Stretching cardiac myocytes stimulates protooncogene expression.

Recently cellular protooncogenes have been found to be induced as an early response to pressure overload in cardiac hypertrophy. To examine whether mechanical stimuli directly induce specific gene expression in the heart, we cultured rat neonatal cardiocytes in elastic silicone dishes and stretched these adherent cells. Myocyte stretching stimulated expression of the protooncogene, c-fos, in a stretch length-dependent manner, followed by an increase in amino acid incorporation into proteins.

Regulatory mechanisms of erythropoietin levels in dialysis patients.

We described a radioimmunoassay system for measuring blood erythropoietin (Epo) levels using recombinant human Epo and evaluated the regulatory mechanisms of Epo in dialysis patients. A satisfactory dose-response relationship for Epo levels was observed within the wide range of 3-250 mU/ml with a sensitivity of approximately 5 mU/ml. The Epo levels were found to be 16.

Overexpression confers an oncogenic potential upon the eph gene.

The eph gene encodes a putative receptor tyrosine kinase for an as yet unknown ligand. Some human cancer cells have been found to overexpress eph mRNAs without gene amplification. We show here that NIH3T3 cells acquire tumorigenic ability in nude mice and make colonies in soft agar with a viral LTR (Long Terminal Repeat)-driven artificial expression of the eph gene to a high level.

Recombinant human erythropoietin corrects anemia of blood loss: a study in the dog.

In order to evaluate the possibility of using recombinant human erythropoietin (rhEpo) for the prevention and correction of anemia due to blood loss and as an adjuvant for autologous blood transfusion, its preventive and therapeutic effects were evaluated in beagles in which anemia was induced by repeated phlebotomies. Two hundred U/kg of rhEpo were administered i.v.

Spontaneous release of angiotensin converting enzyme and interleukin 1 beta from peripheral blood monocytes from patients with rheumatoid arthritis under a serum free condition.

Angiotensin converting enzyme (ACE) and interleukin 1 activities were assayed simultaneously in the serum free medium from the unstimulated peripheral blood monocytes from 32 patients with rheumatoid arthritis (RA), 11 patients with osteoarthritis, and 25 normal controls matched for age and sex. Angiotensin converting enzyme activity was raised in most (29/32) patients with RA and interleukin 1 activity (most of which was interleukin 1 beta) was enhanced in 11/32 patients with RA, while monocytes from only two patients with osteoarthritis, but from none of the controls, secreted a small amount of ACE alone in the culture condition. Monocytes from patients with early RA (disease duration less than 3 years) released significantly more ACE and interleukin 1 than those from late stage RA (disease duration greater than or equal to 3 years).

[Two cases of advanced gastric cancer with diffuse carcinomatosis of the bone marrow showing a widespread osteoplastic bone metastasis].

Reported are 2 cases of an advanced gastric cancer with a "diffuse carcinomatosis of the bone marrow" (DCMB) showing a widespread osteoplastic bone metastasis. In a DCBM, a widespread invasion of cancer cells to the bone marrow occurs, causing leukoerythroblastosis, anemia, and disseminated intravascular coagulation. The local reaction in the bone, namely being osteoplastic or osteolytic, has not been discussed in previous papers.

Identification and cellular distribution of distinct proteins forming human GM-CSF receptor.

Two proteins forming the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF)1 were identified and characterized. One with apparent Mr of about 80,000 was defined as alpha-chain and has Kd of 0.7-2.

[A phase III study of KRN 8601 (rhG-CSF) on neutropenia induced by chemotherapy for malignant lymphoma--a multi-institutional placebo controlled double-blind comparative study].

The clinical usefulness of KRN 8601 (rhG-CSF) was evaluated in patients with neutropenia induced by chemotherapy for non-Hodgkin lymphoma in a double-blind study. The same chemotherapeutic regimens repeated for twice in 3 to 4 weeks interval. During the first cycle of chemotherapy, changes of leukopenia (neutropenia) were observed, and KRN 8601 at a dose of 75 micrograms/body or placebo was started to administer subcutaneously 72 hours after the termination of the second cycle and continued for 14 days.

Latent form of transforming growth factor-beta 1 acts as a potent growth inhibitor on a human erythroleukemia cell line.

Recombinant latent form of transforming growth factor-beta 1 (L-TGF-beta 1) is activated by various chemical treatments, including acidification and heating. However, cellular mechanisms that release transforming growth factor-beta (TGF-beta) in an active form have not been fully elucidated. Investigated herein are the effects of L-TGF-beta 1 on various leukemic cell lines.

Apolipoprotein E and lipoprotein lipase secreted from human monocyte-derived macrophages modulate very low density lipoprotein uptake.

We investigated the roles of lipoprotein lipase and apolipoprotein E (apoE) secreted from human monocyte-derived macrophages in the uptake of very low density lipoproteins (VLDL). ApoCII-deficient VLDL were isolated from a patient with apoCII deficiency. The lipolytic conversion to higher density and the degradation of the apoCII-deficient VLDL by macrophages were very slight, whereas the addition of apoCII enhanced both their conversion and degradation.

Susceptibility of human erythropoietic cells to B19 parvovirus in vitro increases with differentiation.

B19 human parvovirus is the etiologic agent of transient aplastic crisis. To better understand B19 virus-induced hematopoietic suppression, we studied the host cell range of the virus using in vitro bone marrow cultures. First, B19 virus replication was examined in the presence of various purified cytokines using DNA dot blot analysis.

Changes in thyroglobulin release-stimulating activity (Tg-RSA) in immunoglobulin G from patients with Graves' disease during therapy with thionamide drug.

We have reported previously a new method for detecting thyroglobulin release stimulating activity (Tg-RSA) by human thyroid monolayer cells in IgGs from Graves' patients. We report here changes in Tg-RSA in sera of patients during treatment with thionamide drug. Nineteen untreated patients had their Tg-RSA, TSAb, TBII and serum Tg concentration (STg) followed up.

Interleukin 1 increases the production of endothelin-1 by cultured endothelial cells.

We examined the effect of human recombinant interleukin 1 (IL-1) on the production of endothelin-1 by cultured porcine endothelial cells. The induction of endothelin-1 mRNA began within 1 hr of exposure to IL-1, showed twin peaks at 4 and 24 hr, and declined thereafter. Enzyme-linked immunosorbent assay revealed that the amount of endothelin-1 peptide in conditioned media was also increased by IL-1 in a dose- and time-dependent manner.

Effect of exogenous apo E on the cellular binding of lipoproteins.

It is well known that apolipoprotein E (apo E) has a significant role in the metabolism of plasma cholesterol through receptor-mediated endocytosis of lipoproteins containing apo B 100. We have reported that intravenous administration of apo E increases the clearance of lipoproteins containing apo B 100, resulting in reduced plasma cholesterol levels in WHHL rabbits. In the present study, we investigated the effects of exogenous apo E on lipoprotein binding to cell surface receptors.

Human ltk: gene structure and preferential expression in human leukemic cells.

We have isolated the human homolog (hltk) of the murine tyrosine kinase gene ltk from a K-562 human leukemia cDNA library. The deduced protein sequence of hltk is 17 amino acids longer in the juxtamembrane domain and 28 amino acids shorter in the carboxy terminus than that of murine ltk. The partially identical splicing points of hltk to those of c-ros showed a close genetic linkage between the two.

Pirarubicin, a novel derivative of doxorubicin. THP-COP therapy for non-Hodgkin's lymphoma in the elderly.

Pirarubicin (tetrahydropyranyl adriamycin, THP) is a derivative of doxorubicin. Forty-three non-Hodgkin's lymphoma (NHL) patients 65 years of age or older were treated with a combination therapy including cyclophosphamide (CPA), vincristine (VCR), prednisone (PSL), and THP (THP-COP). The THP-COP regimen consisted of THP, 30 mg/m2 i.

Glycosphingolipid composition of the gastric mucosa. A role of sulfatides in gastrointestinal mucosal defense?

The glycosphingolipid (GSL) compositions of the human, rabbit, and rat gastric mucosa were studied and compared. In neutral GSLs, although GalCer was the most abundant component in every tissue examined, species-specific differences were clearly observed in their composition. Acidic GSLs were composed of sulfatides and gangliosides.

Plasma cholesterol-lowering activity of monocyte colony-stimulating factor (M-CSF).

We investigated the action of monocyte colony-stimulating factor (M-CSF) on plasma cholesterol metabolism. Recombinant human monocyte colony-stimulating factor (rhM-CSF) was intravenously injected into Watanabe heritable hyperlipidemic (WHHL) rabbits that were deficient in LDL receptor. The treated rabbits showed decreases in plasma total cholesterol levels from 493 +/- 39 to 416 +/- 45 mg/dl (about 15%) during the treatment.

Prophylactic and therapeutic effects of oral administration of amphotericin B in mycosis associated with hematologic diseases. Study Group of Mycosis in Hematologic Disease.

The prophylactic and therapeutic effects of the oral administration of amphotericin B (AMPH) to patients with deep mycosis associated with hematologic diseases were evaluated in an investigation including determination of serum concentrations of the antibiotic. Prophylactic effects were examined in 111 subjects, and the efficacy rates averaged 83.8% at daily doses from 1,200 to 4,800 mg.

[Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, with antibiotics in severe infections in the field of internal medicine].

A novel human native immunoglobulin liquid preparation for intravenous injection, C-425, was used in combination with antibiotics to study its efficacy, safety, and usefulness in 262 patients with severe infections which had not responded to antibiotic therapy of 3-day or more duration. As a result of the Committee judgement, 12 of the 262 patients were excluded from this study; 87 were included only in safety analysis; 163 (62.2%) were included in efficacy, safety, and usefulness analyses (complete inclusion).

Characterization and molecular features of the cell surface receptor for human granulocyte-macrophage colony-stimulating factor.

The receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF) on the surfaces of normal and leukemic myeloid cells were characterized using 125I-labeled bacterially synthesized GM-CSF. The binding was rapid, specific, time dependent, and saturable. Scatchard analysis of the 125I-GM-CSF binding to peripheral blood neutrophils indicated the presence of a single class of binding site (Kd = 99 +/- 21 pM; 2,304 +/- 953 sites/cell).

[Reduction of myocardial infarct size by early intracoronary thrombolysis as assessed by serum cardiac myosin light chains and left ventricular function].

Cardiac myosin light chains are released from the infarcted myocardium soon after the onset of infarction, and the level of myosin light chains in the serum reflects infarct size, regardless of the presence of early coronary reperfusion. In this study, we used serum myosin light chains and assessed changes in left ventricular function to evaluate the effects of intracoronary thrombolysis on infarct size, with special reference to the interval between the onset of infarction and the time of reperfusion. Forty patients with acute myocardial infarction who underwent coronary angiography and intracoronary thrombolysis for the left anterior descending artery (LAD) early after the onset of infarction were categorized in four groups: in group A (n = 9) the LAD was already patent at the start of intracoronary thrombolysis, in group B (n = 12) antegrade flow in the LAD was achieved within three hours of the onset of symptoms, in group C (n = 10) antegrade flow was achieved later than three hours after the onset of symptoms, and in group D (n = 9) antegrade flow in the LAD was not achieved.