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Biomedical subjects

H Sakaguchi

Publications and source records attributed to H Sakaguchi.

At least 19 recordsLinked to original sources

Minimal functional size of porcine lung and testicular angiotensin-converting enzymes deduced from radiation inactivation analysis. Interaction of two highly homologous domains in somatic isoenzyme.

Domain structures of porcine lung and testicular angiotensin-converting enzymes (ACE) were studied by radiation inactivation to test the hypothesis that lung ACE has two catalytic sites localized to discrete, structurally independent domains (the N- and C-domains) of approximately equal size. The minimum functional sizes of lung and testicular ACE, calculated from the inactivation curves obtained, were 140 and 74 kDa, respectively. Since testicular ACE has been demonstrated to contain only the C domain, this result indicates that the two domains in lung ACE are not independent but are, in fact, structurally tightly linked.

Animals

An analysis of proliferating cells in biopsy specimens from patients with small hepatocellular carcinoma.

The proliferation of neoplastic and nonneoplastic hepatocytes is caused by various humoral growth factors with autocrine and paracrine mechanisms, and the proliferative activity of both hepatocytes and nonhepatocytic cells contributes to neoplastic growth. The authors attempted to detect various kinds of proliferating cells immunohistochemically in small hepatocellular carcinoma (HCC) using a monoclonal antibody against DNA polymerase alpha. Most of the HCC cells that stained for this enzyme were small, had basophilic cytoplasm with poorly developed organelles, and aggregated to form clusters distributed randomly within cancer nests. Nonhepatocytic cells also were stained, including some endothelial cells, Kupffer's cells, macrophages, and lymphocytes. Fat-storing cells were not stained. The number of stained sinusoidal (capillary) cells decreased in this order: Kupffer's cells and macrophages, endothelial cells, and fat-storing cells. Nonhepatocytic cells, including lymphocytes, proliferated more actively in areas with actively growing HCC cells than in those with quiescent cancer cells. The relationship between stained HCC cells and stained sinusoidal cells was clearly defined; the correlation coefficient was 0.97. These findings suggest the possibility of a relationship between the proliferative activity of neoplastic hepatocytes and that of sinusoidal cells, including lymphocytes.

Aged

In vitro release of glutamate and aspartate from zebra finch song control nuclei.

The release of glutamate and aspartate from a song control nucleus, the robust nucleus of the archistriatum (RA) of the zebra finch was examined in slice preparations. The RA received inputs from two other song control nuclei, the high vocal center (HVc) and the lateral magnocellular nucleus of the anterior neostriatum (1MAN). The fibers that innervated the RA from either the HVc or the 1MAN caused calcium-dependent release of glutamate and aspartate after electrical stimulation. It is likely that synapses of the RA from the HVc and the 1MAN utilize glutamate or aspartate as a neurotransmitter.

Animals

Properties and localization of endothelin-1-specific receptors in rat testicles.

The characterization and localization of rat testicular endothelin receptors were studied. Receptor binding assay with radiolabeled members of the endothelin family revealed that endothelin-1-specific receptors were present in rat testes; a maximal binding capacity of 250 +/- 62 fmol/mg protein and a dissociation constant value of 0.35 +/- 0.06 nM were calculated from the Scatchard plot. The affinities for endothelin analogues were endothelin-1 = endothelin-2 much greater than endothelin-3 much greater big endothelin-1 for the membrane-bound receptors. Receptors of endothelin-1 were localized in peritubular myoid cells and interstitial cells of rat testis by 125I-labeled endothelin-1 autoradiography; the receptors were undetectable in spermatogenic cells. The presence of endothelin-1 receptors in the rat testis raises the possibility that one or more of the endothelins may play a physiological role in the regulation of testicular function.

Animals

Hypertension in unilateral atrophic kidney secondary to ureteropelvic junction obstruction.

A patient with atrophic unilateral hydronephrosis due to ureteropelvic junction obstruction associated with hypertension was successfully treated by nephrectomy. Preoperatively, plasma renin activity was elevated in both the peripheral vein and affected renal vein. Renin concentration in the resected kidney was high, and immunohistochemical localization of renin was observed along the afferent arterioles of the juxtaglomerular apparatus and in arterioles at some distance from the glomeruli.

Adult

[A case of gastric cancer with multiple liver metastasis treated with transarterial and transportal chemoembolization of tegafur/lipiodol and epirubicin].

A 56-year-old woman was admitted for advanced gastric cancer (S3H3N3P2 Stage IV). She underwent subtotal gastrectomy, left ovariectomy, and catheterization of the hepatic artery. Pre- and postoperative adjuvant chemotherapies consisting of tegafur, epirubicin, mitomycin C and cisplatin were performed. Two months after surgery, combination of transhepatic arterial and transportal chemoembolization with tegafur 400 mg/lipiodol 3 ml and epirubicin 20 mg was especially effective for this patient. The metastatic lesions of the liver regressed by 85% on computed tomography and the CEA level in the plasma decreased from 51.3 to 5.1 ng/ml. The response was judged partial response (PR), and the patient is now in good general condition.

Adenocarcinoma, Papillary

[Prognostic significance of echogenic lesion within small hepatocellular carcinoma].

To evaluate prognostic significance of echogenic lesion within small hepatocellular carcinoma (SHCC, less than or equal to 2 cm in diameter), clinical and pathological findings of 32 cases with SHCC containing echogenic lesion (echogenic SHCC) were compared with those of 55 cases with non-echogenic SHCC. Compared with the non-echogenic SHCC group, the frequency of clinical stage I was significantly higher, and there were significantly more cases with solitary tumor relative to cases with multiple tumors in the echogenic SHCC group. Histologically, the incidence of the HCC composed of well-differentiated tumor cells corresponding to Edmondson's grade I was significantly higher in the echogenic SHCC group than in the non-echogenic SHCC group. Although HCCs tended to become progressively less differentiated with increasing tumor sizes in the both groups, the process of cellular change appeared to proceed more slowly in the echogenic SHCC group. Survival rate after tumor detection was 73% at three years, 56% at five years and 48% at seven years and nine years in the echogenic SHCC group, while it was 46% at three years, 42% at five years and 0% at seven years in the non-echogenic SHCC group. The present results showed that the presence of echogenic lesion within SHCC could be useful prognostic indicator.

Aged

[Usefulness of segmental Lp-TAE using lipiodol mixed with anticancer agent for inoperable hepatocellular carcinoma].

To determine the effect of appraising subsegmental or segmental transarterial embolization with Lipiodol mixed with anticancer drugs followed by gelatin particles (Segmental Lp-TAE) on inoperable hepatocellular carcinoma, we examined CT patterns and therapeutic results in 57 patients after Segmental Lp-TAE. Fifty-six tumors including 47 tumors less than 5 cm in size were the nodular type and 1 tumor was the massive type. The mean tumor size was 3.6 cm and the mean amount of Lipiodol was 4.4 ml. Portal veins in the embolized segment were highly visualized by injected Lipiodol on plain film immediately after Segmental Lp-TAE. On the follow-up CT, the size of the tumor with dense Lipiodol accumulation were reduced in all cases, and atrophy of the embolized segment was recognized. Forty-four of the 57 patients are alive, with the longest surviving patient still alive at 4 years and 5 months. Seventeen patients have survived for more than 2 years (direct crude survival rate: 65.0%), with the cumulative survival rates 93.2% at 1 year, 71.6% at 2 years. No recurrence was recognized in 33 of the 41 patients (80.0%) that were followed up for more than 1 year after Segmental Lp-TAE is a useful therapeutic method for hepatocellular carcinoma.

Aged

Expression of intermediate filaments and other special markers by testicular germ cell tumors. With reference to embryogenesis.

Distribution of intermediate filament proteins (IFs) and several special markers was studied in 39 testicular germ cell tumors and 8 embryos and foetuses. The similarity and difference between development of germ cell tumor and embryogenesis were immunohistochemically investigated. Seminoma and embryonal carcinoma, as tumoral counterparts of undifferentiated germ cells, were characterized by little IF expression. This study revealed that the maturing and differentiating process in germ cell tumor is different from normal embryonal development and the tumor cells showed leaping maturing steps in tumorigenesis. Immunostaining for IFs helped to discover the further differentiation occurring in embryonal carcinoma and to demonstrate heterogeneous elements in non-seminoma germ cell tumors, which sometimes might not be apparent by light microscopical observation of H&E staining section. According to the findings, two patterns in mixed germ cell tumors are suggested; i.e., combined and diffuse types. The mechanism of tumorigenesis of the two types is supposed to be different. Clinically, the prognosis of most patients with testicular germ cell tumor is fairly good because of the improved chemotherapies that are dependent on histological diagnosis.

Adolescent

Analysis of proliferating hepatocytes using a monoclonal antibody against proliferating cell nuclear antigen/cyclin in embedded tissues from various liver diseases fixed in formaldehyde.

The authors studied histochemically the morphologic features of proliferating hepatocytes positive for proliferating cell nuclear antigen (PCNA/cyclin) to analyze the process of liver regeneration in embedded tissues fixed with formaldehyde using an anti-PCNA/cyclin monoclonal antibody. In liver specimens from patients with acute viral hepatitis (AVH) and confluent necrosis, many small basophilic hepatocytes surrounding large clear hepatocytes were positively stained in the areas next to the confluent necrosis. Therefore these small hepatocytes may be daughter cells derived from large clear hepatocytes that probably enter the mitotic cell cycle repeatedly to repair a large necrotic area. In the case of AVH with spotty necrosis, the positively stained hepatocytes were scattered around the necrotic foci. In the liver specimens from patients with chronic active hepatitis, most of the positively stained hepatocytes were located next to the necrotic area. As for cirrhosis of the liver, the number of hepatocytes positive for PCNA/cyclin varied greatly in different pseudolobules, and in the specimens of hepatocellular carcinoma (HCC), the HCC cells positive for PCNA/cyclin were detected throughout the cancer nests.

Antibodies, Monoclonal

Immunocytochemical identification of proliferative hepatocytes using monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin). Comparison with immunocytochemical staining for DNA polymerase-alpha.

The authors investigated whether immunocytochemical staining with a monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin) could be used to identify proliferative hepatocytes in frozen sections fixed in a mixture of periodate, lysine, and 2% paraformaldehyde. Paraffin sections also were used, which were fixed in 10% formaldehyde. Specimens of liver tissue were obtained from 27 patients with various hepatic diseases. Hepatocytes that were positive for PCNA/cyclin were observed in both types of substrate specimens. In acute hepatitis and chronic active hepatitis, most hepatocytes that were labeled for PCNA/cyclin were located near necrotic foci. However, in cirrhosis, they were detected most often near fibrotic septa; the number of immunoreactive cells varied greatly in different areas of tissue sections in such cases. In hepatocellular carcinoma, many PCNA/cyclin-positive tumor cells were seen throughout the neoplasms. Hepatocytes that were positive for DNA polymerase-alpha showed a similar distribution pattern in serial sections of study cases.

Adult

Beneficial effects of a calcium antagonist, nifedipine, on death and cardiovascular calcinosis induced by dietary magnesium deficiency in adult mice.

The effects of nifedipine on the survival rate and the cardiovascular calcinosis were investigated in dietary magnesium (Mg)-deficient mice. Male mice aged 8 to 10 weeks were fed with a diet which was either normal (0.07%) or deficient (0.007%) in Mg for 30 d. Nifedipine was added to the Mg-deficient diet for 30 d in a concentration of 1000 ppm. About 65% of Mg-deficient mice died within 30 d. In contrast, all the nifedipine-treated mice survived for 30 d. Mg-deficient mice showed hypomagnesaemia and hypocalcaemia which were not influenced by nifedipine treatment. Aortic and cardiac calcium contents increased in Mg-deficient mice, and these increments were normalized by nifedipine treatment. These results suggest that the life-saving effect of nifedipine in Mg-deficient mice might relate, at least in part, to the prevention of a deleterious increase in Ca in cardiovascular tissues.

Animals

Triacetin as food additive in gummy candy and other foodstuffs on the market.

The qualitative and quantitative analytical methods were proposed for the simple and rapid determination of triacetin (TAc) in commercial gummy candies and other foodstuffs by gas chromatography (GC), thin layer chromatography (TLC) and infrared spectroscopy (IR). Each extract from the samples was obtained by pretreatment of the foodstuffs as follows: (A) Gummy candy was dissolved in warm water and the solution was extracted with chloroform. The organic (chloroform) layer was separated. (B) Samples (such as ice cream) containing substantial water were mixed with anhydrous Na2SO4 and stirred to sandy appearance and dried. The residue was homogenized with ether, followed by centrifuging, and the organic (ether) layer was separated. (C) Dried samples (such as chocolate and cookie) were smashed, homogenized with ether, and followed by centrifuging, and the organic (ether) layer was separated. (D) Candy was dissolved in warm water and the solution was extracted with ether. The organic (ether) layer was separated. Each organic layer from (A)-(D) was washed with 10% NaHCO3 and evaporated. The residue containing TAc was dissolved in dichloromethane. The extract obtained was subjected to column chromatography on silica gel. The fractions containing TAc were employed in GC with 25% PEG-20M column, TLC, and IR analyses. Recovery of TAc from gummy candy was 99.1 +/- 3.0% and those from other foodstuffs ranged from was 82.1 to 99.4% by GC. Detection limit by this method was 10 ppm. TAc was found to contain at a level as high as 550 ppm in one domestic gummy candy. On the other hand, one imported gummy candy contained no more than 20 ppm of TAc gummy candy.

Beverages

Histological alterations in renal specimens as indicators of prognosis of IgA nephropathy.

A retrospective clinicopathological study of 66 patients with IgA nephropathy was undertaken to determine the prognostic significance of various renal histopathological alterations and clinical parameters. At the latest follow-up, after a period of 60 to 72 months following biopsy, 18 patients had serum creatinine concentration above 1.8 mg/dl. When the entire patients were evaluated as a whole, the extents of interstitial broadening and glomerular sclerosis were correlated significantly with the final status of renal function: proteinuria of more than 1.0 g per day and mildly impaired renal function at the time of biopsy were also associated with unfavourable outcome. However, when the patients with initially normal renal function, i.e. serum creatinine level below 1.2 mg/dl, were evaluated separately, the initial amount of proteinuria, but none of the other parameters, had a prognostic significance in the subsequent course of renal function. These findings suggest that proteinuria of more than 1.0 g per day as an early event often indicates the progression of IgA nephropathy, and lead to a postulation that renal histopathological changes become more significant prognostic indicators in the relatively advanced stage of the disease.

Adult

[Vasitis nodosa suspected of the spermatic cord tumor: a case report].

We report a rare case of vasitis nodosa. A 54-year-old man was found to have a right spermatic cord mass during the herniorrhaphy operation. There was no history of surgical or traumatic causes. An indurated mass in the right spermatic cord was suspected to be spermatic cord tumor, and a right high orchiectomy was performed. Histological examination revealed disruption of the ductal lumen, granulomas with the sperm-like necrotic tissue and proliferation of the lymphocytes and plasma cells in the smooth muscle bundles. Pathological diagnosis was vasitis nodosa.

Diagnosis, Differential

Developmental change of cholinergic activity in the forebrain of the zebra finch during song learning.

Song learning in the male zebra finch closely correlates with the development of song-control nuclei, the high vocal center (HVc), the robust nucleus of the archistriatum (RA) and the lateral magnocellular nucleus of the anterior neostriatum (IMAN). We previously found that acetylcholine (ACh) content increases transiently in the RA during the sensitive period of song learning. In the present experiment, development of cholinergic neurons by immunohistochemical methods using monoclonal choline acetyltransferase (ChAT) antibodies, and enzymic activity of ChAT and acetylcholinesterase (AChE) were examined in the RA during the sensitive period of song learning. The developmental change of ChAT activity in the RA was closely parallel to that of the ACh concentration. On the other hand, the density of ChAT-immunoreactive fibers changed little in the RA. This indicates that the transient increase of ACh content during the sensitive period is due to ChAT activity, but not to the increasing density of the cholinergic fibers. The ACh in the RA might be related to plastic changes in the synapse of RA neurons.

Acetylcholinesterase

Detection of proliferating liver cells in various diseases by a monoclonal antibody against DNA polymerase-alpha: with special reference to the relationship between hepatocytes and sinusoidal cells.

Proliferating cells in liver specimens from patients with various diseases were detected by use of a monoclonal antibody against human DNA polymerase-alpha, which is present in the nuclei of cells in the G1, S, M and G2 phases of the mitotic cell cycle and absent in the G0 phase, to clarify the kinetics and morphological characteristics of these cells. This monoclonal antibody was supernatant derived from clone CL22-2-42B, and the peroxidase antiperoxidase method was used. Not only epithelial cells (hepatocytes, biliary epithelial cells and hepatocellular carcinoma cells) but also nonepithelial cells (Kupffer cells and other macrophages, endothelial cells, fat-storing cells, lymphocytes and fibroblasts) were stained for DNA polymerase-alpha. In acute viral hepatitis with confluent necrosis, small hepatocytes with basophilic cytoplasm next to the necrosis accounted for most of the proliferating cells. In these areas, Kupffer cells and other macrophages and lymphocytes had often proliferated. Hepatocellular carcinoma cells were frequently stained for DNA polymerase-alpha, in addition to endothelial cells, macrophages and lymphocytes. These nonepithelial cells were stained more frequently in specimens with many stained carcinoma cells than in those with only a few cells stained. In fibrotic areas, fibroblasts were often stained for this enzyme. In proliferating bile ducts, both small epithelial cells and large mature cells were stained. The differences between stained and nonstained cells that were not hepatocytes could not be defined by their ultrastructural characteristics. From these findings, it seemed possible that sinusoidal cells, especially Kupffer cells and other macrophages, might be much involved in hepatocytic proliferation during regeneration of the liver and also in the occurrence of malignant tumors.

Adult

So-called embryonal hyperplasia of Bowman's capsular epithelium: an immunohistochemical and ultrastructural study.

The so-called embryonal hyperplasia of Bowman's capsular epithelium (EHBCE) is a rather specific lesion occurring in kidneys of patients maintained on chronic dialysis. It consists of poorly differentiated cells proliferating around sclerosed or obsolescent glomeruli. In this study, immunohistochemical and ultrastructural characterization of EHBCE was performed. The poorly differentiated cells in the lesion exhibited a positive reaction for vimentin and a negative one for cytokeratin (PKK 1) and epithelial membrane antigen. On ultrastructural examination, specialized junctions between adjoining cells, microvilli-like structures on their surfaces, and immature basal folds were observed. These observations suggest that the cells of EHBCE may be associated with the anlage of glomerular epithelium. The background in which neoplasms like renal cell carcinoma or atypical epithelium of cyst wall develop in end-stage kidneys of adult patients on long-term dialysis may cause such a proliferation of poorly differentiated cells in young or paediatric age group patients.

Child, Preschool