied by the disappearance of proteinuria, the structural organization of the foot processes was completely restored, in which tubulin, vimentin, and myosin were scarcely observed. Our results confirmed that the loss of foot processes is caused by their retraction, and indicated that the specific localization of the podocytic cytoskeleton contributes to the maintenance of the particular cell shape. Its reorganization may account for the structural modification of podocytes.

Actins↗