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Biomedical subjects

R Horie

Publications and source records attributed to R Horie.

At least 19 recordsLinked to original sources

Frequent expression of the variant CD30 in human malignant myeloid and lymphoid neoplasms.

We earlier identified a variant of CD30 (CD30v) that retains only the cytoplasmic region of the authentic CD30. This variant is expressed in alveolar macrophages. CD30v can activate the nuclear factor-kappaB (NF-kappaB) as CD30, and its overexpression in HL-60 induced a differentiated phenotype. To better understand the physiological and pathological functions of CD30v, expression of this variant was examined using a multiple approach to examine 238 samples of human malignant myeloid and lymphoid neoplasms. Screening by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed expression of CD30v transcripts in 52 of 72, 7 of 11, 63 of 90, and 7 of 30 samples of acute myeloid leukemia (AML), myeloid blast crisis of myeloproliferative disorders (MBC), and lymphoproliferative disorders (LPDs) of B- and T-cell origin, respectively. CD30v expression was high in monocyte-oriented AMLs (FAB M4 and M5), B-cell chronic lymphocytic leukemia (B-CLL), and multiple myeloma (MM). Using the specific antibody HCD30C2, prepared using a peptide corresponding to the nine amino acids of the amino-terminal CD30v, expression of CD30v protein was detected in 10 of 25 and 2 of 10 AML and ALL samples, respectively. In AMLs, immunocytochemical detection of CD30v revealed the presence of loose clusters of CD30v-expressing cells dispersed amid a population of CD30v-negative blasts. Finally, the parallel expression of CD30v mRNA and protein, as evidenced by Northern and Western blotting, was confirmed in selected cases of AMLs and LPDs. A significant correlation was found between expressions of CD30v and CD30 ligand transcripts in AML and LPD (P = 0.02, odds ratio = 3.2). The association of CD30v with signal-transducing proteins, tumor necrosis factor receptor-associated factor (TRAF) 2, and TRAF5 was demonstrated by coimmunoprecipitation analysis, as was demonstrated for authentic CD30 protein. Expression of transcripts for TRAF1, TRAF2, TRAF3, and TRAF5, as demonstrated by RT-PCR, was noted in leukemic blasts that express CD30v. Collectively, frequent expression of CD30v along with TRAF proteins in human neoplastic cells of myeloid and lymphoid origin provide supportive evidence for biological and possible pathological functions of this protein in the growth and differentiation of a variety of myeloid and lymphoid cells.

Blotting, Northern↗

Primary gastric T-cell lymphomas: report of two cases and a review of the literature.

To understand more fully the clinicopathological features of primary gastric T-cell lymphomas (PGTL), we report two cases of PGTL and review the literature. The present cases were not associated with human T-cell leukemia virus type 1 (HTLV-1) and were at clinical stage IIE. In both cases, T-cell origin of the lymphoma cells was diagnosed immunohistochemically. The clinical courses of these two cases were different: one followed a very aggressive clinical course and the patient died 6 months after the diagnosis, whereas the other patient survived more than 2 years without adjuvant chemotherapy. Clinicopathological features of 23 patients with PGTL are summarized with regard to their differences from primary small intestinal T-cell lymphomas (PSITL) and by association with HTLV-1. The median age at onset of PGTL was 58 years. The gender ratio was male-dominant (M:F = 2.3:1). About two-thirds (10 of 17) of PGTL cases had evidence of HTLV-1 infection. The most common presenting symptom for PGTL was upper abdominal discomfort and/or pain (76%), whereas that in PSITL was weight loss (61%) and diarrhea (42%). Typical lesions for PGTL were large ulcerations at the corpus to antrum. Neoplastic cells had no typical morphological characteristics for PGTL including HTLV-1-associated cases. CD3+4+8- was the most frequently observed surface phenotype of PGTL cells. Laboratory findings at diagnosis were not informative. Most patients were treated by gastrectomy with or without chemotherapy. PGTL, excluding that with HTLV-1, showed better prognosis than PSITL, although PGTL with HTLV-1 had a poorer prognosis.

Adult↗

CD30: expression and function in health and disease.

CD30 was originally described as a marker of Hodgkin's and Reed-Sternberg cells in Hodgkin's lymphoma. Cloning and characterization of cDNAs encoding CD30 and its ligand (CD30L) established these proteins as members of the tumor necrosis factor receptor (TNFR) and tumor necrosis factor (TNF) superfamilies, respectively. Expression of CD30 is mostly restricted to virus-infected lymphocytes, neoplasms of lymphoid origin and a subset of activated T cells which produce Th2-type cytokines. The ligand is present on activated T cells, resting B cells, granulocytes, and the medulla of the thymus (epithelial cells and Hassal's corpuscles) as well as in various leukemia cells. The biological function of CD30 is pleiotropic but has come to be understood in the context of co-stimulatory signals. Signal transduction of CD30 utilizes signal transducers, TNFR-associated factors (TRAF1, 2, 3 and 5), which are shared by other TNFR family members. Mechanisms of signal transduction leading to diverse biological functions remain to be elucidated.

Animals↗

A novel domain in the CD30 cytoplasmic tail mediates NFkappaB activation.

About 100 amino acid residues in the C-terminal region are conserved among human, rat and murine CD30, a member of the tumor necrosis factor receptor (TNFR) superfamily, and can be separated into three subdomains with relatively higher conservation (D1, D2 and D3). Activation of NFkappaB by CD30 was shown to be mediated through interaction of TNFR-associated factor (TRAF) 1, 2 and 5 with the D2 and D3 subdomains. However, the function of the other conserved subdomain, D1, remained to be determined. Deletion of the D2 and D3 subdomains abolished interactions with TRAF2 and 5 but it did not affect NFkappaB activation. Reporter gene assays using deletion and mutant constructs of CD30 revealed that the D1 subdomain is sufficient for NFkappaB activation, without interaction with TRAF2 or 5, and that each subdomain alone can activate NFkappaB. Electrophoretic mobility shift assays revealed constitutive and CD30-induced NFkappaB activation in stable transformants of 293 cells expressing CD30 or a deletion mutant lacking D2 and D3 subdomains. Deletion of C-terminal 19 amino acid residues of the D1 subdomain abolished activation of NFkappaB. Substitution of alanine for one of the two threonine residues (amino acid position 524 and 529), one of which is a potential phosphorylation site in the D1 subdomain, also abolished the NFkappaB activation. Overexpression of the TRAF domain of TRAF2 or 5 had a dominant negative effect on the NFkappaB activation mediated by the D1 subdomain, thereby suggesting involvement of TRAF proteins in the signaling. Thus, the C-terminal 100 amino acid region of CD30 is composed of three independent functional subdomains, two of which contain binding sites for TRAF proteins. A novel domain in the cytoplasmic tail mediates NFkappaB activation, without direct interaction of TRAF2 or 5. Our observations suggest involvement of an unknown TRAF protein(s) in the signal transduction pathway of CD30.

Binding Sites↗

Evaluation of thrombopoiesis in thrombocytopenic disorders by simultaneous measurement of reticulated platelets of whole blood and serum thrombopoietin concentrations.

To evaluate thrombopoiesis in thrombocytopenic disorders, we simultaneously determined reticulated platelet counts in whole blood by FACScan flow cytometry and serum thrombopoietin (TPO) concentrations by a sensitive sandwich ELISA. The subjects were 40 healthy volunteers and 45 thrombocytopenic patients. In idiopathic thrombocytopenic purpura (ITP), the percentage of reticulated platelets was significantly elevated (5.61 +/- 2.02%: mean +/- SD) relative to normal controls (2.17 +/- 0.90%), but serum TPO concentrations (1.91 +/- 1.27 fmol/l) did not differ significantly from the normal range (1.43 +/- 0.62 fmol/l). The patients with aplastic anemia (AA) had decreased reticulated platelet counts and markedly increased serum TPO concentrations (13.65 +/- 10.64 fmol/l). In thrombocytopenic patients with liver cirrhosis (LC), the absolute number of reticulated platelets (1.65 +/- 1.11 x 10(9)/l) decreased similarly that in AA. However, serum TPO concentrations (1.38 +/- 0.50 fmol/l) did not increase in contrast to AA. Our findings suggested a possible dual mechanism of thrombocytopenia in LC; that is, thrombocytopenia in LC results from the decreased TPO production primarily in the liver adding to an increase in platelet sequestration in the spleen.

Anemia, Aplastic↗

Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation.

Signals emanated from CD30 can activate the nuclear factor kappaB (NFkappaB). The two conserved subdomains, D1 and D2, in the C-terminal cytoplasmic region of CD30 were tested for interaction with two tumor necrosis factor receptor-associated factor (TRAF) proteins with NFkappaB activating capacity, TRAF2 and TRAF5. TRAF5 is the newest member of the TRAF family that binds to lymphotoxin beta receptor and CD40. TRAF5, as well as TRAF2, interacted with the D2 subdomain of CD30 in vitro and in vivo. Deletion analysis by the yeast two-hybrid system revealed that the C-terminal 22 and 30 amino acid residues are dispensable for interaction of TRAF5 and TRAF2 with CD30, respectively. Substitution of alanine for threonine at 463 abolished the interaction with TRAF2. Overexpression of the TRAF domain of TRAF2 or TRAF5 showed a dominant negative effect on CD30-mediated NFkappaB activation. Simultaneous expression of these TRAF domains further suppressed the NFkappaB activation, suggesting an interplay of these TRAF proteins. Expression of TRAF2 and TRAF5 mRNA was demonstrated in T- and B-cell lines that express CD30. Taken together, our results indicate that TRAF2 and TRAF5 directly interact with CD30 and are involved in NFkappaB activation by CD30 signaling.

Amino Acid Sequence↗

Cloning and characterization of a cDNA for rat CD30 homolog and chromosomal assignment of the genomic gene.

CD30 is a member of the tumor necrosis factor receptor superfamily, which is expressed on some activated lymphocytes, virus-infected cells and transformed lymphocytes. To facilitate our understanding of biological functions and functional domains, we isolated rat cDNA clones encoding the rat homolog of human CD30 from a cDNA library of a rat T-cell line, TARL-2. The nucleotide sequence of the cDNA showed 73% homology with that of human CD30. The deduced rat CD30 protein consisted of 493 amino acids with an M(r) of 59 160 and contained a single transmembrane domain. It lacked the second repeat of the cysteine-rich motif in the extracellular domain found in human CD30. The amino acid sequence showed 51.8 and 61.2% identity with the cysteine-rich and the cytoplasmic domains, respectively. In the cytoplasmic domain, however, the amino acid sequence was highly conserved in about 100 residues near the C-terminus showing 77.7% identity, whereas the rest of the cytoplasmic domain showed 45.2% identity. This conservation suggests the functional importance of this region. Comparison with the recently reported mouse CD30 revealed 83.7% conservation of the amino acid sequence and a common structure of the extracellular domain which lacks the second cysteine-rich motif. Northern blots revealed a 3.4-kb mRNA in the PHA-activated spleen cells and human T-cell leukemia virus type 1 (HTLV-1)-infected rat T-cell lines, whereas smaller transcripts of 2.3 kb were found in the lung. A rabbit polyclonal antibody raised against GST-fusion protein of the cytoplasmic domain detected bands with an apparent M(r) of 80 kDa and 100- 110 kDa expressed in TARL-2 and spleen cells. Transient overexpression of rat CD30 in TARL-2 cells activated HIV LTR in a NF-kappa B site-dependent manner, indicating that CD30 signals activate NF-kappa B. The chromosomal location of the gene was identified by fluorescence in situ hybridisation at 5q36.2, and appeared to correspond to human 1p36, where human CD30 has been mapped. The identification and characterization of the rat counterpart of human CD30 will facilitate studies of the biological function of this molecule.

Amino Acid Sequence↗

A variant CD30 protein lacking extracellular and transmembrane domains is induced in HL-60 by tetradecanoylphorbol acetate and is expressed in alveolar macrophages.

We identified and cloned cDNAs for two novel CD30 mRNAs of 2.3 kb that are induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in the human myeloid leukemia cell line HL-60. These transcripts were transcribed from the intronic region just upstream of the exon coding for the transmembrane domain of the CD30 protein. The shorter cDNA had a deletion of 54 nucleotides corresponding to the 3' region of the transmembrane domain of the CD30 and which was probably caused by alternative splicing. Translation of these transcripts appeared to start from the internal methionine codon at nucleotide position 289 that corresponds to that of 1612 in the CD30 cDNA, and encode a protein of 132 amino acid residues which corresponds exactly to the C-terminal cytoplasmic domain of CD30 protein. The calculated molecular mass of this variant CD30 (CD30v) protein was 14,087. Thus, the predicted CD30v protein retains most of the cytoplasmic region, but lacks the extracellular and transmembrane domains. Northern blots detected the expression of CD30v transcripts only in the lung and the TPA-stimulated HL-60 cell line. Translation of this mRNA in vitro produced a protein of 25 kD. Immunoblotting analysis with HCD30C1, a rabbit polyclonal antibody raised against the cytoplasmic domain of CD30 protein, detected proteins with an apparent Mr 25 kD expressed in TPA-stimulated HL-60 and COS-7 cells that were transfected with both types of CD30v cDNAs. Constitutive phosphorylation of the CD30v protein was demonstrated by in vitro labeling with [32P]. Immunohistochemical studies demonstrated CD30v protein was in alveolar macrophages. Cotransfection experiments using a kappa B-site-dependent reporter construct showed that CD30v can transactivate gene expression through activation of NF kappa B, as was noted on the authentic CD30 protein. Overexpression of the CD30v induced differentiation of HL-60 cells as evidenced by an increased NBT reduction activity. These observations provided new insights into the molecular heterogeneity and biological function of CD30 in myeloid cells.

Animals↗

Alterations in gastric mucin with malignant transformation: novel pathway for mucin synthesis.

BACKGROUND: Mucins are high-molecular-weight glycoproteins produced by both normal and cancer cells. However, in cancer cells, abnormal mucins are synthesized and potentially can be used as markers for the development and progression of certain malignancies. In a previous study, we reported the production of a new monoclonal antibody directed against a mucin antigen termed F1 alpha, an O-linked oligosaccharide similar to sialyl Tn and Thomsen-Friedenreich (T) antigens, that has not been previously detected in human cancers. F1 alpha is expressed in a high percentage (80.2%; 89/111) of gastric cancers. PURPOSE: In the present study, we compared the expression of F1 alpha with that of sialyl Tn and T antigens in human gastric cancer tissues to determine how differences in the expression of these cancer-associated antigens correlated with the biological properties of cancer cells. METHODS: A total of 141 cases of gastric cancer were studied. Sections of formalin-fixed, paraffin-embedded tissue were immunostained for F1 alpha, sialyl Tn, and T antigens. The relationship between the expression of these antigens and the patient's clinicopathologic characteristics was studied. The chi-square test (two-sided) was used for statistical analyses. RESULTS: F1 alpha was expressed in a high percentage of the cases of early to advanced cancers, irrespective of the degree of malignant progression. The rate of expression of sialyl Tn antigen in early carcinoma was low, but it increased significantly as depth of invasion increased (P < .05) and was significantly higher in patients with hepatic or lymph node metastasis than in those without such metastasis (P < .01). Expression of T antigen significantly increased with depth of invasion (P < .01) and was significantly higher in patients with hepatic metastasis (P < .05), lymph node metastasis (P < .05), or peritoneal dissemination (P < .01) than in those without such metastasis or dissemination. In consecutive sections of the same specimen, the sites of staining for F1 alpha and sialyl Tn antigens seldom coincided. In many cases, F1 alpha staining was predominant, but the sialyl Tn-dominant region tended to increase as gastric cancer progressed. Regions of T-antigen staining were usually circumscribed by those of F1 alpha staining. CONCLUSION: Our findings indicate that the expression of F1 alpha begins almost at the same time as does carcinogenesis in gastric epithelial cells. Moreover, in association with progression of gastric carcinoma, synthetic pathways for sialyl Tn antigen and T antigen probably are activated independently.

Antigens, Surface↗

Synthesis of neoglycolipids containing a mucin-type core unit.

The unnatural glycolipids O-beta-D-galactopyranosyl-(1-->4)-O-(2-acetamido- 2-deoxy-beta-D-glucopyranosyl)-(1-->3)-O-(2-acetamido-2-deoxy-alpha-D- galactopyranosyl)-(1-->1)-ceramide (1), O-beta-D-galactopyranosyl-(1-->4)-O-(2-acetamido-2-deoxy-beta-D-glucopyr anosyl) - (1-->6)-O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-(1-->1)-ceramid e (2), and O-beta-D-galactopyranosyl-(1-->4)-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1-->3)-O-[O-beta-D-galactopyranosyl-(1-->4)-(2-acetamid o-2- deoxy-beta-D-glucopyranosyl)-(1-->6)]-O-(2-acetamido-2-deoxy-alpha-D- galactopyranosyl)-(1-->1)-ceramide (3), and their beta-(1-->1)-linked isomers, were synthesized. The precursor oligosaccharides for 1, 2, and 3 were made by coupling O-2,3,4,6- tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->4)-3,6-di-O-acetyl-2- deoxy-2-phthalimido-alpha,beta-D-glucopyranosyl trichloroacetimidate with tert-butyldiphenylsilyl 2-azido-4,6-O-benzylidene-2-deoxy-beta-D-galactopyranoside, tert-butyldiphenylsilyl 2-azido-3-O-benzoyl-2-deoxy-beta-D-galactopyranoside, and tert-butyl-diphenylsilyl O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->4)-O-(3,6-di-O-a cetyl-2 - deoxy-2-phthalimido-beta-D-glucopyranosyl)-(1-->3)-2-azido-2-deoxy-beta- D- galactopyranoside, respectively. These oligosaccharides were converted into their trichloroacetimidates, which were coupled with 3,2'-di-O-benzoyl ceramide. Deprotection of the coupling products gave the title compounds 1, 2, and 3.

Carbohydrate Conformation↗

A new cancer-associated antigen defined by a monoclonal antibody against a synthetic carbohydrate chain.

Carbohydrate antigens can be designed by referring to previously defined carbohydrate structures. We have generated a novel monoclonal antibody (MAb) (F1 alpha-75) against an artificially designed antigen (F1 alpha), using organic-synthetic chemistry methods and hybridoma technology. F1 alpha (Gal beta 1-->4GlcNAc beta 1-->6GalNAc alpha 1-->Ser/Thr) belongs to core type 6 of O-linked glycans, which has not been previously reported in human cancers. To produce antibodies against F1 alpha, a glycolipid was synthesized which carries the carbohydrate portion of F1 alpha on a ceramide foundation (Gal beta 1-->4GlcNAc beta 1-->6GalNAc alpha 1-->Cer). The MAbs we obtained (F1 alpha-75, F1 alpha-87) specifically recognized F1 alpha and had only a very weak or no cross-reactivity with other glycolipids similar to F1 alpha. We investigated the expression of F1 alpha in human tissues, including 110 gastric cancers, 73 colon cancers and 42 pancreatic cancers. F1 alpha was found in human cancerous tissues but not in normal adult tissues. The rate of positive staining with F1 alpha-75 was 80.0% for gastric cancer, 52.4% for pancreatic cancer and 38.4% for colon cancer. F1 alpha-75 also reacted with the tissues neighboring gastric and pancreatic tumors but not intensely. Among fetal tissues, F1 alpha-75 reacted with the pyloric glands of the stomach, the centro-acinar cells of the pancreas, the convoluted tubules of the kidney and the terminal bronchioles of the lung.

Antibodies, Monoclonal↗

Community-based prevention of stroke: nutritional improvement in Japan.

OBJECTIVES: (1) To demonstrate the importance of nutrition, especially sodium restriction and increased potassium and protein intakes, in the prevention of hypertension and stroke in a pilot study involving senior citizens. (2) To design a population-based intervention in the Shimane Prefecture of Japan concerning dietary factors such as low sodium and high potassium, protein, magnesium, calcium and dietary fibre in the prevention of stroke. DESIGN AND METHODS: The intervention study was carried out at a senior citizens' residence and included general health education along with a reduction of dietary salt intake and increases in vegetable and protein, especially from seafood. Sixty-three healthy senior citizens (average age: 74.8 +/- 7.7 years) had their daily meals modified to a low sodium/potassium ratio for four weeks without their knowledge by the use of a potassium chloride substitute for salt, soy sauce and bean paste, which contains much less sodium and more potassium. Monosodium L-glutamate monohydrate used for cooking was changed to monopotassium L-glutamate monohydrate. Blood pressure was measured with the patient in the sitting position. Daily dietary sodium and potassium intakes were assessed by flame photometry from 24-hour urine specimens. Extensive intervention programs were introduced into the Shimane Prefecture, which has a population of 750,000, through health education classes for housewives, home visits by health nurses and an educational TV program for dietary improvement. The mortality from stroke was monitored for 10 years and compared with the average in Japan. RESULTS: The blood pressure lowering effect of reducing the dietary sodium/potassium ratio was confirmed through a pilot intervention study at the senior citizens' residence. The mortality rates for stroke in the middle-aged population from the Shimane Prefecture during the 10 years after the introduction of dietary improvement had a steeper decline in hemorrhagic, ischemic and all strokes than the average for Japan.

Adult↗

Nutritional factors for stroke and major cardiovascular diseases: international epidemiological comparison of dietary prevention.

OBJECTIVE: To assess the relationship of biological markers of dietary factors with blood pressure (BP) (Core Study) and with age-adjusted mortality rates of stroke and ischemic heart disease (Complete Study) in the WHO Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study, a multicentre epidemiological study in 55 centres of 24 countries as of 1993. DESIGN AND METHODS: From each population, 100 men and 100 women aged 48 to 56 years were randomly selected for BP measurement, 24-hour urine collection, blood tests, etc. Various biological dietary markers from the urine and blood were analysed centrally. Age-adjusted mortality rates from stroke and ischemic heart disease were obtained from 19 centres in 14 countries. RESULTS: Core Study: Cross-centre analyses, using simple linear regression, showed a positive relationship of body mass index to systolic BP and diastolic BP in men (p < 0.001) and women (p < 0.05). There were also strong positive correlations between 24-hour sodium excretion rates and both systolic and diastolic BP (both p < 0.01) in men. An inverse relationship was found between the 24-hour magnesium/creatinine excretion ratio and diastolic BP (p < 0.05) in men. Complete Study: Stroke mortality was significantly positively related to the 24-hour sodium excretion rate in men (p < 0.01) and to the sodium/potassium ratio in both sexes (p < 0.05). It showed an inverse relationship of serum phospholipid with serum total cholesterol (p < 0.05) and a positive relationship with arachidonic acid. A strong positive relationship between serum cholesterol level and ischemic heart disease (p < 0.001) was observed in men. The serum phospholipid n-3 polyunsaturated fatty acid (PUFA) level and the PUFA to saturated fatty acid (SFA) ratio were significantly inversely correlated with ischemic heart disease. The 24-hour taurine excretion rate, a biological marker of seafood protein intake, showed a significant inverse correlation with ischemic heart disease in both sexes (p < 0.01). CONCLUSION: The Core Study revealed a consistent adverse effect of high body mass index and excess salt intake on BP and a beneficial effect of magnesium on BP. The Complete Study demonstrated an adverse effect of high sodium, low potassium intake and hypercholesterolemia on stroke; and an adverse effect of cholesterolemia as well as beneficial effects of serum phospholipid n-3 PUFA, PUFA/SFA and the taurine excretion rate on death from ischemic heart disease.

Arachidonic Acids↗

High expression of the CD30 molecule in human decidual cells.

CD30 is a receptor-type membrane protein that belongs to the nerve growth receptor superfamily. It is expressed on Hodgkin's cells and activated lymphocytes, as well as in some human malignancies including malignant lymphomas, embryonal carcinomas, and other mesenchymal tumors. However, whether it is expressed in normal tissues remains unclear. To study the expression and biological function of CD30, we first examined various human tissues by immunohistochemistry. The monoclonal antibody Ber-H2 intensely stained the membranes of decidual and endometrial cells with decidual change in frozen sections. Western blots of these tissues with Ber-H2 revealed bands of 120, 105, and 90 kd as found on CD30-expressing cells. Northern blots of these tissues using a CD30 cDNA probe detected mRNAs of the same molecular mass and variety as those in the positive control cell line HUT 102. These results indicated that CD30 is expressed in human endometrial tissue with decidual change and imply that CD30 expression in endometrial tissue is induced by hormonal control.

Base Sequence↗

Cerebrovascular protection by sequential bilateral carotid artery ligation in aged spontaneously hypertensive rats.

1. Sequential bilateral carotid artery ligation (BCL) separated by a 1 week interval was performed on 5 month spontaneously hypertensive rats (SHR) (i.e. SHRSR-B1/Izm) and the developmental course of hypertension and cerebrovascular lesions in advanced age were analysed as compared with those in age-matched sham-operated controls. 2. Behavioural activity and behavioural reaction to light were also investigated in the above-mentioned SHR, young and adult stroke-prone SHR (i.e. SHRSP-A3/Izm), SHR (i.e. B1/Izm) and Wistar-Kyoto rats (i.e. WKY/Izm). 3. All of the control SHR developed severe hypertension resulting in cerebral stroke with focal oedema due to cerebral haemorrhage and infarction as a result of arterionecrosis 18 months after birth. 4. SHR usually die within a few days of BCL. In the present study, however, they successfully survived without cerebrovascular damage for a long time, although they developed a similar severe hypertension in a significantly shorter period of time (P < 0.05) and showed behavioural abnormalities that were probably due to severe cerebral ischaemia. 5. These experimental results suggest an ischaemic tolerance phenomenon in a hypertensive model that was exposed to mild ischaemic stress by unilateral carotid artery ligation (UCL) before the subsequent induction of severe ischaemia by BCL. The results also suggest that an aggravation of hypertensive cerebrovascular changes due to long-lasting ischaemia after BCL was prevented through a possible cumulative effect of ischaemic stress.

Aging↗

Intralymphocytic free calcium and magnesium in stroke-prone spontaneously hypertensive rats and effects of blood pressure and various antihypertensive agents.

1. Free Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were measured in peripheral lymphocytes from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) at the age of 5, 7 and 17 weeks, from various antihypertensive agents-treated SHRSP, and from secondary hypertensive WKY. 2. At the age of 5 weeks, no difference was observed in systolic blood pressure (SBP), or lymphocyte [Ca2+]i and [Mg2+]i between SHRSP and WKY. At the age of 7 or 17 weeks, SBP and [Ca2+]i of SHRSP were significantly higher than in WKY, and at the age of 17 weeks, [Mg2+]i of SHRSP was significantly lower than in WKY. Further, [Ca2+]i or [Mg2+]i was positively or negatively correlated to SBP, and [Mg2+]i was negatively correlated to [Ca2+]i. 3. SBP of SHRSP fell significantly after antihypertensive treatment with calcium antagonist, angiotensin-converting enzyme (ACE) inhibitor or hydralazine for 40 days. [Ca2+]i was significantly lower in calcium antagonist and hydralazine groups, and tended to be low in ACE inhibitor group. These four groups showed no difference in [Mg2+]i. 4. After 40-day administration of NG-nitro-L-arginine (L-NNA), WKY developed severe hypertension, but there were no significant differences in lymphocyte [Ca2+]i and [Mg2+]i between the L-NNA treated and non-treated groups. 5. These results suggested that increased lymphocyte [Ca2+]i and decreased [Mg2+]i observed in SHRSP are not only secondary to hypertension but possibly related to a basic genetic abnormality of divalent cation handling.

Animals↗