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Biomedical subjects

K Kume

Publications and source records attributed to K Kume.

At least 55 records · Page 3Linked to original sources
PubMed1999

Malignant Adenomyoepithelioma of the Breast:A Case with Distant Metastases.

Adenomyoepithelioma is thought to be a low-grade malignancy, and cases showing malignant behavior are rare. A massive breast tumor with skin invasion in a 60-year-old woman was diagnosed as malignant adenomyoepithelioma. Despite the tumor size and skin invasion, noaxillary lymph node metastases were detected. Light microscopy showed proliferation of tubular structures composed of atypical epithelial and myoepithelial cells and occasional anaplastic cells with mitotic figures extending to the epidermis of the skin. Twenty-four months after the surgery the patient complained of dull pain in the right thigh, and was found to have bone, lung and mediastinal lymph node metastases. There was neither local recurrence nor axillary lymph node metastasis. Subsequent femur fracture was treated by osteotomy. Despite additional chemoradiotherapy, the patient died 43 months after the first operation. Our case and literature review indicated that this tumor tends to show hematogenous metastasis.

Journal Article↗
PubMed1999

Accelerated proliferation of epidermal keratinocytes by the transgenic expression of the platelet-activating factor receptor.

Transgenic mice overexpressing platelet-activating factor receptor (PAFR) have abnormal pigmentation of the ear and the tail, which can progress to melanocytic tumors as the mice age. Histologically, epidermal hyperproliferation and increases in dermal melanocytes are evident. Examination of these transgenic mice at various ages revealed hyperproliferation of the epidermis even 2 weeks after birth which developed as the mice aged. Dermal melanocytes also increased in number with growth. Expression of the PAFR transgene was found in keratinocytes and not in melanocytes, thereby suggesting that PAF does not play a direct role in proliferation of melanocytes. Topical application of a cream containing WEB2086, a specific PAFR antagonist, to the ear and the dorsal skin significantly suppressed the number of BrdU-positive cells in PAFR transgenic mice. These results suggest that PAF plays a modulatory role in the growth of epidermal keratinocytes. PAFR transgenic mice would be a useful model for investigations of skin diseases related to altered proliferation of epidermal keratinocytes including psoriasis.

Animals↗
PubMed1999

Laparoscopic splenectomy using a wall-lifting procedure.

A laparoscopic splenectomy using a hanger wall-lifting procedure is herein described. The patient is placed in the right lateral position. The left lower chest and left abdominal wall are then lifted by three wires in two directions, left laterally and vertical to the abdominal wall. The view of the operative field thus obtained is excellent. The lifting wires and bars do not hinder the movement of the forceps, since the angles of the instruments to approach the spleen are different from those of the wires. A laparoscopic splenectomy using this wall-lifting procedure avoids the usual complications associated with pneumoperitoneum while still being technically comparable to a procedure with pneumoperitoneum.

Humans↗
PubMed1999

Platelet-activating factor receptor is not required for long-term potentiation in the hippocampal CA1 region.

From pharmacological studies, platelet-activating factor (PAF) has been proposed as a retrograde messenger for long-term potentiation (LTP) in the hippocampal CA1 region. We re-examined a possible contribution of PAF to LTP with a more specific approach using mice deficient in the PAF receptor. The PAF receptor-deficient mice exhibited normal LTP and showed no obvious abnormality in excitatory synaptic transmission. We also performed pharmacological experiments on the wild-type mice. Two structurally different antagonists of PAF receptors had no effects on LTP. Furthermore, the application of PAF itself caused no detectable changes in excitatory synaptic transmission. Thus, we conclude that the PAF receptor is not required for LTP in the CA1 region. Introduction

Animals↗
PubMed1999

Asymptomatic amebic colitis in a homosexual man.

We describe case of a 75-yr-old Japanese homosexual man who was diagnosed as having amebic colitis. The present case is unique in that invasive amebiasis has occurred in a homosexual man, because Entamoeba histolytica in homosexual patients is considered to be a nonpathogenic and commensal organism in western countries, and that the patient has not complained of any gastrointestinal symptoms associated with minute colonic lesion of an isolated cecal ulcer. This report indicates that the absence of gastrointestinal symptoms does not rule out invasive amebiasis. Therefore, once the ameba is identified in stool specimens, even in homosexual men, it is important to differentiate pathogenic from nonpathogenic species irrespective of whether the patient is symptomatic, and to treat the patient infected with pathogenic species. By means of this strategy, we can prevent pathogenic ameba from spreading in the community.

Aged↗
PubMed1999

Poor renal accumulation of 99mTc-DMSA in idiopathic tubular proteinuria.

In Japanese patients idiopathic tubular proteinuria presents mainly as asymptomatic tubular low molecular weight proteinuria. This disease has recently been shown to resemble Dent's disease which is characterized by tubular proteinuria, hypercalciuria, rickets and eventual renal failure. We report on 4 children with idiopathic tubular proteinuria. Although they had normal renal function, as evidenced by serum creatinine or creatinine clearance, they had very poor renal accumulation of 99mTc-DMSA and the presence of large amounts of tracer in the bladder. Additionally, the patient with the largest amounts of tubular proteinuria had the poorest renal accumulation of the 4 patients. The renal accumulation of tracer decreased with time from a maximum at 10 min after injection. These findings demonstrate that the tracer, once taken to be confined to the proximal tubular cells, is immediately excreted to the tubular lumen. We suggest that poor renal accumulation of 99mTc-DMSA is very important in elucidating the mechanism of idiopathic tubular proteinuria, and that 99mTc-DMSA renoscintigraphy is useful in the evaluation of the patient's renal function over time.

Adolescent↗
PubMed1999

Platelet-activating factor mediates acid-induced lung injury in genetically engineered mice.

Adult respiratory distress syndrome (ARDS) is an acute lung injury of high mortality rate, and the molecular mechanisms underlying it are poorly understood. Acid aspiration-induced lung injury is one of the most common causes of ARDS, characterized by an increase in lung permeability, enhanced polymorphonuclear neutrophil (PMN) sequestration, and respiratory failure. Here, we investigated the role of platelet-activating factor (PAF) and the PAF receptor (PAFR) gene in a murine model of acid aspiration-induced lung injury. Overexpression of the PAFR gene in transgenic mice enhanced lung injury, pulmonary edema, and deterioration of gas exchange caused by HCl aspiration. Conversely, mice carrying a targeted disruption of the PAFR gene experienced significantly less acid-induced injury, edema, and respiratory failure. Nevertheless, the efficiency of PMN sequestration in response to acid aspiration was unaffected by differences in PAFR expression level. The current observations suggest that PAF is involved in the pathogenesis of acute lung injury caused by acid aspiration. Thus, inhibition of this pathway might provide a novel therapeutic approach to acute lung injury, for which no specific pharmaceutical agents are currently available.

Animals↗
PubMed1999

[Effects of DAC (doxifluridine, adriamycin, cyclophosphamide) chemotherapy in advanced breast cancer patients].

Effects of DAC (doxifluridine (5'-DFUR), adriamycin (ADM), cyclophosphamide (CPA)) chemotherapy were evaluated in seven patients with advanced breast cancer. 5'-DFUR of 600 mg was orally daily, ADM of 40 mg/m2 was administered intravenously (bolus) at day 1 and CPA of 400 mg/m2 was administered intravenously (one shot) at day 1 and day 8. These were repeated as one cycle of 21 days. Two complete responses, three partial responses and two progressive diseases were obtained, and the response rate was 71% (95% confidence interval: 29-96%). The side-effects of more than grade 3 were observed in leucocytopenia (4/7), neutrocytopenia (6/7), anorexia (2/7), nausea or vomiting (2/7) and alopecia (6/7). These results suggest that DAC chemotherapy is a novel, attractive regimen for treatment of advanced breast cancer. The randomized clinical trial is required to elucidate the efficacy of 5-fluorouracil (5-FU) or its analogues and the significance of methods for their administration in management of patients with advanced breast cancer.

Administration, Oral↗
PubMed1998

Conditional expression of the dual-specificity phosphatase PYST1/MKP-3 inhibits phosphorylation of cytosolic phospholipase A2 in Chinese hamster ovary cells.

Stimulation of platelet-activating factor (PAF) receptor induces activation of extracellular signal-regulated kinase (ERK) and cytosolic phospholipase A2 (cPLA2) and release of arachidonic acid in Chinese hamster ovary cells. To determine whether the dual-specificity protein phosphatase PYST1/MKP-3 inhibits phosphorylation of cPLA2, we have generated a cell line that conditionally expresses PYST1 under the control of a tetracycline-regulated inducible system. We found that induction of PYST1 suppressed phosphorylation and activation of cPLA2 as well as ERK. Arachidonic acid release was also reduced by about 30%. Pretreatment of cells with an MEK inhibitor, PD98059, had similar effects on PAF-induced cPLA2 phosphorylation and arachidonic acid release. These experiments demonstrate that expression of PYST1 prevents phosphorylation of a cytoplasmic substrate for ERK. Thus, this inducible system may offer a valuable means of investigating physiological roles of ERK in vivo.

Animals↗
PubMed1998

Primary Non-Hodgkin's Lymphoma of the Breast: A Report of Two Cases.

BACKGROUND: Primary non-Hodgkin's lymphoma of the breast (PBNHL) is a rare neoplasm and PBNHL occuring in a man is extremely rare. METHODS: We report herein two cases of PBNHL and discuss methods of diagnosis and treatment. RESULTS: The first patient was a 35-year-old woman who presented with an elastic-hard mass in her left breast and adenopathy in her left axillary fossa. Mammography and ultrasonography suggested left breast cancer. Frozen sections demonstrated PBNHL histologically. Quadrantectomy of the breast was performed followed by chemotherapy. The second patient was a 65-year-old man with an elastic-hard mass in his left breast and left axillary lymphadenopathy. Mammography and ultrasonography suggested breast cancer or a soft tissue tumor. Intraoperative histological examination revealed a diagnosis of non-Hodgkin's lymphoma (NHL). A simple mastectomy and postoperative chemotherapy were performed and the patient had a good prognosis. CONCLUSION: A multidisciplinary approach including surgery, chemotherapy, andradiotherapy is indispensable in treating PBNHL, after diagnosis by excisional biopsy or aspiration cytology.

Journal Article↗
PubMed1998

Impaired anaphylactic responses with intact sensitivity to endotoxin in mice lacking a platelet-activating factor receptor.

Platelet-activating factor (PAF) is a potent phospholipid mediator with diverse biological activities in addition to its well-known ability to stimulate platelet aggregation. Pharmacologic studies had suggested a role for PAF in pregnancy, neuronal cell migration, anaphylaxis, and endotoxic shock. Here we show that disruption of the PAF receptor gene in mice caused a marked reduction in systemic anaphylactic symptoms. Unexpectedly, however, the PAF receptor-deficient mice developed normally, were fertile, and remained sensitive to bacterial endotoxin. These mutant mice clearly show that PAF plays a dominant role in eliciting anaphylaxis, but that it is not essential for reproduction, brain development, or endotoxic shock.

Anaphylaxis↗
PubMed1998

Functional analysis of a canalicular multispecific organic anion transporter cloned from rat liver.

Transport of many organic anions across the bile canalicular membrane is mediated by the canalicular multispecific organic anion transporter (cMOAT). Previously, we cloned cDNA that may encode cMOAT from Sprague-Dawley rat liver (Ito, K., Suzuki, H., Hirohashi, T., Kume, K., Shimizu, T., and Sugiyama, Y. (1997) Am. J. Physiol. 272, G16-G22). In the present study, the function of this cloned cDNA was investigated by examining the ATP-dependent uptake of S-(2,4-dinitrophenyl)-glutathione (DNP-SG) into membrane vesicles isolated from an NIH/3T3 cell line transfected with an expression vector containing the cloned cDNA. Although the membrane vesicles from the control NIH/3T3 cells exhibited endogenous activity in transporting DNP-SG and leukotriene C4 in an ATP-dependent manner, the transfection of cMOAT cDNA resulted in a significant increase in the transport activity for these ligands. The uptake of DNP-SG into membrane vesicles was osmotically sensitive and was stimulated to some extent by other nucleotide triphosphates (GTP, UTP, and CTP) but not by AMP or ADP. The K(m) and Vmax values for the uptake of DNP-SG by the membrane vesicles were 0.175 +/- 0.031 microM and 11.0 +/- 0.73 pmol/min/mg protein, respectively, for the transfected rat cMOAT and 0.141 +/- 0.036 microM and 3.51 +/- 0.39 pmol/min/mg protein, respectively, for the endogenous transporter expressed on control NIH/3T3 cells. These results suggest that the product of the previously cloned cDNA has cMOAT activity being able to transport organic anions in an ATP-dependent manner. Alternatively, it is possible that the cDNA product encodes an activator of endogenous transporter since the K(m) value for DNP-SG was comparable between the vector- and cMOAT-transfected cells. The transport activity found in the control NIH/3T3 cells may be ascribed to mouse cMOAT since Northern blot analysis indicated the presence of a transcript that hybridyzed to the carboxyl-terminal ATP-binding cassette sequence of the murine protein.

3T3 Cells↗
PubMed1998

Transfected rat cMOAT is functionally expressed on the apical membrane in Madin-Darby canine kidney (MDCK) cells.

PURPOSE: The purpose of the present study is to investigate the expression of canalicular multispecific organic anion transporter (cMOAT) by its cDNA transfection in polarized Madin-Darby canine kidney cells (MDCK). METHODS: MDCK cells were transfected with an expression vector (pCXN2) containing the rat cMOAT cDNA with lipofectamine to obtain the stable transfectant under G418. Cells from a single colony whose cMOAT expression was the highest were seeded to form a tight epithelial monolayer on microporous membrane filters. Export of glutathione S-bimane (GS-B) from monolayers was determined after preloading its precursor, monochloro bimane (MCB). RESULTS: A comparable amount of GS-B was excreted to the apical and basal compartments in the vector-transfected cells. In contrast, in cMOAT-transfected cells, the amount apically excreted was approximately twice that excreted into the basal compartment. Cyclosporin A (CsA) (30 microM), an inhibitor of cMOAT at higher concentrations, inhibited the preferential apical export of GS-B from cMOAT-transfected cells. CONCLUSIONS: Rat cMOAT is functionally expressed on the apical membrane of MDCK cells after transfection.

Animals↗
PubMed1998

In situ expression of platelet-activating factor (PAF)-receptor gene in rat skin and effects of PAF on proliferation and differentiation of cultured human keratinocytes.

Platelet-activating factor (PAF) is a potent lipid mediator that exhibits versatile biologic activities in many diverse systems by binding to a specific cell-surface receptor (PAFR). Although the production of PAF in cultured keratinocytes and fibroblasts has been reported, physiologic roles of this mediator in skin remain unclear. In this study, we examined in situ expression of PAFR gene in rat skin and the effects of PAF on the proliferation and differentiation of cultured human keratinocytes. In rat epidermis, PAFR mRNA expression was found from the basal cells to the granular cells, and strong signals were seen in the stratum spinosum. In cultured human keratinocytes, a 3.8 kb PAFR mRNA expression was demonstrated by northern blotting, and two distinct type transcripts driven by different promoters were detected by reverse transcriptase polymerase chain reaction analysis. Addition of PAF (30-100 nM) to cultured keratinocytes during a growth phase inhibited the proliferation. This effect was receptor dependent, because the inhibition was completely blocked by a PAFR antagonist, WEB 2086 (100 nM). On the other hand, whereas PAF (30-100 nM) alone did not affect the cornified envelope formation during the process of keratinocyte differentiation, WEB 2086 (30-300 nM) accelerated it in a concentration-dependent manner. Addition of PAF (100 nM) reversed the effect of WEB 2086, suggesting that WEB 2086 induced cornification by inhibiting PAF endogeneously produced by keratinocytes in an autocrine manner. Thus, we propose that PAF is an intrinsic regulator of keratinocyte during proliferation and differentiation.

Animals↗
PubMed1998

Combined effects of clenbuterol and various concentrations of protein on performance of broiler chickens.

1. The effects of the beta-adrenergic agonist, clenbuterol (1 mg/kg diet) on the growth and muscle composition in female broiler chickens (14 to 32 d of age) fed on diets containing various concentrations of protein (220, 240 or 260 g protein/kg) were examined. 2. Body weight gain over the 18 d period increased linearly with increasing protein intake. The rate of gain was significantly higher in clenbuterol-treated chickens than in control birds. 3. Dietary clenbuterol increased thigh muscle weight and protein concentration of breast and thigh muscle, regardless of dietary protein content. Protein/DNA ratio in thigh muscle was enhanced by clenbuterol feeding, and the magnitude of difference of the ratio was higher in chickens fed on the 240 and 260 g CP/kg diets than in those fed the 220 g CP/kg diet. 4. It was concluded that clenbuterol-treated chickens require increased dietary protein to maintain maximal growth, and that increased protein consumption is an important factor in improving growth in clenbuterol-fed broilers.

Adipose Tissue↗
PubMed1998

A case of IgA nephropathy in three sisters with thin basement membrane disease.

IgA nephropathy associated with thin basement membrane disease is reported in a 9-year-old female. The diagnosis of IgA nephropathy was made by means of an immunofluorescence investigation, which showed generalized diffuse mesangial deposits. Thin basement membrane disease was identified by electron-microscopic investigations, which disclosed thinning of the basement membrane of several capillary loops and prominence of the lamina densa. Her father, elder sister and younger sister were also found to have hematuria and her sisters were diagnosed as having thin basement membrane disease by renal biopsy. Patients with IgA nephropathy have focal thinning of the glomerular basement membrane, but we consider that urinalysis of the family needs to be done for the diagnosis of familial thin basement membrane disease, when diffuse thinning of the glomerular basement membrane is detected in such patients.

Basement Membrane↗