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Biomedical subjects

O Sakai

Publications and source records attributed to O Sakai.

At least 181 records · Page 10Linked to original sources

A case of primary leiomyosarcoma of the heart.

A 53-year-old male was hospitalized with complaints of cough, fever and backache. Two-dimensional echo-cardiography showed a pericardial echo-free space and a mass in the right atrium. Based on the MRI findings showing a pericardial mass originating from the atrial tumor, the final diagnosis of leiomyosarcoma was made by a percutaneous pericardial biopsy. Despite various therapies, the patient died after 3 wk. Because of its rareness (to date only 25 case reports), a premortem diagnosis of primary cardiac leiomyosarcoma is generally difficult. However, we feel that MRI and a subsequent biopsy is quite useful for making an early diagnosis of this disease.

Biopsy, Needle↗

Renal artery thrombosis in a patient with membranous glomerulonephritis.

A 64-year-old man with renal artery thrombosis (RAT) associated with nephrotic syndrome (NS) is reported. Although this patient was diagnosed as NS due to membranous glomerulonephritis (MGN) and treated with prednisolone, RAT occurred as a result of unknown mechanisms and caused mild renal dysfunction. Creatinine clearance has been about 70 ml/min for 9 years since the onset of RAT. The renal scintigraphic image has not changed since the onset. NS responded to prednisolone therapy initially and at the time of the relapse. Recent data have shown proteinuria levels of less than 0.2 g/day.

Glomerulonephritis, Membranous↗

[A case of hemophagocytic syndrome with multiple myeloma].

A case with multiple myeloma complicated with hemophagocytic syndrome (HS) is presented. Because pancytopenia, liver dysfunction and increase of mature histiocytes in the bone marrow appeared rapidly a diagnosis of HS was made. The patient died of multiple organ failure, despite steroid therapy. Autopsy revealed marked invasion of hemophagocytic histiocytes not only into the bone marrow but also into many other organs such as the liver, lymph nodes and kidneys. HS is a histiocyte proliferative disorders, which is likely to be seen in immunocompromised hosts, but there is no previous report about HS and multiple myeloma.

Bone Marrow↗

Effect of hyperlipidemic serum on cultured mesangial cells.

Hyperlipidemia may contribute to the progression of focal glomerular sclerosis (FGS) in humans and obese Zucker rats. Zucker rats undergo an increase in their plasma low density lipoprotein (LDL), very low density lipoprotein (VLDL) and oxidized lipids, resulting in the development of FGS. We examined the effects of such hyperlipidemic serum on thymidine uptake into cultured mesangial cells. LDL and VLDL both stimulated the overnight uptake of 3H-thymidine at a concentration of below 10 micrograms/ml and inhibited this uptake at over 50 micrograms/ml in the medium. Modified LDL and VLDL after oxidation, however, inhibited this uptake at a concentration of 1 microgram/ml in the medium. Although 20% serum-containing medium stimulated the thymidine uptake by the mesangial cells, the lipoprotein fraction inhibited the uptake, while the lipoprotein-free fraction markedly stimulated it. We conclude therefore that the lipoproteins in hyperlipidemic serum suppress and the lipoprotein-free fraction stimulates mesangial growth. Both may play a role in the development of FGS in rats.

Animals↗

A greater stimulation of vascular smooth muscle cell proliferation by serum from spontaneously hypertensive rats.

In an attempt to delineate the differential characteristics of serum from hypertensives on the proliferation of vascular smooth muscle cells (VSMC), we compare the effect of serum from spontaneously hypertensive rats (SHR) with that from normotensive Wistar-Kyoto rats (WKY) in its ability to stimulate proliferation in VSMC. Cell number determination showed that 10% serum from either of the two strains substantially stimulated proliferation of serially passed cultured VSMC, the effect being significantly greater with SHR serum than with WKY serum. 3H-thymidine incorporation into newly synthetized DNA was also tested after treatment with 10% SHR or WKY serum. A substantial increase in the uptake was noted in response to the rat serum, the effect tending to be greater with SHR serum than with WKY serum. No difference was found between the two strains in cell size determined as intracellular water volume. These data provide the evidence of an increased growth stimulating activity of SHR serum. This abnormality may be superimposed on the already-known innate hyperproliferative capacity of VSMC of SHR, leading to an increase in the deterioration of vascular complications seen in this model.

Animals↗

Captopril ameliorates the posturally induced fall in creatinine clearance in patients with chronic glomerulonephritis.

The clinical usefulness of an angiotensin-converting enzyme inhibitor on the posturally induced fall in creatinine clearance (ClCr) was studied in patients with biopsy-proved chronic glomerulonephritis (CGN). After a change from supine to upright position, ClCr fell significantly in all patients. This fall was significantly ameliorated by the pretreatment with captopril (fall in ClCr 28.8 +/- 14.3% for nontreated vs 16.5 +/- 11.5% for treated patients; n = 12; p less than 0.05). The ameliorating effect was more marked in patients with mesangial cell proliferation (MP) than those without it (fall in ClCr 7.2 +/- 6.3% for MP vs 17.1 +/- 12.3% for no MP; n = 6; p less than 0.05). The results suggest that captopril apparently had a renoprotective effect on the orthostatic acute fall in ClCr in patients with CGN, especially those with MP.

Adult↗

[High-dose cepharanthin therapy of idiopathic thrombocytopenic purpura].

Clinical efficacy of oral high-dose cepharanthin (40-60 mg/day) was evaluated in nine patients with idiopathic thrombocytopenic purpura who were unable to discontinue the administration of adrenocorticosteroids or immunosuppressive drugs. Mean platelet counts significantly (p less than 0.05) rose from 4.5 +/- 0.9 x 10(4)/microliters to 8.9 +/- 4.2 x 10(4)/microliters without any side effects. Two to five months after the initiation of this therapy, 4 patients, including 3 who could discontinue adrenocorticosteroids, kept their platelet counts over 10 x 10(4)/microliters. It was suggested that the oral administration of cepharanthin could be a beneficial and safe strategy for ITP.

Administration, Oral↗

[Successful low-dose etoposide therapy for a case of myelofibrosis with chronic myelogenous leukemia megakaryocytic predominance type].

A 38-year-old woman presented with ear pain and vertigo. No hepatosplenomegaly or lymphadenopathy were found, but her platelet counts markedly rose to 414 x 10(4)/microliters with an increase of megakaryocytes in the bone marrow (859/microliters). Cytogenetic assay revealed positive Ph1 chromosome and rearrangement of the break point cluster region (bcr). Although platelet counts remained under 100 x 10(4)/microliters after the administration of carboquone, a high fever and pancytopenia appeared 31 months later. Bone marrow biopsy showed marked myelofibrosis which was improved by low dose etoposide. This case was thought to be Ph1 positive ET, but it was more compatible with CML megakaryocytic predominance type according to the newly proposed "Hannover criteria for myeloproliferative disorders" and cytogenetic assay.

Adult↗

Extracellular matrix contraction by cultured mesangial cells: an assay system for mesangial cell-matrix interaction.

To investigate the interaction between glomerular mesangial cells (MCs) and extracellular matrix (ECM), we have developed a quantitative assay using a floating culture of MC-populated collagen gel matrix (MCGM). Since MCs can contract such a matrix consisting of type I collagen, MCGM exhibited marked contraction. The apparent cause was tensional interaction between MCs and collagen fibers, because: (1) MCs in the gel attached tightly to surrounding collagen fibers; (2) collagen fibrils surrounding MCs were ordered in a radial array; (3) collagen fibers aggregated around MCs in the contracted gel, but not in an uncontracted gel; (4) cytochalasin B, an actin polymerization blocker, inhibited gel contraction in a dose-dependent manner. We found that this interaction was modulated by some factors. Serum in the medium stimulated the contraction of MCGM. The degree of MCGM contraction was proportional to the number of MCs embedded above 2.3 x 10(4) cells/ml of gel. In MCGM containing a basement membrane-type gel matrix (BGM), gel contraction was increasingly inhibited as the content of BGM rose. Our method is useful for elucidating physiological and pathological interactions between MCs and ECM.

Angiotensin II↗

Mesangial cell behavior in a three-dimensional extracellular matrix.

To understand the role of mesangial matrix in regulating responses of mesangial cells (MCs), particularly as a cause of disease, we examined the behavior of MCs cultured in a three-dimensional extracellular matrix (ECM). Mouse and rat MCs were incorporated into ECM composed of type I collagen gel matrix (CGM) and basement membrane-type gel matrix (BGM), and their shape and proliferation were assessed. The effect of gel matrix on MC migration was also studied. MCs exhibited marked elongation and proliferation in CGM, whereas these behavior were inhibited by increasing the ratio of BGM. Although CGM allowed MC migration, BGM restricted it to a great extent. To identify the cause of our findings, we examined the effects of ECM components in our experimental system. Laminin, fibronectin, type IV collagen, and heparin-like proteoglycans (heparan sulfate and heparin) were each mixed separately with CGM at a concentration of 50 micrograms/ml gel. Whereas fibronectin promoted MC elongation and proliferation, and laminin inhibited MC migration, type IV collagen and heparin-like proteoglycans inhibited all three activities of MCs. Our findings suggest that basement membrane-type mesangial matrix is important in regulating the behavior of MCs in vivo.

Animals↗

A greater stimulation of Na-H antiport in cultured vascular smooth muscle cells by serum from spontaneously hypertensive rats.

We investigated the influence of serum from spontaneously hypertensive rats (SHR) on the Na-H antiport and Na-K pump activity of cultured vascular smooth muscle cells (VSMC). Subjecting the VSMC to rat serum stimulated the ouabain-sensitive 86Rb uptake. This activation of the Na-K pump was significantly greater with the SHR serum than the Wistar-Kyoto rat (WKY) serum. Furthermore, the serum from SHR exhibited a larger Na uptake in the presence of ouabain than that from WKY. A greater 5-(N,N-hexamethylene) amiloride-sensitive Na uptake accounted for this difference. When the Na-K pump was active, serum from either of the two strains did not cause an increase in intracellular Na concentrations. We concluded that serum from SHR produced a more pronounced activation of both the Na-H antiport and the Na-K pump. The study suggests that there are humoral factors in SHR serum which elicit the stimulation of the Na-H antiport, leading to the activation of the Na-K pump of VSMC.

Amiloride↗

Vitamin D3 metabolites increase [Ca2+]i in rabbit renal proximal straight tubule cells.

Vitamin D metabolites exert both acute and chronic influences on proximal tubule function. To further evaluate vitamin D action on the kidney, we examined the immediate effects of vitamin D metabolites on cytoplasmic calcium ion concentration [( Ca2+]i), using fura-2 and patch-clamp method in cultured proximal straight tubule cells of rabbit kidney. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] and 25-hydroxyvitamin D3 [25(OH)D3] evoked a transient rise in [Ca2+]i, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] caused a sustained rise in [Ca2+]i; all effects were dose dependent. [Ca2+]i transient, evoked by 1,25(OH)2D3 alone, was abolished in Ca(2+)-free media. Pretreatment of cells in Ca(2+)-free media with caffeine (4 mM) or ryanodine (1 microM) to deplete Ca2+ store of endoplasmic reticulum or with TMB-8 (5 mM) to block Ca2+ release from storage blunted the effect of 25(OH)D3 on [Ca2+]i but not of 24,25(OH)2D3. Data were also supported by activities of Ca-dependent K channel and show that these three vitamin D metabolites in pharmacological doses increase [Ca2+]i of proximal tubule cells from different sources.

24,25-Dihydroxyvitamin D 3↗

Clinical characterization of drug-induced allergic nephritis.

To elucidate the clinical characterization of drug-induced allergic nephritis (DIAN), we analyzed the cases attending our department. We now report on the 14 cases of DIAN due to administration of penicillin in 2 cases, cephem antibiotics in 6 cases, nonsteroidal anti-inflammatory drugs in 4 cases and new quinolone anticidal drugs in 2 cases. With 1 exception, all these cases reached the stage of acute renal failure after taking these drugs for 2-13 days, followed by characteristic allergic symptoms such as fever, skin eruptions and serum IgE elevation in 5 of the 14 cases. A lymphocyte stimulation test (LST) with the suspected drugs proved to be positive in 10 of the 12 cases examined, and the uptake of 67Ga in the kidneys was extremely positive in all 6 cases examined, reflecting the natural course of this disease. Furthermore, there were some cases where 67Ga accumulated in the kidneys in spite of the negative result of LST examination. In all of these cases, a needle or open renal biopsy was performed, and acute tubulointerstitial nephritis (AIN) was diagnosed. Almost all cases were treated with glucocorticoid for AIN or dialysis for acute uremic symptoms several times. However, 4 of the 14 cases could not return to normal condition in spite of these forms of treatment. We would therefore like to suggest that LST and 67Ga scintigram are useful diagnostic tools for DIAN as an alternative to renal biopsy.

4-Quinolones↗