Biomedical subjects

H Sasano

Publications and source records attributed to H Sasano.

At least 271 records · Page 15Linked to original sources

PubMed1994

Interleukin 6-producing gastric carcinoma with fever, hypergammaglobulinemia, and plasmacytosis in bone marrow.

A 42-year-old man with a remittent fever was found to have both para-aortic and hepatic tumors with generalized lymphadenopathy. The pathological findings from biopsy specimens from the para-aortic lymph node and hepatic tumor by laparotomy and from left supraclavicular lymphadenectomy showed undifferentiated carcinoma. However, the location of the primary lesion could not be determined. Chemotherapy temporarily reduced the size of the metastatic lymph nodes and the hepatic tumor and also suppressed the remittent fever. Fifteen months after onset, massive polyclonal hypergammapathy developed together with plasmacytosis (30% plasmacytes) in bone marrow, consisting of normal mature plasmacytes. Among cytokines, including interleukin (IL) 1 beta, IL-3, IL-4, IL-6, and tumor necrosis factor alpha, a high value of IL-6 was detected in the serum. Postmortem pathological examination showed the scirrhous type of gastric carcinoma with specific staining by polyclonal antibody against human IL-6. To our knowledge, this is the first report of a gastric carcinoma producing IL-6 associated with fever, hypergammaglobulinemia, and plasmacytosis in bone marrow.

Adenocarcinoma, Scirrhous↗

PubMed1994

Immunolocalization of aromatase and other steroidogenic enzymes in human breast disorders.

Numerous studies have shown that human breast cancer tissue has the potential to synthesize estrogen through aromatization, which may act as a local growth factor of hormone-dependent cancer cells. This study was performed to localize the site of aromatization in human breast disorders by immunohistochemistry and correlate the findings with steroid receptors, clinicopathological findings, and other steroidogenic enzymes. Specimens from 60 cases of breast disorders, including 33 cases of breast cancer and 27 cases of benign proliferative disorders, were studied immunohistochemically for aromatase. In the carcinoma cases estrogen receptor (ER) and progesterone receptor (PgR) status was determined by enzyme immunoassay and immunohistochemistry, and other steroidogenic enzymes, including P450scc (side-chain cleavage), 3 beta HSD (hydroxysteroid dehydrogenase), and P450c17, were immunolocalized. Aromatase was immunolocalized in interstitial cells and adipocytes as well as other cells in both benign and malignant breast tissues. However, strong immunoreactivity was observed in adipocytes adjacent to carcinoma in all carcinoma cases and in interstitial or stromal cells around carcinomatous glands in 20 carcinoma cases. Intratumoral staining for aromatase did not correlate significantly with age, clinical stage, histopathological type, lymph nodes metastasis, or ER and PgR status. P450scc and 3 beta HSD were focally observed in 18 and 12 cases of carcinoma, respectively, but P450c17 was never observed. Aromatase expression in stromal or interstitial cells, including adipocytes, in breast cancer may be induced by carcinoma cells and locally synthesized estrogens could function as paracrine hormones. Intratumoral aromatase in human breast neoplasms correlated with malignant phenotypes but not with ER status or prognostic parameters, suggesting that other synthetic systems probably generate any biologically significant locally synthesized estrogens in hormone-dependent breast malignancy.

3-Hydroxysteroid Dehydrogenases↗

PubMed1994

Multiple transcripts of the neurofibromatosis type 1 gene in human brain and in brain tumours.

1. Neurofibromatosis type 1 is a common hereditary disorder characterized by the presence of multiple neurofibromas and café-au-lait spots, and is frequently associated with intellectual handicaps and brain tumours. The gene responsible for neurofibromatosis (the NF1 gene) codes for a protein of 2818 amino acids, termed neurofibromin, which has a domain related to mammalian ras GTPase-activating protein. 2. The NF1 gene gives rise to multiple transcripts generated by alternative splicing, that encode neurofibromin and its isoforms. These include type I mRNA coding for neurofibromin, type II mRNA coding for neurofibromin containing the insertion of 21 amino acids in the GTPase-activating protein-related related domain and mRNA coding for an N-terminal isoform lacking the GTPase-activating protein-related domain (N-isoform). 3. In the present study, the relative levels of mRNAs encoding type I, type II and N-isoform were determined by S1-nuclease mapping analysis in human brain tissue and in primary brain tumours obtained from patients with tumours unrelated to neurofibromatosis type 1. 4. These three mRNAs were expressed in all ten brain tumours and in every region of the brain examined, with the highest levels found in the cerebellum. Type I mRNA was the predominant form in the human brain except for the pons, whereas type II mRNA was predominantly expressed in eight out of ten primary brain tumours. 5. In contrast, N-isoform mRNA was similarly expressed in normal brain tissue and brain tumours. 6. These findings suggest that neurofibromin and its isoforms have important physiological roles in the human brain and that the altered expression of type I and type II mRNAs in brain tumours may be related to the tumorigenesis.

Adult↗

PubMed1994

Immunohistochemical localization of growth hormone receptor in cyclic human ovaries.

It has been demonstrated that co-administration of growth hormone (GH) augments ovarian response to human menopausal gonadotrophin, and GH itself increases steroidogenesis in cultured ovarian cells. It is not clear, however, whether the effects of GH on the ovary are direct or not. We performed immunohistochemistry using specific monoclonal antibodies against human GH receptor on 51 specimens of pre-menopausal human ovaries from various phases of the menstrual cycle to detect and localize GH receptors. Immunohistochemical localization of P450 aromatase and 3 beta-hydroxysteroid dehydrogenase was performed using these enzymes as immunohistochemical markers for steroidogenesis in these ovaries. GH receptor immunoreactivity was observed in luteinized granulosa cells in corpora lutea in the luteal phase, which are considered to be active in steroid production. In the follicular phase, GH receptor immunoreactivity was detected in the granulosa layer of only three out of 35 antral follicles. These results demonstrate that immunoreactivity of GH receptor is present in human ovaries, suggesting a direct action of GH on human ovarian functions, especially during luteal phase.

3-Hydroxysteroid Dehydrogenases↗

PubMed1994

Immunohistochemical distribution of progesterone, androgen and oestrogen receptors in the human ovary during the menstrual cycle: relationship to expression of steroidogenic enzymes.

In order to characterize immunohistochemically the possible in-situ effects of gonadal steroid hormones in the human ovary during the menstrual cycle, we immunolocalized progesterone (PR), androgen (AR) and oestrogen (ER) receptors in 50 normal cycling human ovaries, and examined the relationship between these findings and the cellular localization of steroidogenic enzymes including cytochrome P-450 cholesterol side-chain cleavage (P-450scc) enzyme, 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), cytochrome P-450 17 alpha-hydroxylase (P-450c17) and cytochrome P-450 aromatase (P-450arom). A large number of stromal cells were positive for AR, regardless of the distance from a follicle. No steroidogenic enzymes were observed in the stromal cells. In the pre-antral follicle, AR was observed in the theca cells. P-450scc, 3 beta HSD and P-450c17 were sporadically expressed in the theca cells in relatively large-sized pre-antral follicles. ER was positive in the granulosa cells only in the P-450arom-positive antral or pre-ovulatory follicle, which is likely to be a selected follicle. In the corpus luteum, in the period from ovulation to the mid-secretory phase, PR immunoreactivity was observed in a large number of both the luteinized granulosa and the theca cells. All steroidogenic enzymes were observed in all corpora lutea, but ER was negative in any corpus luteum. In the atretic follicle, AR was present in the theca interna cells. P-450scc, 3 beta HSD and P-450c17 were observed in the theca interna cells in some atretic follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗

PubMed1994

Expression of mRNA for matrix gamma-carboxyglutamic acid protein during progression of atherosclerosis in aortae of Watanabe heritable hyperlipidemic rabbits.

In an effort to characterize mRNAs that are highly expressed during atherosclerosis, we employed differential hybridization screening of a cDNA library constructed from total RNA derived from the aorta of Watanabe heritable hyperlipidemic (WHHL) rabbits. Characterizing the cDNAs for mRNAs that are present in large amounts in WHHL rabbit aortae, we identified a positive clone encoding matrix gamma-carboxyglutamic acid protein (MGP). The primary structure of rabbit MGP was deduced from nucleotide sequence analysis of the cDNA. Northern blot analysis of total RNA prepared from aortae of WHHL and normal rabbits of various ages indicated that the expression of MGP mRNA increased in proportion to the progression of atherosclerosis in WHHL rabbits. Analysis of MGP mRNA by in situ hybridization revealed that a significant amount of MGP mRNA is accumulated in atherosclerotic lesions of WHHL rabbits, suggesting that the expression of MGP mRNA is correlated with the progression of atherosclerosis.

Amino Acid Sequence↗

PubMed1994

Sex steroid biosynthesis enzymes in ovarian sex-cord stromal tumors.

Previous studies on neoplastic and hyperplastic ovarian lesions using paraffin-embedded material have demonstrated immunolocalization of sex steroid biosynthetic enzymes (SSBEs): P-450 side chain cleavage (P-450 SCC), which converts cholesterol to pregnenolone; 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), which converts pregnenolone to progesterone; P-450 17 alpha-hydroxylase and lyase (P-450 17A), which convert progesterone to 17 alpha-hydroxyprogesterone and 4-androstene-3,17-dione; and P-450 aromatase (P-450 AR), which converts 4-androstene-3,17-dione to estradiol. To investigate the utility of immunohistochemical staining for SSBEs, we studied a series of 45 sex cord-stromal tumors of the ovary. P-450 SCC was present in 9 of 11 Sertoli-stromal cell tumors, 3 of 12 granulosa cell tumors, 2 of 7 thecomas, and 1 of 1 stromal luteomas; 3 beta-HSD was present in 5 of 11 Sertoli-stromal cell tumors, 2 of 12 granulosa cell tumors, 2 of 7 thecomas, and 1 of 1 stromal luteoma; P-450 17A was present in 5 of 11 Sertoli-stromal cell tumors, 2 of 12 granulosa cell tumors, 2 of 6 thecomas, and 1 of 1 stromal luteomas; P-450 AR was present in 6 of 11 Sertoli-stromal cell tumors, 2 of 12 granulosa cell tumors, none of 7 thecomas, and 1 of 1 stromal luteoma. SSBEs were not present in 12 fibromas, one sclerosing stromal tumor, and one myxoma. Five of 45 patients with sex cord-stromal tumors showed androgenic effects; 4 of 11 patients with Sertoli-stromal cell tumors and the patient with a stromal luteoma. These five sex cord-stromal tumors contained P-450 SCC, and three of four of the Sertoli-stromal cell tumors contained 3 beta-HSD, P-450 17A, and P-450 AR. Concurrent endometrial histology was available in 25 of 45 sex cord-stromal tumor patients. None of the five sex cord-stromal tumors arising in patients with endometria that showed hyperplasia or adenocarcinoma showed immunoreactivity for SSBEs. Eight patients' endometria were unremarkable, but their sex cord-stromal tumor contained SSBEs. SSBEs were present in areas showing Leydig cell, Sertoli cell, or steroid cell differentiation or luteinized areas; however, the results did not significantly add to the histologic classification of sex-cord stromal tumors. Androgenic hormonal effects could always be explained by synthesis of hormones by SSBEs present in the patient's sex cord-stromal tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Hydroxysteroid Dehydrogenases↗

PubMed1994

Natriuretic peptides in the human kidney.

We studied the presence of three natriuretic peptides--atrial natriuretic peptide (ANP), human brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP)--in the human kidney by radioimmunoassay and immunocytochemistry. Immunoreactive ANP, immunoreactive human BNP, and immunoreactive CNP concentrations in six kidneys were 0.12 +/- 0.07 (mean +/- SD), 0.23 +/- 0.08, and 0.37 +/- 0.07 pmol/g wet wt, respectively. Sephadex G-50 superfine column chromatography and reversed-phase high-performance liquid chromatography of kidney extracts revealed a broad peak of immunoreactive ANP comigrating with ANP-28 and urodilatin. Renal immunoreactive human BNP consisted of three components; the major component comigrated with human BNP-32. Renal immunoreactive CNP consisted of at least two components; the major component comigrated with CNP-22, and the minor component eluted in a position similar to that of authentic human CNP-53. Immunocytochemistry showed that immunoreactive human BNP was colocalized with immunoreactive ANP in the segments of distal tubules, whereas immunoreactive CNP was found predominantly in the proximal tubules. These findings indicate that these three natriuretic peptides are present in the human kidney and raise the possibility that they form a renal natriuretic peptide system that participates in the local regulation of sodium and water transport and renal circulation in the human kidney.

Adult↗

PubMed1994

Quantitation of P450 aromatase immunoreactivity in human ovary during the menstrual cycle: relationship between the enzyme activity and immunointensity.

To understand changes associated with the menstrual cycle in the human ovary, it is very important to examine chronological changes in P450 aromatase (P450arom) enzymatic activity in the normal cycling ovary. Therefore, we initially examined the correlation between intensity of P450arom immunoreactivity and its biochemical enzymatic activity in five estrogen-producing human cancer cell lines (HHUA, Ishikawa, HEC-59, OMC-2, and MCF-7). P450arom immunointensity per cell was evaluated by the CAS 200 computed image analysis system, and its catalytic activity per 10(6) culture cells was analyzed by the tritiated water method. A significant correlation (r = 0.959) was demonstrated between P450arom immunoreactivity and enzymatic activity under optimal conditions of tissue fixation and immunohistochemical procedures. We then investigated P450arom immunointensity in 31 specimens of normal cycling human ovaries to examine chronological changes in P450arom activity per cell throughout the menstrual cycle. In the follicular phase, P450arom was observed in the granulosa cells of one selected antral follicle per case during the mid- to late proliferative period, and its immunointensity per granulosa cell in the follicle was not significantly different between mid- and late proliferative periods, although serum estradiol level was markedly elevated in the late proliferative period. In the luteal phase, both P450arom immunointensity per luteinized granulosa cell in a corpus luteum and serum estradiol level reached a peak in the mid-secretory period. These findings indicate that different factors may influence ovarian P450arom activity during the follicular and luteal phases, i.e., an increased number of granulosa cells in the selected follicle during the follicular phase but changes in P450arom activity per luteinized granulosa cell in the corpus luteum during the luteal phase.

3,3'-Diaminobenzidine↗

PubMed1994

Increased mRNA for CD63 antigen in atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits.

To identify a set of mRNAs that increases with the progression of atherosclerosis, differential hybridization screening of a cDNA library, constructed from total RNA in aortae of Watanabe heritable hyperlipidemic (WHHL) rabbits, was carried out. Here we report that one of the positive clones encodes a rabbit homologue of human CD63 antigen. Nucleotide sequence analysis of the cDNA revealed the primary structure of rabbit lysosomal membrane antigen CD63. Analysis of the mRNA by in situ hybridization revealed that a significant amount of the mRNA is accumulated in atherosclerotic lesions of WHHL rabbits. Northern blot analysis of total RNA prepared from aortae of WHHL and normal rabbits indicates that expression of the mRNA increased with age in WHHL rabbits, suggesting that expression of the mRNA is correlated with the progression of atherosclerosis.

Aging↗

PubMed1994

Localization of steroidogenic enzymes in adrenal cortex and its disorders.

Immunolocalization and in situ hybridization analysis of steroidogenic enzymes demonstrated the localization of steroidogenesis in the adrenal cortex and its disorders. The findings obtained provided new insights into adrenocortical hormonal metabolism, especially through establishing endocrine-pathological correlation.

Adrenal Cortex↗

PubMed1994

Cholera toxin can ADP-ribosylate Gs as well as Gi in ACTH-unresponsive human adrenocortical cancer.

It is well known that cholera toxin (CT) stimulates ADP-ribosylation of Gs and also pertussis toxin (PT) does Gi. Each GTP-binding protein has its own action in the regulation of adenylate cyclase. A human non-functioning adrenocortical cancer tissue showed an unresponsiveness in adenylate cyclase to ACTH although ACTH and CT activated adenylate cyclase in a non-functioning adrenal adenoma tissue. CT ADP-ribosylated 43 kDa protein of the plasma membrane of the cancer tissue while CT and PT could ADP-ribosylate 43 kDa and 38 kDa protein in the adenoma tissue, respectively. Immunoblotting analysis of the cancer tissue demonstrated that 40 kDa protein was detected by anti-Gs antibody as well as by anti-Gi antibody. The present experiments demonstrated that CT could ADP-ribosylate Gs which has stimulatory action on adenylate cyclase and also Gi which inhibits adenylate cyclase. Thus it is suggested that CT can activate the ADP-ribosylation of Gs and also Gi in a human adrenocortical cancer tissue, partly resulting in abnormal regulation of adenylate cyclase which may be crossly related to ACTH-unresponsiveness.

Adenoma↗

PubMed1994

Increased expression of mineralocorticoid receptor in human ileum after total colectomy: immunohistochemical and immunoblotting studies.

Aldosterone is known to regulate transmembrane ion transport and water absorption through its binding to mineralocorticoid receptor (MR) in the mammalian colon. A possible roles of aldosterone has been suggested in increased water absorption from remnant ileum in the patients with total colectomy. We, therefore, studied immunolocalization of MR in remnant ileal mucosa in the patients with total colectomy in order to study the role of aldosterone in water and sodium absorption in these patients. Immunohistochemical localization of MR was performed in ileal mucosa of 7 patients with total colectomy and 5 cases of normal ileum obtained from the resection of ascending colon due to carcinoma by using a polyclonal antibody raised against a mineralocorticoid receptor fusion protein as a primary antibody and a biotinstreptavidin system for immunostaining. Immunoblotting was also performed. Positive MR immunoreactivity was observed in both cytoplasm and nucleus of absorptive cells of ileum of total colectomy patients but not in control normal ileum. Immunoblotting revealed the presence of an approximately 100 kDa immunoreactive product corresponding to mineralocorticoid receptor. Aldosterone is considered to act on ileal mucosa following total colectomy and the aldosterone dependent sodium transport and water absorption may be accelerated in ileal mucosa after total colectomy, which is consistent with the postoperative decrease in the stool volume observed in these patients. In conclusion, increased expression of the mineralocorticoid receptor in remnant ileum may play an important role in intestinal adaptation in total colectomized patients.

Adenomatous Polyposis Coli↗

PubMed1994

[A case of ACTH-releasing lung carcinoid tumor presenting Cushing's syndrome].

The patient was a 47-year-old female who had undergone hypophysectomy due to Cushing's syndrome when 46 years old. In April 1992, about 1 month after the operation, chest CT-scan revealed a lesion of 8 x 8 mm in size in the right upper lobe. A high value of serum ACTH was obtained from the A3b wedge blood by cardiac catheterization. She was operated on suspicion of ACTH releasing lung tumor. During the operation, it was histologically diagnosed as lung carcinoid by a frozen section of the lesion. In addition, ACTH of the blood obtained from the right superior pulmonary vein was as high as 37,300 pg/ml, but that in the right main pulmonary artery or the radial artery was 850-970 pg/ml. Right upper lobectomy with dissection of mediastinal lymph nodes was so performed. Post-operative value of serum ACTH was significantly decreased. She was in good course, and is still asymptomatic 8 months after the operation.

Adrenocorticotropic Hormone↗

PubMed1994

[Periodical blood pressure variation during cardiopulmonary bypass--effects of cervicothoracic epidural anesthesia and phentolamine].

We studied the effects of cervicothoracic epidural anesthesia or intravenous phentolamine on periodical blood pressure variation during cardiopulmonary bypass in 12 adult patients undergoing open heart surgery under fentanyl anesthesia. Spontaneous periodical fluctuation of the blood pressure was analyzed by means of autoregressive power spectrum method. Amplitudes of the low frequency (0.02-0.15 Hz) component of the blood pressure variation amplitudes were calculated. The amplitudes decreased significantly 10 minutes after cervicothoracic epidural block with 15 ml of 2% lidocaine solution (P < 0.05), and after infusion of 0.4 mg.kg-1 of phentolamine (P < 0.05). Since amplitudes of the blood pressure variation were reduced by adequate epidural block or phentolamine, they are likely to reflect sympathetic vasomotor activity.

Adult↗

PubMed1994

Transforming growth factor alpha, epidermal growth factor, and epidermal growth factor receptor expression in normal and diseased human adrenal cortex by immunohistochemistry and in situ hybridization.

Because epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and epidermal growth factor receptor (EGFR) have been implicated in the regulation of adrenocortical function, we used immunohistochemistry and in situ hybridization of EGF and TGF-alpha to study 41 specimens of human adrenal cortex, including 10 normal specimens, 15 aldosteronomas, five Cushing's adenomas, six adrenocortical incidentalomas, and five carcinomas to determine what role these growth factors play in controlling human adrenocortical function. Neither immunoreactivity nor mRNA hybridization signals to EGF was detected in any specimens, and EGF therefore may exert its effects on adrenal function as an endocrine hormone. TGF-alpha expression was detected at both protein and mRNA levels in normal and neoplastic adrenal cortex, demonstrating that TGF-alpha is synthesized locally in human adrenal cortex. TGF-alpha expression was observed in the cells with increased steroidogenesis, including compact tumor cells and zona fasciculata cells with lipid depletion, but did not necessarily correlate with production sites of any specific steroid hormone. EGFR immunoreactivity was more widely distributed than TGF-alpha immunoreactivity. Both TGF-alpha and EGFR expression were markedly elevated in adrenocortical carcinomas. TGF-alpha and EGFR thus appear to be involved in biological function in both normal and neoplastic human adrenal cortex. In addition, TGF-alpha and EGFR may play important roles in some biological features of adrenocortical malignancy.

Adrenal Cortex↗

PubMed1994

DNA ploidy in human esophageal squamous dysplasias and squamous cell carcinomas as determined by image analysis.

The DNA content in cells from 98 sites from 14 surgical specimens of human esophageal carcinoma, including nonpathologic epithelium; mild, moderate, and severe squamous dysplasia and squamous cell carcinoma; and in cells from 13 sites from 13 noncancerous biopsy specimens, including nonpathologic epithelium and mild and moderate dysplasia, was determined in Feulgen-stained sections by the cell analysis system (CAS 200). In surgical specimens, diploid DNA histogram patterns were observed in 16 of 17 nonpathologic epithelia, two of seven mild dysplasias, 12 of 21 moderate dysplasias, nine of 18 severe dysplasias, six of 12 intraepithelial carcinomas, and nine of 22 advanced carcinomas. In biopsy specimens, diploid patterns were observed in four of four nonpathologic epithelia, two of seven mild dysplasias, and two of two moderate dysplasias. The remaining displayed nondiploid patterns. There was a statistically significant difference in the frequency of nondiploid histogram between nonpathologic epithelium and pathologic esophageal lesions, including squamous dysplasia and carcinoma in both surgical and biopsy specimens, but not between squamous dysplasia and carcinoma in surgical specimens. We found statistically significant differences in some parameters, including the population of cells in S-phase fraction, diploid fraction, tetraploid or higher chromosome content, and peak cell number, between nonpathologic epithelium and pathologic esophageal lesions demonstrating diploid histograms. In contrast, there were no significant differences between squamous dysplasia and carcinoma demonstrating diploid histogram in those five parameters described above.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

New concepts in the diagnosis and prognosis of endometrial carcinoma.

Several recently developed techniques have been applied to the study of endometrial lesions. These include the evaluation of K-ras abnormalities in patients with endometrial hyperplasia to identify those at high risk to develop carcinoma, the analysis of p53 abnormalities to distinguish between endometrial hyperplasia and carcinoma, the use of p53 for predicting clinical outcome in patients with endometrial carcinoma, and PCNA immunostaining of endometrial lesions with secretory activity. However, these studies should be regarded at this juncture as auxiliary, at best, to the cytological and histopathologic examination of human endometrial disorders.

Antigens, Neoplasm↗