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Biomedical subjects

T Akamatsu

Publications and source records attributed to T Akamatsu.

At least 19 recordsLinked to original sources

Proliferative markers in gastric carcinoma and organoid differentiation.

The present study was undertaken to elucidate the relationship between the distribution of potentially proliferative tumor cells and the organoid differentiation of tumor cells in gastric carcinomas. One hundred four specimens of surgically removed human gastric carcinomas, including 68 and 36 specimens of early and advanced carcinomas, respectively, were studied by using a battery of histochemical techniques. Serial 3-microns thick paraffin sections were stained by galactose oxidase-cold thionine Schiff-paradoxical concanavalin A staining (GOCTS-PCS), or were immunostained for pepsinogen types I and II, lysozyme, and proliferating cell nuclear antigen (PCNA). In addition, to identify proliferative tumor cells parts of fresh carcinoma tissues were incubated in a solution containing bromodeoxyuridine (BrdU), embedded in paraffin, and immunostained for BrdU. The results indicated that in intramucosal carcinoma tissues showing organoid differentiation the proliferative tumor cells were located predominantly between the covering epithelial cell type tumor cells and the glandular mucous cell type tumor cells, and the disturbance in the distribution of proliferative cells coincided with the submucosal invasion.

Biomarkers, Tumor

Characterization of development-specific, cell type-specific mouse testicular antigens using testis-specific polyclonal antibodies.

Antisera were raised by immunizing rabbits with mouse testicular germ cells, and absorbed in vivo by injection into castrated male whole mice to obtain a specific antiserum which reacted with mouse germ cells. The expression of mouse testis-specific antigenic macromolecules was then studied immunochemically with the antiserum. Approximately 20 antigenic macromolecules with molecular weights ranging from 26 to 110 kD were detected in the normal adult testis. At least 12 of these were differentiation-specific antigens appearing during development of germ cells, while others were expressed in testicular germ and/or somatic cells or detected only in mature spermatozoa. This technique for raising testis-specific antisera could be useful for isolation of cDNA clones encoding their antigens, as well as for investigation of the physiological roles of these molecules in germ cell differentiation at the molecular level.

Animals

Distribution of the Kexin family proteases in pancreatic islets: PACE4C is specifically expressed in B cells of pancreatic islets.

The distribution of Kexin family proteases in adult rat pancreatic islets was investigated by immunohistochemical means using a series of specific antibodies specific for PC1, PC2, PC6, Furin, PACE4A and a recently identified member of the Kexin family, PACE4C. PACE4C expression was limited to B cells of the pancreatic islets. PC2 was found in A and in some D cells more than in B cells and PC1 was evident only in B cells. Furin and PC6 were weakly and evenly expressed in the entire islet. PACE4A was hardly found in the islets. These findings indicated that individual Kexin family proteases are uniquely distributed in the islets and suggested that these proteases share roles in these cells as follows: PC2 is involved in the peptide hormone precursor processing in A cells and in D cells, and PACE4C, PC1 and PC2 (mainly PACE4C and PC1) are responsible for the processing event(s) specific to B cells.

Animals

[Clinical and etiological studies of IgG antibodies to Helicobacter pylori detected by enzyme-linked immunosorbent assay].

Recently, Helicobacter pylori (H. pylori) has been reported that it is involved in the pathogenesis of duodenal ulcer and might be a risk factor for gastric cancer. To diagnose H. pylori infection, detection of serum antibody is much less stressful and more cost effective than gastric biopsy. Using a serological method, We have reported that the prevalence of serum anti-H. pylori IgG was elevated with age among healthy subjects and over 80% among elder people. Thus, it would be essential to investigate the specificity of the ELISA system (PirikaplateG Helicobacter) for the detection of serum anti-H. pylori IgG. Sera from healthy controls (n = 653) and patients (n = 116) with gastritis, gastric ulcer, and/or duodenal ulcer were studied for anti-H. pylori IgG. Cross reactivity of the anti-H. pylori IgG with closely related bacteria was less than 10% (with C. jejuni: 7.4%, C. laridis: 0.2%, E. coli: -2.4%) in the ELISA system. Anti-H. pylori IgG from both normal controls and the patients were equally neutralized with the extract of H. pylori. Of note was that the prevalence of anti-H. pylori IgG among patients was significantly higher than that among normal controls. Referring to the diagnoses by gastric biopsy, the sensitivity and specificity of this ELISA were 88.2% and 74.2%, respectively. We also demonstrated the clinical usefulness of this ELISA by receiver operating characteristic curve (ROC). Interestingly, several healthy subjects positive for serum anti-H. pylori IgG were voluntarily subjected to gastric biopsy, and proved positive for H. pylori infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Identification of targeting proteinase for rat alpha 1-macroglobulin in vivo. Mast-cell tryptase is a major component of the alpha 1-macroglobulin-proteinase complex endocytosed into rat liver lysosomes.

The alpha 1-macroglobulin-proteinase complex endocytosed into rat liver lysosomes was purified by a series of column chromatographic steps on concanavalin A-Sepharose, Sephacryl S-300, DEAE-cellulose and TSK gel DEAE-5PW columns. The complex contained no detectable alpha 2-macroglobulin. Studies on the substrate specificity indicated that the complex had tryptase-like activities towards various synthetic substrates, but no elastase, chymotrypsin, cathepsin-B and cathepsin-L activities. The proteinase activity was completely inhibited by di-isopropyl fluorophosphate, leupeptin and antipain, indicating that the proteinase bound to alpha 1-macroglobulin is a serine proteinase. Two protein bands (62 and 59 kDa) of the complex were labelled with [3H]diisopropyl fluorophosphate and both bands cross-reacted with anti-(mast-cell tryptase)antibody. These results suggest that mast-cell tryptase is a major targeting proteinase for alpha 1-macroglobulin in vivo. The main alpha-macroglobulin-proteinase complex in the adjuvant-treated rats was also the alpha 1-macroglobulin-tryptase complex, even though the plasma level of alpha 2-macroglobulin was elevated.

Amino Acid Sequence

Pigmentary retinopathy with nephrotic syndrome, Ménétrier's disease, and diabetes mellitus.

A patient with pigmentary retinopathy, nephrotic syndrome, Ménétrier's disease, and diabetes mellitus is presented. Other complications were congestive heart failure, hypothyroidism, hypertension, and hypertriglyceridemia. Hypogenitalism was also suspected. Pigmentary retinopathy is known to associate with many systemic diseases, which are classified into several syndromes. This case superficially resembles Alström's disease due to the common characteristics of pigmentary retinopathy, diabetes mellitus, renal disease, and hypogenitalism. But clinically and histologically, there are distinct differences. To our knowledge, this association has never been reported.

Consanguinity

Localization of peroxidase activity in tegumental, muscle, and parenchymal cells of the lung fluke Paragonimus miyazakii (Digenea: Troglotrematidae).

The distribution and localization of peroxidase activity were examined in adults of Paragonimus miyazakii in sections stained with 3,3'-diaminobenzidine in the presence of hydrogen peroxide. Peroxidase activity was detected in tegumental cell mitochondria. With cell development, the reaction intensity became greater. Activity extended from the inner membrane (undifferentiated stage) to the intermembrane space (differentiating stage) and then to the matrix (differentiated stage). Mitochondria with the most intense reaction were densely distributed in the outer syncytial region. Strong activity was also present in mitochondria of muscle cells and in those of Type II parenchymal cells. Intermembrane spaces were the predominant site of this activity. Characteristically, both 10 mM azide and 1 mM cyanide were mildly effective in the inhibition of mitochondrial peroxidase activity in each cell type.

3,3'-Diaminobenzidine

Establishment of Epstein-Barr virus-associated lymphoma cell line SUBL with t(2;3)(p11;q27) from a liver transplant patient.

A new lymphoma cell line, designated SUBL, was established from a Japanese patient with Epstein-Barr virus (EBV)-associated lymphoma, which developed during FK 506 therapy after liver transplantation. This cell line has undergone 80 passages over a period of 22 months. The cultured cells were positive for CD19, CD20, CD21, CD22, CD23, and HLA-DR, and negative for CD10 and surface immunoglobulins. Immunoglobulin gene analysis revealed rearrangements of JH and JK. T-cell antigens or T-cell receptor gene rearrangements were not observed on the cell line. The SUBL cells were positive for Epstein-Barr virus nuclear antigen (EBNA). The EBV genome was detected in the original tissue and the cell line by the in situ hybridization method. These data indicate that this cell line represents the B-cell lineage at a pre-B-cell stage. SUBL cells showed successful heterotransplantation to mice with severe combined immunodeficiency (SCID). Chromosomal analysis revealed the karyotype 46,XY,t(2;3)(p11;q27). Molecular studies showed that c-myc, N-myc, and bcl-2 were not rearranged. This cell line will provide a useful in vitro system to study the relationship between chromosomal abnormalities and the activation of cellular oncogenes.

Animals

Mucin histochemistry of pancreatic duct cell carcinoma, with special reference to organoid differentiation simulating gastric pyloric mucosa.

The present study was undertaken to explore mucins produced in normal, metaplastic, and hyperplastic ductal epithelia as well as in carcinoma tissues of the pancreas, and used a battery of histochemical techniques. Thirty-five cases of ordinary pancreatic duct cell carcinoma and nine cases of duct cell carcinoma, which fulfilled the clinical criteria of "mucin-producing carcinoma of the pancreas," were examined. The results indicated that all lesions of mucinous metaplasia with or without papillary hyperplasia as well as atypical hyperplasia characteristically had gastric mucins and showed organoid differentiation simulating the gastric pyloric mucosa, but never stained for 8-O-acetyl-N-acetylneuraminic acid, which is a histochemical marker of the large intestine. Ordinary duct cell carcinoma also contained gastric mucins and small intestinal mucins and showed organoid differentiation, but rarely had 8-O-acetyl-N-acetylneuraminic acid. Mucin-producing carcinomas were classified into two groups: the ordinary duct cell carcinoma group and a group that showed marked atrophy and extensive fibrosis of the parenchyma, a lack of organoid differentiation and gastric mucins, and an abundance of large and small intestinal mucins. These results suggest that gastrointestinal mucins are useful markers to detect cancer-related lesions and cancers of the pancreas.

Adult

Menopause related changes of adrenocortical steroid production.

To elucidate changes of adrenocortical steroid production with age, reproductive age (n = 14), peri-menopausal (n = 12) and post-menopausal (n = 13) women were studied using basal hormone levels and the results of a rapid ACTH stimulation test. Peripheral serum levels of pregnenolone, 17 alpha-hydroxypregnenolone, 17 alpha-hydroxyprogesterone, dehydroepiandrosterone and androstenedione were measured by RIA. The basal levels of all steroids except pregnenolone decreased with age. A significant increase in the levels of all steroids after ACTH stimulation was observed in all subjects. Although, there was an age related decrease in the response of C19-steroids to ACTH, the response of pregnenolone and 17 alpha-hydroxyprogesterone to ACTH did not alter with age. The preserved response of 17 alpha-hydroxyprogesterone to ACTH in post-menopausal women suggests that 17 alpha-hydroxyprogesterone production plays a role in the age independency of cortisol. In the present paper, the changes in the capacity of the post-menopausal adrenal cortex to produce androgens and C21-steroids were demonstrated.

17-alpha-Hydroxypregnenolone

Al-type generalized amyloidosis showing a solitary duodenal tumor.

An amyloid tumor of the duodenum is a rare occurrence. A patient who presented with epigastric discomfort, in whom a barium meal study revealed a tumor of the duodenum is described. Upper gastrointestinal endoscopy showed a submucosal location of the tumor, and examination of a biopsy revealed amyloid deposition of the AL type. Diffuse tumor involvement of adjacent tissues of the duodenum and also deposits of amyloid fibrils in the liver and skin with no evidence of a chronic pre- existing disease in the patient led to the diagnosis of primary systemic amyloidosis. The distinguishing feature of this case was the formation of a solitary and relatively large tumor in the duodenum mimicking a submucosal tumor, which is in contrast to most reported cases of multiple and smaller amyloid tumors in other parts of the gastrointestinal tract.

Amyloidosis

In vitro closing behavior of the St. Jude Medical heart valve in the pulmonary position. Valve incompetence originating in the prosthesis itself.

We examined the in vitro closing behavior of the St. Jude Medical heart valve, simulating (1) a low-pressure system, (2) the anatomic peculiarity of the right ventricular outflow tract and the main pulmonary artery, and (3) disturbed diastolic compliance of the right ventricle. The variables in the experiment were the load impedance to the pump and the valve orientation. The results were as follows. The sequence of closure of the two semidiscs was based on the valve orientation; reduction in impedance caused the semidisc that closed last to remain open, while the other semidisc continued its open-close motion; further reduction in impedance prevented the semidisc, which continued its open-close motion, from closing completely. These results highlight the forces involved in semidisc closure and the existence of a threshold of force for completion of semidisc closure. Further, the results demonstrate that under certain circumstances the threshold cannot be exceeded via those forces. Therefore this incompetence must originate in the prosthesis itself. In this regard, we suggest an urgent need to reconsider the indications for St. Jude Medical heart valve pulmonic implantation. Finally, we advocate the necessity for an in vitro assessment of valve prostheses in a low-pressure system, to evaluate the safety of right-sided placement.

Evaluation Studies as Topic

[Changes in steroid enzyme activities with age in human ovary].

It is well documented that sex hormone secretion decreases as age advances. In this study, 17 alpha-hydroxylase (17hy), 20 alpha(beta)-hydroxy steroid dehydrogenase (20-HSD), C17-20 lyase, 17 beta-hydroxy steroid dehydrogenase (17 beta-HSD) and aromatase activities in ovarian tissues were examined in order to study the changes in steroid metabolism in human ovary with age. Tissues were obtained from women aged 30-81 years who had undergone gynecological laparotomy. Enzyme activities were measured by the conversion of 14C-labeled progesterone, 17 alpha-hydroxy progesterone and androstenedione to amounts of corresponding labeled products. Remarkable reduction of C17-20 lyase and 17hy activities were noticed in the ovaries obtained from the women in the premenopausal stage when the activities were compared with those from reproduct women. However, the activities of aromatase, 17 beta-HSD and 20-HSD were not changed. Further, a decrease of 17hy activities was observed in the ovaries obtained from menopausal women. Aromatase activity was also reduced at this stage while the 17 beta-HSD and 20-HSD remained unchanged. In addition, the formation of 17 alpha, 20 beta-OH-P4 from 17P4 was first demonstrated indicating that activity of 20 beta-HSD in postmenopausal ovary and found to be localized in the microsomal fraction. These result indicated that the changes of ovarian steroid enzyme activities with age were characterized by a striking reduction in C17-20 lyase and 17hy activities while 17 beta-HSD and 20-HSD activities were not impaired. Aromatase activity was found to be decreased in ovaries at menopause.

17-Hydroxysteroid Dehydrogenases

Adenocarcinoma of the cervical oesophagus arising from ectopic gastric mucosa. The histochemical determination of its origin.

A case of adenocarcinoma of the cervical oesophagus was examined by employing a battery of histochemical techniques and was demonstrated to arise from ectopic gastric mucosa. The patient was a 66-year-old Japanese male. Endoscopy revealed an ulcerated tumour on the right anterior wall of the cervical oesophagus, approximately 16 cm from the incisor teeth. Pathological examination of surgically removed specimens showed well-differentiated tubular adenocarcinoma. Ectopic gastric mucosa was found in the oesophageal mucosa adjoining the carcinoma. Histochemical stains for characterizing mucosubstances and immunostains for various antigens were used. In addition to this carcinoma, ectopic gastric mucosa in the oesophagus and normal oesophageal, cardiac, tracheal and bronchial mucosa were also examined. The results showed that the carcinoma contained mucins, which showed reactivities characteristic of the gastric surface mucous cell (galactose oxidase-cold thionin Schiff reactive) and gland mucous cell (paradoxical concanavalin A staining reactive). Ectopic gastric mucosa consistently contained these mucins, but other tissue sites lacked them.

Adenocarcinoma

Effect of alcohol on blood levels of branched-chain alpha-keto acids in male Wistar rats.

The effect of oral alcohol administration on branched-chain alpha-keto acids was studied in Wistar rats. Rats were divided into alcohol loading groups 1 (ethanol single daily dose: 2.5 g/kg body wt for 14 days) and 2 (ethanol dose: 5 g/kg body wt), and a pair-fed control group (isocaloric glucose and food equal to the amount taken by group 1 the previous day). Branched-chain alpha-keto acids, other alpha-keto acids and amino acids were analysed using high-performance liquid chromatography. Results showed a significant body weight increase in the alcohol loading groups. Concentrations of branched-chain amino acids and keto acids were significantly increased in the alcohol-treated groups. The blood levels of methionine, threonine, alanine and glutamic acid were also increased by alcohol administration. Blood levels of taurine and ornithine, however, showed a significant decrease in the alcohol-treated groups. These results show that alcohol increases the blood levels of branched-chain keto acids and branched-chain amino acids.

Alcohol Drinking

[Relations of serum apolipoprotein A-I, A-II and B levels to smoking, drinking and body mass].

To examine whether the serum apolipoprotein A-I level (Apo A-I), serum apolipoprotein A-II level (Apo A-II) and serum apolipoprotein B level (Apo B) are related to cigarette-smoking habits, drinking frequency and body mass index (BMI) independent of serum lipoprotein cholesterol levels (HDLC, LDLC or VLDLC), we statistically analyzed the data on Apo A-I, Apo A-II, Apo B, HDLC, LDLC and VLDLC and the life style data obtained from health examinations of 256 male residents aged 40 to 49 mostly randomly selected from two Japanese areas, Ninohe, Iwate and Ishikawa, Okinawa. The results were as follows: (1) HDLC was strongly positively correlated with Apo A-I and Apo A-II, while Apo B was strongly correlated with LDLC and VLDLC. (2) According to univariate analyses, Apo A-I, Apo A-II, Apo B, HDLC, LDLC and VLDLC were not associated with smoking. On the other hand, drinking frequency was positively associated with Apo A-I, Apo A-II and HDLC. Apo A-I and HDLC were negatively correlated with BMI, whereas Apo B, LDLC and VLDLC were positively correlated with BMI. (3) According to the results of multi-dimensional analyses of covariance, Apo A-II was positively correlated with drinking frequency independent of Apo A-I and HDLC, especially among the individuals with increased HDLC. The same multivariate analysis showed that Apo B was positively associated with smoking independent of LDLC and VLDLC among the individuals without increased VLDLC. From these results, we conclude that Apo A-II may be effective as a biological marker for alcohol drinking independent of Apo A-I and HDLC, while cigarette smoking may affect Apo B through a certain direct mechanical effect. (4) Increased HDLC in obese individuals (BMI greater than or equal to 27) or non-drinkers was associated with remarkably increased Apo A-I, while decreased HDLC in thin individuals (BMI less than 21) was associated with remarkably decreased Apo A-II.

Adult

Epidemiology of glaucoma in Japan--a nationwide glaucoma survey.

A population-based, collaborative glaucoma survey was conducted in seven regions throughout Japan, during the years of 1988 and 1989. The total number of subjects examined was 8,126 out of 16,078 residents aged 40 years or older, representing a participation rate of 50.54%. There were no significant differences in background factors between participants and randomly sampled nonparticipants. A mainstay of the screening consisted of tonometry and fundus photography with nonmydriatic camera, followed by automatic perimetry as a recall examination. Overall prevalences obtained were primary open-angle glaucoma (POAG) 0.58%, low-tension glaucoma (LTG) 2.04%, primary angle closure glaucoma (PACG) 0.34%, other types of glaucomas 0.60%, and ocular hypertension (OH) 1.37% at the time of screening. The very high prevalence of LTG and extremely low prevalence of OH in the Japanese might reflect a racial peculiarity in the age-specific trend of the intraocular pressure. The prevalence of PACG was found much higher in Japanese than in Caucasians, with a predilection for women. Racial peculiarities as revealed in this study were discussed, with particular reference to the refractive status in the Japanese that showed progressive decrease in myopia with age.

Adult