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Biomedical subjects

T Hori

Publications and source records attributed to T Hori.

At least 19 recordsLinked to original sources

[A case of Cushing's disease associated with a non-functioning adrenal tumor].

A 52-year-old woman was admitted to our hospital for further examination of central obesity, hypertension and hirsutism suggesting Cushing's syndrome. Hirsutism had been remarkable for two years, and muscle weakness of the lower extremities gradually developed during the past year. CT scan revealed a tumor in the left adrenal gland which was 1 cm in diameter, round, well-circumscribed, homogeneous and not enhanced. Endocrine data disclosed increased urinary 17-OHCS (11.5-16.4 mg/day) and elevated plasma ACTH (125 pg/ml) and cortisol (19 micrograms/dl) with a lack of diurnal rhythm. Administration of the single-dose dexamethasone (1mg) did not suppress plasma cortisol. However, consecutive administration of either 2mg or 8mg of dexamethasone for 2 days suppressed both plasma cortisol and urinary 17-OHCS. Administration of metyrapone raised both urinary 17-OHCS and plasma ACTH levels. Rapid ACTH test resulted in a hyperresponse of plasma cortisol. CRF injection raised plasma ACTH and cortisol. Bilateral adrenal glands were well demonstrated by 19-iodocholesterol (I-131) scintigraphy during the administration of dexamethasone. MRI with Gd-contrast revealed a microadenoma in the sella turcica. With the diagnosis of Cushing's disease, the microadenoma was removed by the transsphenoidal approach and adrenal function was normalized. However, the left adrenal tumor remained on CT scan but was not demonstrated by scintigraphy. These findings indicate that this is a very rare case of Cushing's disease which was associated with an unilateral non-functioning adrenal tumor.

Adenoma

Polar glycosphingolipids in annelida. A novel series of glycosphingolipids containing choline phosphate from the earthworm, Pheretima hilgendorf.

A novel series of glycosphingolipids containing choline phosphate has been demonstrated in whole tissues of the earthworm, Pheretima hilgendorfi. The thin layer chromatographic pattern of the total polar glycolipids revealed the presence of more than three components with positive reactions toward orcinol-sulfuric acid (sugar), molybdate (phosphate), and Dragendorff's (choline) spray reagents. Two of these polar glycolipids (PGL1 and PGL2) were purified by the use of successive column chromatography on QAE-Sephadex A-25 and silicic acid (Iatrobeads) and detected during elution by the presence of galactose-bound choline phosphate. The structural elucidation of the oligosaccharide moieties was performed by compositional sugar analysis, hydrogen fluoride degradation, proton magnetic resonance spectroscopy, fast atom bombardment mass spectrometry, and methylation analysis. Thus, the structures of PGL1 and PGL2 were deduced to be as follows: cholinephosphoryl-->6Gal beta 1-1Cer and cholinephosphoryl-->6Gal beta 1-6Gal beta 1-1Cer. Although the oligosaccharide structures of both PGL1 and PGL2 have previously been found in other organisms, the presence of a choline phosphate group as an oligosaccharide substituent is the first finding in nature. The main molecular species of the ceramide moieties were composed of beheninyl- and lignocerinyloctadecasphingenines and their nonadecasphingenine homologues.

Animals

Pseudo-high affinity interleukin 2 (IL-2) receptor lacks the third component that is essential for functional IL-2 binding and signaling.

Functional studies of the interleukin 2 receptor (IL-2R) of two (ED515-D and Kit225) IL-2-dependent and three (ED515-I, 3T3-alpha beta 11, and Hut102) IL-2-independent cell lines were done. All of these cell lines appeared to express high as well as low affinity IL-2R. However, ED515-I and 3T3-alpha beta 11, which expressed the IL-2R beta chain, did not bind IL-2 at all when IL-2 binding to their IL-2R alpha chain was blocked with anti-Tac monoclonal antibody, whereas the intermediate affinity binding in ED515-D, Kit225, and Hut102 cells remained. We tentatively called the high affinity IL-2R of the former cells pseudo-high affinity IL-2R. The dissociation constant of pseudo-high affinity IL-2R was higher than that of ordinary high affinity IL-2R. Internalization of cell-bound 125I-IL-2 into ED515-I and 3T3-alpha beta 11 cells was less efficient than that into ED515-D cells. The addition of IL-2 neither promoted cell growth nor upregulated IL-2R alpha chain expression in ED515-I and 3T3-alpha beta 11 cells. Furthermore, tyrosine phosphorylation of the cellular proteins (p120, p98, p96, p54, and p38) was induced or enhanced in response to the addition of IL-2 in ED515-D and Kit225 cells, but not in the cell lines expressing pseudo-high affinity IL-2R. Finally, 125I-IL-2 crosslinking followed by SDS-PAGE analysis showed an 80-kD band corresponding to p65 + IL-2, in addition to bands corresponding to IL-2R alpha and beta chain + IL-2 in cells bearing ordinary high affinity IL-2R but not in cells with pseudo-high affinity IL-2R. Taken together, we consider that another protein whose molecular mass is approximately 65 kD is functionally important in IL-2 binding and subsequent signal transduction and may be the third component of IL-2R.

3T3 Cells

Human fetal liver-derived CD7+CD2lowCD3-CD56- clones that express CD3 gamma, delta, and epsilon and proliferate in response to interleukin-2 (IL-2), IL-3, IL-4, or IL-7: implications for the relationship between T and natural killer cells.

Cells from fetal liver or fetal and adult bone marrow that are membrane (m)CD3 negative and have not rearranged TCR genes but express CD3 proteins in their cytoplasm are considered to be committed T-cell progenitors. Recent findings question whether CD3 is T-cell specific because fetal natural killer (NK) cells have been shown to express cCD3 delta and epsilon proteins. To further examine the relationship between T and NK cells, we generated mCD3-cCD3+ clones from fetal liver. Two stable clones, FL412 and FL508, isolated from different donors, were selected on the basis of absence of the NK cell marker CD56. These clones shared a common phenotype of CD7+CD2lowCD3-CD4-CD8-CD5-CD6-CD11b+CD16-CD56 -. Like fetal NK clones, these clones expressed cytoplasmic CD3 delta and epsilon transcripts and proteins. However, the clones exhibited no or very low levels of cytotoxic activity against K562, JY, or Daudi, which were lysed efficiently by fetal NK clones. TCR beta, gamma, and delta genes in these clones were in germline configuration. Furthermore, both FL412 and FL508 responded not only to interleukin-2 (IL-2), IL-4, or IL-7, but also to IL-3 with proliferation. These results suggest that FL412 and FL508 retained some characteristics of a putative T or NK precursor in the fetal liver and may be useful for analyses of this poorly defined cell type.

Antigens, CD

Effects of glycine antagonists on Mg(2+)- and glycine-induced [3H]N-(1-[2-thienyl]cyclohexyl)-3,4-piperidine binding.

We investigated the effects of glycine antagonists, 3-amino-1-hydroxy-2- pyrrolidone (HA-966), 7-chlorokynurenic acid (7-Cl-KYNA), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 6,7-dichloro-3-hydroxy-2-quinoxalinecarboxylic acid (DHQXC), 6,7-dichloroquinoxaline-2,3-dione (DCQX), and 5-chloro-indole-2-carboxylic acid (5-Cl-I2CA), on Mg(2+)- and glycine-induced [3H]N-(1-[2-thienyl]cyclohexyl)-3,4-piperidine ([3H]TCP) binding to well-washed rat cortical membranes. Except for 5-Cl-I2CA, all the glycine antagonists completely inhibited not only glycine- but also Mg(2+)-induced [3H]TCP binding in a concentration-dependent manner. Out of all the glycine antagonists examined DHQXC most selectively inhibited Mg(2+)-induced [3H]TCP binding, while DCQX was the most selective for inhibiting glycine-induced [3H]TCP binding.

Animals

Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic function and express cytoplasmic CD3 epsilon,delta proteins.

Natural killer (NK) cells have been defined as CD3 epsilon-, CD16+ and/or CD56+ lymphocytes that mediate major histocompatibility complex (MHC)-unrestricted cytotoxicity against certain tumors and virus-infected cells. Unlike T lymphocytes, NK cells do not rearrange or productively express T cell antigen receptor genes. Moreover, NK cells from adults have been reported to not express CD3 gamma, delta, or epsilon proteins on the cell surface or in the cytoplasm. Nonetheless, NK cells have been shown to share a number of antigenic and functional similarities to T cells that suggest the possibility of common origins. In this report, we demonstrate that functional NK cells exist in liver at early stages of human embryonic development. Freshly isolated fetal NK cells mediated MHC-unrestricted cytotoxicity against NK-sensitive targets and acquired the ability to lyse NK-resistant tumors after overnight culture in interleukin 2. Unlike adult NK cells, freshly isolated fetal liver NK cells and clones derived from these cells, as well as a subset of cord blood NK cells, express substantial levels of CD3 delta and CD3 epsilon proteins in the cytoplasm. Expression of CD3 epsilon and CD3 delta transcripts and cytoplasmic proteins in fetal NK clones was confirmed by polymerase chain reaction and Western blot analysis. These findings support the concept that NK and T cells may arise from a common progenitor that expresses components of the CD3 complex. Alternatively, it is possible that the cytoplasmic CD3 delta, epsilon+ fetal NK cells represent a distinct subpopulation of NK cells that is predominant in the fetus, but replaced by the cytoplasmic CD3 delta,epsilon- adult NK cell population after embryogenesis.

Antigens, CD

Effects of long-term anticonvulsant therapy on copper, zinc, and magnesium in hair and serum of epileptics.

The effects of long-term anticonvulsant therapy on copper (Cu), zinc (Zn), and magnesium (Mg) in the serum and hair were investigated in epileptics. Hair concentrations of Cu in both male and female epileptics, Zn in male epileptics, and Mg in female epileptics were significantly decreased when compared with those of age-matched and gender-matched controls. Hair Cu concentrations were significantly decreased in male epileptics; a significant decrease in hair Mg concentration was observed in female epileptics when compared with schizophrenics. An increased serum Cu concentration was found in female epileptics and a decreased Zn concentration was found in male epileptics. These findings suggest that long-term anticonvulsant therapy could induce alterations in both the metabolism and distribution of Cu, Zn, and Mg.

Adult

Molecular cloning of genomic DNA and chromosomal assignment of the gene for human aromatic L-amino acid decarboxylase, the enzyme for catecholamine and serotonin biosynthesis.

Aromatic L-amino acid decarboxylase (AADC) catalyzes the decarboxylation of both L-3,4-dihydroxyphenylalanine and L-5-hydroxytryptophan to dopamine and serotonin, respectively, which are major mammalian neurotransmitters and hormones belonging to catecholamines and indoleamines. This report describes the organization of the human AADC gene. We proved that the gene of human AADC consists of 15 exons spanning more than 85 kilobases and exists as a single copy in the haploid genome. The boundaries between exon and intron followed the AG/GT rule. The sizes of exons and introns ranged from 20 to 400 bp and from 1.0 to 17.7 kb, respectively, while the sizes of four introns were not determined. Untranslated regions located in the 5' region of mRNA were encoded by two exons, exons 1 and 2. The transcriptional starting point was determined around G at position -111 by primer extension and S1 mapping. There were no typical "TATA box" and "CAAT box" within 540 bp from the transcriptional starting point. The human AADC gene was mapped to chromosome band 7p12.1-p12.3 by fluorescence in situ hybridization. This is the first report on the genomic structure and chromosomal localization of the AADC gene in mammals.

Amino Acid Sequence

[A case report of serous cystadenoma located in pancreatic tail].

Cystadenomas of the pancreas are relatively rare compared to pseudocysts. There are two types of cystadenoma of the pancreas; mucinous and serous. Serous cystadenomas of the pancreas are very rare. We experienced a serous cystadenoma located in pancreatic tail. The patient was male, forty-one years old, and was free from any subjective symptom. The pancreatic cyst was found by abdominal ultrasonography and was difficult to differentiate serous or mucinous by computed tomography or celiac angiography preoperatively. We performed distal pancreatectomy and the cyst was revealed to be serous cystadenoma pathologically.

Adult

Immunogenic properties of mannose-containing ceramide disaccharide and immunochemical detection of its hapten in the two kinds of crustacean, Euphausia superba and Macrobrachium nipponense.

Antiserum against Man beta 1-4Glc beta 1-1Ceramide (MIOse2Cer), a mannolipid isolated from spermatozoa of the fresh-water bivalve, Hyriopsis schlegellii, has been elicited in rabbits by repeated injection of a mixture of hapten-bovine serum albumin (1:1, mg/ml) with Freund's adjuvant. The specificity of the affinity-purified antibody (immunoglobulin G type) obtained from the serum was examined, using other glycosphingolipids and glyco-proteins structurally related to MIOse2Cer, by means of ELISA and TLC-immunostaining. The purified antibody was highly specific to MIOse2Cer and lacked reactivity with other glycolipids and glycoproteins including glucosylceramide, lactosylceramide, dimannosylglucosylceramide (MIOse3Cer), glucosaminylmannosylglucosylceramide (ArOse3Cer), thyroglobulin and alpha 1-acid glycoprotein. The antibody was found to bind, although less efficiently, to certain other compounds containing the group Man beta 1-4Glc and/or Man beta 1-4GlcNAc at their termini, such as MIOse2-sphingosine and Man beta 1-4GlcNAc beta 1-p-aminobenzoic acid ethylester derivatives. The present antibody was applied to the detection of the natural hapten in crustacean glycolipids. The purified antibody reacted with a neutral glycosphingolipid present in the two kinds of crustacean, Euphausia superba (antarctic krill) and Macrobrachium nipponense (fresh-water shrimp) as shown by TLC-immunostaining. The crustacean glycolipid antigen was isolated and characterized to be the Man beta 1-4Glc-Cer. This is the first report on the presence of a mannose-containing glycosphingolipid in the crustacean.

Animals

Preventive effects of interleukin 1 beta for ACNU-induced myelosuppression in malignant brain tumors: the experimental and preliminary clinical studies.

The effect of recombinant human interleukin 1 beta (rHuIL-1 beta) on myelosuppression induced by 3-[(4-amino-2-methyl-5-pyrimidynyl)methyl]-1-(2-chloroethyl)-1-nit rosourea hydrochloride (ACNU) was studied. In in vivo study using BALB/c mice, pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single intraperitoneal (i.p.) injection had a significant preventive effect on thrombocytopenia as well as granulocytopenia induced by ACNU at an intravenous dose of 60 mg/kg. Facilitated recovery by rHuIL-1 beta administered seven days after injection of high-dose ACNU was also observed. Experimental combination immunochemotherapy with high-dose ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of high dose ACNU with rHuIL-1 beta. Seven patients with malignant brain tumors received intravenous 2.5-3 mg/kg ACNU. All patients were subcutaneously injected with 2 x 10(4)-U or more rHuIL-1 beta twice a week or daily. The mean nadir of leukocyte, granulocyte, and thrombocyte counts of the 7 patients received 2.5-3 mg/kg ACNU were significantly higher than in matched historical controls. In combination with rHuIL-1 beta, it may be possible to use chemotherapeutic agents at a relatively high dose.

Aged

Factors influencing the response and survival of patients with liver metastases from breast cancer receiving OK-432-combined adoptive immunotherapy.

The response and survival of 26 patients with liver metastases from breast cancer, who received OK-432-combined adoptive immunotherapy from 1984 to 1990, were evaluated. OK-432-combined adoptive immunotherapy was comprised sequential treatment via the hepatic artery with a streptococcal preparation, OK-432 (1-5 KE), and adoptive transfer of lymphocytes expanded in T-cell growth factor and sonicated tumor extract antigen. Seventeen (65%) patients responded to the therapy. The median survival time of all patients after treatment was 13 months (range, 2-63 months). Of the 20 prognostic factors analyzed, performance status (PS) alone was related to response (P less than 0.01). The response rate of the patients with a PS of 0-2 was 83% but only 25% in those with a PS of 3 or 4. In univariate analysis, 11 factors significantly influenced the survival: tumor response; size of primary tumor; menopausal status; PS; serum bilirubin, albumin, lactate dehydrogenase and glutamate-oxalate transaminase (aspartate aminotransferase); the extent of liver involvement; and the number and the proliferation rate of transferred lymphocytes. The MST was 22.8 months for the responders versus 2.8 months for the nonresponders (P less than 0.01). In multivariate analysis, the most important factor associated with survival was the tumor response, as well as PS, liver involvement, lactate dehydrogenase and albumin. These results suggest that OK-432-combined adoptive immunotherapy can be considered a candidate for a randomised control study and these factors should be used for stratification.

Breast Neoplasms

Rapid preparation of diagnostic probes for the fragile X syndrome by direct PCR amplification of human chromosomal DNA.

The fragile X syndrome is a common familial form of mental retardation and is associated with a rare fragile site at Xq27.3 (FRAXA). This disorder has recently been reported to correlate with length variations of restriction genomic DNA fragments which may due to the amplification of (CCG)n trinucleotide repeats located at the FRAXA locus. We described here a rapid preparation method of diagnostic DNA probes for the fragile X syndrome by direct enzymatic amplification of human chromosomal DNA. The PstI-assay, which is Southern blot analysis of DNA samples probed by PCR products, was shown to be sensitive method for diagnostic purposes to detect the size variations specific in the fragile X syndrome.

Base Sequence

Expressivity of a common fragile site, fra(3)(p14.2), in patients with cancer and other diseases.

A population survey of a common folate-sensitive fragile site, fra(3)(p14.2), has been carried out on PHA-stimulated peripheral lymphocytes of patients with cancer and other diseases, under both culture conditions of folate deprivation and aphidicolin treatment. Overall findings regarding variability of expressivity due to age and sex were very similar to those obtained in a healthy population. The expression of fra(3)(p14.2) by folate deficient condition appeared hardly influenced by such exogenous factors as tobacco smoking habit, past histories of radiotherapy and chemotherapy, while it was associated with the unfavorable prognosis of cancers. Furthermore, proportion of those with higher expression was slightly but significantly larger in both lung and breast cancer patients. These findings suggest that some factors relevant to the expression of fra(3)(p14.2) may be associated with development and progression of certain kinds of cancer.

Adolescent

Chromosome abnormalities and rare fragile sites detected in azoospermia patients.

We have examined constitutional chromosome abnormalities and fragile sites in 40 patients with azoospermia. Chromosome abnormalities were found in four cases. Three cases showed a deletion of the long arm of the Y chromosome 46,X,del(Yq) and the other case had a ring of G group chromosome 46,XY,r(G). In a rare fragile sites test, four fragile site carriers were detected and three rare autosomal fragile sites were identified; fra(8)(q24.1), fra(11)(p15.1), and fra(17)(p12). The expression of these fragile sites were induced specifically by AT-specific DNA ligands, such as distamycin A and Hoechst 33258. In addition, one patient was found to be the case of double ascertainment of fragile sites, fra(8)(q24.1) and fra(17)(p12). The overall frequency of distamycin A-inducible fragile sites in azoospermia patients appeared to be higher than those reported for Japanese healthy subjects and cancer patients. However, no significant relation among fragile sites, clinical and histological findings has been detected so far.

Chromosome Aberrations

Therapeutic and life-prolonging effect of intrapleural injection with a streptococcal preparation, OK-432, and IL2-cultured effusion lymphocytes to breast cancer patients with malignant pleural effusion.

We developed a local AIT using PEL cultured with TCGF combined with preadministration of OK-432. Twenty-six patients of breast cancer with pleural effusion have been treated with this therapy since 1983. PEL expanded and tumor cells collapsed by day 9 in culture with TCGF. Cultured PEL possessed significantly higher cytotoxic activity against autologous tumor cells than PBL cultured in the same condition (p less than 0.05), but there was no difference between their cytotoxic activities against K562. The proliferation rate of PEL obtained after intrapleural administration of OK-432 was higher than that obtained before OK-432 (p less than 0.01). Moreover, the cytotoxic activities against both autologous tumor and K562 of cultured PEL obtained after OK-432 administration was significantly (p less than 0.05) higher than those cultured PEL obtained before. Cultured PEL (1 x 10(8)-6 x 10(9)) were transferred into the pleural cavity after the intrapleural administration of OK-432 (1-5 KE). The volume of pleural effusion increased temporarily after the administration of OK-432 but significantly (p less than 0.01) decreased after AIT. Tumor cells disappeared cytologically in 22 patients at the last puncture of pleural effusion. Pleural effusion disappeared completely in 19 of 26 patients and decreased by more than 50% in volume in 6 patients. Performance status improved in 22 patients. The response rate for OK-432-combined AIT in the present study was 96%. The survival period of the patients treated by OK-432-combined AIT in this trial was significantly (p less than 0.002) prolonged compared to that of the patients receiving chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Sarcoidosis with tumorous hepatic and bone lesions mimicking disseminated malignancy: a case report.

An asymptomatic 49-year-old woman with a diffuse abnormal shadow detected on a routine chest rentogenogram was referred for evaluation. Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) revealed space-occupying lesions in the liver and spleen. Lymphadenopathy was observed in the mediastinum and abdomen on CT, and multiple lesions of low signal intensity were observed in the spine on MRI. Furthermore, the presence of multiple tumorous nodules in the liver suggesting metastatic hepatic cancer was demonstrated on laparoscopy. Biopsy of the liver tumors revealed sarcoidosis; transbronchial biopsy specimens showed identical histological features. After administration of prednisolone for one month, the space-occupying lesions in the liver, spleen and spine improved. This case of sarcoidosis exhibited hepatic tumorous nodules and space-occupying lesions in the spleen and the spine which mimicked the presence of metastatic hepatic cancer.

Diagnosis, Differential