Superconductivity in 5d transition metal Laves phase SrIr2.

We report here the superconducting properties of a Laves phase superconductor SrIr2, which has a cubic MgCu2 structure. SrIr2 is a type-II superconductor, with a T c of 5.9 K. The estimated superconducting parameters of lower critical field µ 0 H c1 and upper critical field µ 0 H c2, coherence length ξ(0), penetration depth λ(0) and Ginzburg-Landau (GL) parameter κ(0) are approximately µ 0 H c1 = 101 Oe, µ 0 H c2(0) = 5.9 T, ξ(0) = 7.47 nm, λ(0) = 237 nm, and κ(0) = 31.7, respectively. The specific-heat data indicate that SrIr2 is a strong-coupling superconductor because the value of ΔC/γT c is approximately 1.71, which is larger than the value of 1.43 that is expected from the BCS theory. The physical properties obtained in this study are explained well by theoretical calculations including spin-orbit coupling (SOC). This result indicates that the physical properties of SrIr2 are strongly affected by the presence of SOC.

DHMEQ, a new NF-kappaB inhibitor, induces apoptosis and enhances fludarabine effects on chronic lymphocytic leukemia cells.

Chronic lymphocytic leukemia (CLL) is a low-grade lymphoid malignancy incurable with conventional modalities of chemotherapy. Strong and constitutive nuclear factor kappa B (NF-kappaB) activation is a characteristic of CLL cells. We examined the effects of a new NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on CLL cells. Dehydroxymethylepoxyquinomicin completely abrogated constitutive NF-kappaB activity and induced apoptosis of CLL cells. Apoptosis induced by DHMEQ was accompanied by downregulation of NF-kappaB-dependent antiapoptotic genes: c-IAP, Bfl-1, Bcl-X(L) and c-FLIP. Dehydroxymethylepoxyquinomicin also inhibited NF-kappaB induced by CD40 and enhanced fludarabine-mediated apoptosis of CLL cells. Results of this study suggest that inhibition of constitutive and inducible NF-kappaB by DHMEQ in combination with fludarabine is a promising strategy for the treatment of CLL.

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.

Dietary effect on platelet aggregation in men with and without a family history of essential hypertension.

Platelet aggregation induced by 5 microM adenosine 5'-diphosphate (ADP) was significantly higher in men with a family history of essential hypertension than in men without such a history when they were fed a low fat-cholesterol diet with low salt. Platelet aggregation activity was remarkably increased in both groups when the diet was changed from low salt into high salt. Platelet aggregation activity was higher in the group with a positive family history of hypertension on the low fat-cholesterol plus high salt diet than in the group without a family history under the same conditions. The activity was slightly increased in both groups when fed a high fat-cholesterol diet with low salt. There was no significant difference in the platelet aggregation between the two groups. The activity was significantly increased in both groups on the high fat-cholesterol diet after the diet was changed from low salt to high salt. Under both the low and high fat-cholesterol diets, the mean blood pressure was significantly elevated in response to excessive salt intake in the group with a family history of essential hypertension, but it was not elevated in the group without such a family history.

Humoral trophic influence on cardiovascular structural changes in hypertension.

Since the early development of structural cardiovascular change in spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) indicated the involvement of non-pressure-dependent factors in this process in hypertension, smooth muscle cells (SMC) from the aorta of SHR, SHRSP, and normotensive Wistar-Kyoto rats (WKY) were investigated under tissue culture conditions free from blood pressure and humoral factors in vivo. By the observation of such factors as growth rate and DNA or protein synthesis vascular SMC from these rats with genetic hypertension were proved to have intrinsically greater growth activity independently of blood pressure. Although serum from SHR and SHRSP had no specific stimulative effect on SMC growth, circulating epinephrine may accelerate cardiovascular structural changes because isoproterenol added to the culture media enhanced ornithine decarboxylase (ODC) activity. Moreover, SMC from SHR and SHRSP showed greater thymidine incorporation than those from WKY even in response to lower extracellular Na+ concentration. Local nutritional conditions of SMC, which were proved to have a great effect on the morphology and structure of cultured SMC, may be a basic determinant of the development of hypertension-induced structural vascular changes or lesions.

Possible role of nutritional factors in the incidence of cerebral lesions in stroke-prone spontaneously hypertensive rats.

The incidence of cerebral lesions in stroke-prone spontaneously hypertensive rats appears to depend on the severity of the hypertension and nutritional factors. Comparison of American and Japanese commercial rat diets revealed a much higher incidence of stroke in rats receiving the Japanese diet (88% vs 30% by 9 months of age). Analyses of the diets indicate that perhaps the most important difference in the two diets is the protein content. Based on complete amino acid analyses of the protein in these diets, it appears that the American diet contains about 22% protein as compared to about 15% for the Japanese diet. Minor differences in vitamin and mineral contents are not remarkable. Comparison of the findings in this experimental rat model with epidemiologic studies suggest that nutritional factors may also play a role in the incidence of stroke in humans.

Interrelationships between blood pressure, sodium, potassium, serum cholesterol, and protein intake in Japanese.

Interrelationships among blood pressure (BP), sodium (Na), potassium (K), dietary protein, and serum cholesterol level (Chol) were examined in 62% (1120) of 1818 Japanese inhabitants of both sexes aged over 30 years who lived in a rural village in Japan. Fasting single-spot urine specimens were collected in the morning to measure Na, K, urea nitrogen (UN), inorganic sulfate (SO4), and creatinine (Cr). The Cr ratios of Na, K, UN, SO4, Na/K, and SO4/UN were analyzed by multiple regression analysis to determine independent associations with BP together with age, obesity index, hematocrit (Hct), Chol, triglyceride (TG), and fasting serum glucose level (Glu). Except for Na/Cr in men, Na/Cr and Na/K were found to be independently and positively related to BP, particularly to systolic BP (SBP). In contrast, K/Cr and SO4/UN (an index related to the dietary score of sulphur-containing amino acids derived mainly from animal protein) were both negatively associated with SBP, and UN/Cr (an index of total protein intake) was positively associated with SBP in men. Chol was linked to BP negatively in men but positively in women. Age, obesity index, TG, and Hct were generally positively and significantly related to BP in both sexes. The results confirmed on epidemiological grounds the positive link of Na and the negative link of K to BP within a single population in Japan. They further suggest, although only in men, that there is a negative relationship of Chol and dietary animal protein with BP.

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.

Effects of low-dose chronic diltiazem treatment on hemodynamic changes in spontaneously hypertensive rats.

The effects of long-term diltiazem treatment on hemodynamic and cardiovascular characteristics were investigated in young spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY) and their respective untreated controls. The drug was administered to treated rats over a period of 24 weeks. Body weight, left ventricular weight, mean arterial pressure (MAP), heart rate, max dp/dt or maximum velocity of the contractile element (Vmax) were not significantly different in diltiazem-treated SHR and untreated SHR. In diltiazem-treated SHR, cardiac index (CI) and stroke volume index (SI) were significantly increased and total peripheral resistance and the index of left ventricular compliance (delta P/delta V) were significantly decreased compared with untreated SHR. Left ventricular pumping ability in treated SHR was higher than that in untreated SHR, despite the low dose of diltiazem given. However, there was no significant difference between treated and untreated WKY. Long-term diltiazem treatment did not affect left ventricular function or biochemical properties in SHR and WKY. These data suggest that long-term diltiazem treatment improves pump function in SHR without changing blood pressure.

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.

Cardiac hypertrophy in early hypertension.

Studies of cardiac hypertrophy in spontaneously hypertensive rats have indicated that left ventricular hypertrophy occurred even in the prehypertensive stage. These findings suggested that other factors besides blood pressure levels, and including possibly a genetic predisposition to myocardial hypertrophy, could play a role in structural cardiovascular alterations in spontaneously hypertensive rats. More recent studies have confirmed these anatomic results; left ventricular hypertrophy was vectorcardiographically detected even in the prehypertensive stage in voth young stroke-prone rats and stroke-resistant spontaneously hypertensive rats. Further, a close relation was found between degree of left ventricular hypertrophy and vascular hypertrophy or hyperplasia; this suggests that early detection of left ventricular hypertrophy may be a useful indicator of the incipient stage of structural vascular changes in genetic hypertension.

White matter lesions and alteration of vascular cell composition in the brain of spontaneously hypertensive rats.

There have been few studies on the white matter lesions of spontaneously hypertensive rats (SHR). From the point of view of hypertension and arteriosclerosis, white matter lesions were examined in SHR and stroke-prone SHR (SHRSP), and were then compared with Wistar-Kyoto (WKY) rats. The vasculopathy was analyzed by morphometric immunohistochemistry for collagen and smooth muscle actin. Both SHR and SHRSP had hypertension at > or = 12 weeks of age, and the latter developed severe white matter lesions at 20 weeks. Immuno- histochemistry revealed proliferation of microglia in the white matter and an increase in smooth muscle actin in the vessels of SHRSP compared with the WKY rats and SHR, but there were no changes in the collagen. These results indicate a role of hypertension in the pathogenesis of white matter lesions. However, genetic difference may also be responsible since SHR and SHRSP showed similar hypertension.

The hypotensive effect of centrally administered tyrosine.

Intraventricular injection of 15 microgram L-tyrosine results in a significant reduction in blood pressure in the spontaneously hypertensive rat. An increase in the turnover of norepinephrine as indexed by MOPEG-SO4 is observed concurrently. The data are consistent with the previously suggested depressor role of certain central noradrenergic neurons.

Effect of unilateral carotid ligation on brainstem PNMT activity.

Phenylethanolamine N-methyltransferase (PNMT) activity in the C1 and C2 regions of the brainstem was assayed in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with or without unilateral carotid artery ligation. PNMT activity was significantly higher in SHR than in WKY (P less than 0.01). PNMT activity in the C1 and C2 regions on non-ligated side in both WKY and SHR was significantly elevated compared with that on the ligated side. These results indicate that the activity of PNMT in adrenergic neurons may respond to baroreflex activation and that adrenergic neurons may be involved in blood pressure regulation.

Molecular cloning and sequencing of myosin light chains in human megakaryoblastic leukemia cells.

Myosin light chain genes of hematopoietic cells have yet to be characterized. We cloned the full-length cDNAs of 20 kDa regulatory myosin light chain (MLC-2) and 17 kDa essential myosin light chain (MLC-3) from Meg-01, a human megakaryoblastic leukemia cell line. Both MLC-2 and MLC-3 gene are transcribed ubiquitously in various hematopoietic cells. The MLC-2 open reading frame of 516 nucleotides encoding a protein of 172 residues was detected in cloned cDNA of 967 nucleotides. The Ca2+-binding domain and five phosphorylation sites were highly conserved. The deduced amino acid sequence has a 99.4% and 100% homology with that of human fetus brain and human lymphocyte, respectively. The MLC-3 open reading frame of 453 nucleotides encoding a protein of 151 residues was detected in cloned cDNA of 742 nucleotide. The MLC-3 protein is 99.3% identical to that of human fibroblasts. These results suggest that hematopoietic myosin light chain proteins are similar to those of other nonmuscle cells and smooth muscle, thus differing from skeletal and cardiac muscles.

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.

Effect of milk protein and fat intake on blood pressure and the incidence of cerebrovascular diseases in stroke-prone spontaneously hypertensive rats (SHRSP).

The intake of two milk protein-rich diets containing casein and whey protein attenuated the development of severe hypertension in stroke-prone spontaneously hypertensive rats (SHRSP), and extended their life span in comparison with SHRSP on a regular stock diet. Milk fat-rich diet intake reduced the incidence of cerebrovascular disease in SHRSP without a significant fall in blood pressure. These results suggest that certain milk components have a preventive effect on hypertension and cerebrovascular disease in SHRSP.

International cooperative study on the relationship between dietary factors and blood pressure: a preliminary report from the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The CARDIAC Cooperative Study Research Group.

1. To investigate the epidemiological relationship of dietary factors to blood pressure (BP) and major cardiovascular diseases, we carried out the international cooperative Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study, which so far involves 48 centers in 20 countries as of August 1991. From each population, 100 men and 100 women aged 50-54 years were randomly selected for BP measurement, 24-h urine collection, blood tests, and medical interview. Various biological markers of diets from urine and blood were analyzed centrally in the Izumo CARDIAC center. 2. Cross center analysis using simple linear regression revealed strong significant correlations of body mass index (BMI) to systolic BP (SBP; p < 0.01) and diastolic BP (DBP; p < 0.001) in men. 24-h urinary sodium (Na) excretion in men also showed significant correlations with SBP (p < 0.05) and DBP p < 0.05) even after controlling for the effect of BMI (SBP; p < 0.05, DBP; p < 0.05). 3. Within center analysis using multiple linear regression implied that BMI and Na strongly adversely affect BP, whereas magnesium may have beneficial influence on BP. 4. Multicolinearities among 24h urinary sodium, calcium, and urea nitrogen were noted in men.

[Role of ultrasonography in diagnosis of neutropenic enteritis: a study of 4 cases].

Neutropenic enteritis is a septic or inflammatory disease of the colon. It is usually encountered in patients with hematological malignancy who have undergone chemotherapy, and it presents as fever, diarrhea, and abdominal pain, although the symptoms are not always specific. The diagnostic features of neutropenic enteritis revealed by barium enema, CT and ultrasonography have been reported previously. Here we report 4 cases of neutropenic enteritis in which ultrasound was used for diagnosis, and also for monitoring the clinical course of the disease. Because neutropenic enteritis is rapidly progressive, early diagnosis and therapeutic intervention are required. We believe that ultrasonography is a useful method for examining patients with neutropenic enteritis, being noninvasive, mobile, and providing rapid results in real time, thus aiding early diagnosis and clinical follow-up.

[Acute leukemia successfully treated with natural interferon-alpha].

Natural interferon-alpha (IFN-alpha) alone was administered to a 42-year-old man with acute leukemia, whose bone marrow revealed hypocellularity (NCC = 6 X 10(4)/microliters) and a 50% increase in blasts. Initial chemotherapy regimens, including BHAC-DMP or low dose Ara-C were ineffective. One month after starting nIFN-alpha therapy, the blasts in his bone marrow decreased below 3% and peripheral blood cell counts became normal. He has been in remission for at least 7 months.