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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 343 records · Page 19Linked to original sources

[Adenocarcinoma of the lung associated with acute promyelocytic leukemia and miliary tuberculosis].

A 44-year-old man was admitted to the hospital because of acute promyelocytic leukemia. A nodular shadow (2.5 cm in diameter) was seen in the right upper lung field on a chest roentgenogram. During the administration of combination chemotherapy for the leukemia, diffuse granular shadow appeared in all lung fields. Transbronchial lung biopsy findings indicated tuberculosis. The patient was given streptomycin, isoniazid, rifampicin and ethambutol, but the nodular show enlarged and a pleural effusion appeared on the right side. Cytologic examination of the pleural effusion revealed adenocarcinoma. Similar findings were obtained from a second transbronchial lung biopsy. The frequency of association of lung cancer and other malignancy is about 4%. The incidences of primary lung cancer found during the course of active tuberculosis, active pulmonary tuberculosis found during the course of primary lung cancer, and tuberculosis found during the course of acute leukemia are 0.9 to 1.4%, 0.4 to 4.3%, and 2.4 to 4.5%, respectively. To our knowledge, this is the first case in Japan in which adenocarcinoma of the lung was associated with acute promyelocytic leukemia and tuberculosis.

Adenocarcinoma↗

[Management of subarachnoid hemorrhages without detectable aneurysm].

In this study, 21 patients with subarachnoid hemorrhage (SAH) but negative angiography were evaluated. Angiography was performed twice on each patient, that is, on admission and at 2 weeks following admission. All patients had severe headache of sudden onset, a characteristic manifestation of SAH. Clinical grades on admission (Hunt and Kosnik classification) were generally good: 17 patients were in grade I or II and 4 patients were in grade III. SAH was confirmed by the presence of subarachnoid clot on CT in all cases. Based on the distribution of SAH, CT findings were classified into two patterns, i.e., perimesencephalic and non-perimesencephalic patterns. Four patients showed the perimesencephalic pattern and the remaining 17 the non-perimesencephalic. The period of follow-up ranged from 20 days to 11 years 6 months, with a mean of 6 years 10 months. Except for three recent cases, the mean follow-up period in 8 years 9 months. Exploratory craniotomies probing for aneurysms have been performed in four patients, but no aneurysms have been found in any of these cases. Clinical deterioration associated with vasospasm was observed in one patient. A communicating hydrocephalus requiring a shunting procedure was observed in three patients showing the non-perimesencephalic type CT pattern. Rebleeding occurred in one patient who subsequently died of what may be a dissecting aneurysm of the vertebral artery. One patient who was able to return to full activity experienced symptoms attributable to SAH such as frequent headaches and increased fatigability. Complete recovery was observed in the remaining 19 patients. Two of them, however, later died due to myocardial infarction and aging, respectively. Given these generally positive outcomes, it should be possible to inform such patients of the benignity of their condition. Angiography may not demonstrate a ruptured aneurysm on initial examination in all cases of aneurysmal SAH. Serial angiography, however, can provide a definite diagnosis of the dissecting aneurysm. Therefore, repeat angiography, particularly, when possible, digital subtraction angiography, is necessary to rule out aneurysmal SAH. While small aneurysms or microaneurysms are often found through exploratory craniotomy, we do not agree with the opinion that surgery may be appropriate for certain patients with SAH but with negative angiography. The natural history concerning rebleeding in such cases, as well as morbidity and mortality associated with hemorrhage, remains to be defined. Furthermore, there are reservations regarding whether coagulation of these abnormalities with bipolar cautery constitutes definitive treatment.

Adult↗

Reversible pontine ischemia caused by acetazolamide challenge.

We report the findings in a patient with a midbasilar artery stenosis in whom reversible ischemic neurologic deficits developed during cerebral blood flow imaging with acetazolamide challenge. The potential for ischemic complications from acetazolamide challenge is discussed.

Acetazolamide↗

[Proinflammatory cytokine levels in cerebrospinal fluid from children with acute encephalitis].

We investigated interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptor 1 (sTNF-R 1) during the acute stage in the cerebrospinal fluid (CSF) from children with acute encephalitis by means of a sandwich enzyme immunoassay. We divided the 24 children with acute encephalitis into two groups: those who survived without neurological sequelae (Group 1, n = 15), and those who died or were left with sequelae (Group 2, n = 9). The IL-1 beta, IL-6, TNF-alpha and sTNF-R 1 levels in CSF in the two groups were significantly higher than those in control subjects (n = 23). The CSF sTNF-R 1 levels in Group 2 were significantly higher than those in Group 1. Our findings suggest that the IL-1 beta, IL-6 and TNF-alpha in CSF are related to the pathogenesis of acute encephalitis, and that the CSF level of sTNF-R1 during the acute stage of encephalitis is an important index for predicting the neurological outcome.

Acute Disease↗

[Resection of multiple thymoma: a case report].

A 74-year-old male, who had been treated for hypertension at the out-patient clinic, was admitted to our hospital because of an abnormal shadow on a chest radiograph. After diagnosis of thymoma by needle biopsy surgery was carried out on July 6, 1995, when an extended thymectomy along with removal of the entire tumor was done. During the surgery it was noticed that there was not one, but two independent tumors located in the anterior mediastinum, the upper left portion was growing from the level of the crania to the left brachiocephalic vein, whereas the lower right portion was growing towards the right thoracic cavity in front of the pericardium. Both tumors were encapsulated firmly, and connected to each other by scantly loose connective tissues. There was no continuity or sarring between the two tumors. Histologically both were diagnosed to be lymphocytic thymoma. We believe that this case is a good example of multiple thymomas and provides evidence of the potential multicentricity of thymoma. It is possible that extended thymectomy may be seeded for a complete resection of thymomas.

Aged↗

Direct extracranial-intracranial bypass for children with moyamoya disease.

To improve cerebral hypoperfusion in the ischemic type of Moyamoya disease, we have applied superficial temporal artery-middle cerebral artery (STA-MCA) double anastomoses in combination with encephalo-myo-synangiosis (EMS) for 19 hemispheres of 10 children (age from 5 to 11 years at surgery). Two branches of the STA were anastomosed to the two cortical arteries which were selected in the watershed area of the cerebral hemisphere estimated as a hypoperfusion area on the preoperative angiograms. Before surgery transient ischemic attacks (TIAs) developed from every month to every 6 months in association with hyperventilation or sobbing. No perioperative completed stroke or wound complications was observed, although single TIA developed in four patients within 1 month after surgery. Postoperative angiogram demonstrated that, not only the preoperative watershed area, but also the most of the middle cerebral artery territory was oppacified via the 2 branches of the STA in all 19 hemispheres. In a mean follow-up period of 4 years, no ischemic episode was induced by hyperventilation, and there was no mental or neurological deterioration. STA-MCA double anastomoses, to the cerebral watershed area, in combination with EMS are safe and effective even for younger children with Moyamoya disease.

Anastomosis, Surgical↗

[Acute myelogenous leukemia (M4) occurring during chronic lymphocytic leukemia].

A 68 year-old-man was first found to have CLL with IgG, kappa monoclonal gammopathy 6 years ago. Bestrabucil (total dose 35,150 mg) was taken orally from August 1989 to December 1989. Etoposide (total dose 23,100 mg) was then orally administered from January 1990 to December 1995. He was then referred to our hospital in January 1996 because of progressive anemia and thrombocytopenia. Peripheral blood showed a WBC of 21,200/microliter with 4% myeloblasts and 79% lymphocytes, Hb 7.9 g/dl and Plt 5 x 10(4)/microliter. The serum level of lysozyme was increased (75.6 micrograms/ml). Bone marrow aspiration disclosed hyper-cellularity with proliferation of the blasts and a monocytoid cell population, which cytochemical studies demonstrated to be of the myelo-monocytic series, thus indicating acute myelogenous leukemia (AML-M4) superimposed on CLL. Surface marker analysis of bone marrow mononuclear cells revealed reactivity for CD 11c, CD13, CD15, CD33, HLA-DR. The karyotype was normal. Southern blot analysis and reverse transcriptase-polymerase chain reaction did not reveal rearrangement of the MLL gene. Complete remission was achieved by chemotherapy consisted of BHAC, idarubicine, 6MP, vincristine and predonisolone. Long-term treatment with oral etoposide may contribute to secondary AML.

Aged↗

Construction of a novel conjugative plasmid harboring a GFP reporter gene and its introduction into animal cells by transfection and trans-kingdom conjugation.

We have established a novel method of gene introduction into eukaryotic cells by trans-kingdom conjugation between Escherichia coli/Agrobacterium tumefaciens bacteria and yeasts. To expand this to animal cells, we have constructed a novel conjugative plasmid, pBASGreen which contains SV40-ori/promoter, pUC-ori, IncQ type oriT/mob, Apr and Neor genes with GFP (green fluorescent protein) gene as a reporter. The introduction into COS1 and NIH3T3 animal cultured cells by conventional transfection was easily detected by fluorescence of the GFP gene product under a fluorescent microscope and the transfectants were effectively selected by the Neor marker. By the action of oriT/mob in the presence of tra genes on a helper plasmid, pBASGreen was directly mobilizable from E. coli into animal cells by trans-kingdom conjugation.

3T3 Cells↗

Effect of short- and long-acting beta 2-adrenoceptor agonists on pulmonary beta 2-adrenoceptor expression in human lung.

beta-Adrenoceptor agonists induce the down-regulation of beta 2-adrenoceptors and mRNA expression in animal lung. The down-regulation of beta 2-adrenoceptors may limit the therapeutic efficacy of beta 2-adrenoceptor-mediated bronchodilators in obstructive airways disease. We examined the effects of three selective beta 2-adrenoceptor agonists, salbutamol, salmeterol and formoterol on beta 2-adrenoceptor binding and mRNA levels in human lung in vitro. Human lung was obtained from cardiac transplantation donors. Peripheral lung was chopped and incubated with three selective beta 2-adrenoceptor agonist for 3 h or 24 h at three different concentrations (0.1, 1 and 10 microM). The affinity and density of beta 2-adrenoceptors was determined by [125I]iodocyanopindolol equilibrium binding in a lung membrane preparation in the presence of 0.1 microM CGP 20712 A (1-{2-[(3-carbamoyl-4-hydroxy)phenoxy] ethylamino}-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl) phenoxy]-propan-2-ol), a selective beta 1-adrenoceptor antagonist. Although treatment with salbutamol for 3 h did not change beta 2-adrenoceptor density, both salmeterol and formoterol reduced beta 2-adrenoceptor density, and exposure to each agonist for 24 h reduced beta 2-adrenoceptor density at all concentrations. Treatment with 10 microM salmeterol increased the equilibrium dissociation constant (Kd), and also shifted the competition curves of (-)-isoprenaline to the left, beta 2-Adrenoceptor mRNA, measured by Northern blot analysis using a human beta 2-adrenoceptor cDNA probe, was reduced after exposure to all beta 2-adrenoceptor agonists at 3 h. Our data provide evidence for down-regulation of beta 2-adrenoceptor protein and mRNA after selective beta 2-adrenoceptor agonist treatment in human lung.

Adolescent↗

Oxygen-dependent regulation of energy metabolism in ascites tumor cells by nitric oxide.

To understand the role of nitric oxide (NO) in the regulation of energy metabolism of tumor cells, its effect on the respiration and calcium homeostasis was examined with ascites hepatoma (AH130) cells under different oxygen tensions. NO reversibly inhibited the respiration and depolarized the membrane potential of AH130 cells in an oxygen-dependent manner; the inhibition was more marked at physiologically low oxygen concentrations than at its high tensions. NO reversibly decreased the cellular ATP levels and elevated the cytosolic calcium, particularly under low oxygen concentrations. Since the peritoneal cavity is fairly anaerobic, the results suggested that small amounts of NO generated in this compartment might strongly affect the energy metabolism and calcium homeostasis of tumor cells in vivo.

Adenosine Triphosphate↗

Uncleaved env gp160 of human immunodeficiency virus type 1 is degraded within the Golgi apparatus but not lysosomes in COS-1 cells.

The fate of newly synthesized human immunodeficiency virus type 1 env gp160 was examined in COS-1 cells. The results of morphological chase experiments involving cycloheximide demonstrated that gp160 was retained in the Golgi apparatus for longer than the half-life of the molecule. The degradation of gp160 was insensitive to both bafilomycin A1 and leupeptin (< 0.2 mM), which block lysosomal proteolysis. However, degradation was effectively suppressed by leupeptin at higher concentrations, maximally at 1.7 mM. Furthermore, undegraded gp160 was accumulated in the Golgi apparatus, but was not detected in lysosomes. These results indicate that in COS-1 cells gp160 is not degraded in lysosomes, but rather that degradation takes place in the Golgi apparatus.

Animals↗

Localisation and expression of beta-adrenoceptor subtype mRNAs in human lung.

The cellular localisation and distribution of mRNAs encoding beta-adrenoceptor subtypes in human lung were studied by in situ hybridisation and Northern blot analysis. The 851-bp SmaI/PvuII fragment of human beta 1-adrenoceptor cDNA, the 439-bp SmaI fragment of human beta 2-adrenoceptor cDNA and the 975-bp SmaI fragment of human beta 3-adrenoceptor cDNA bound to single mRNA species of approximately 3.2 kb, 2.2 kb and 2.3 kb in size, respectively. Human lung and heart and rabbit lung expressed both beta 1- and beta 2-adrenoceptor mRNAs with no detectable level of beta 3-adrenoceptor mRNA, while rabbit perirenal adipose tissue expressed beta 1-, beta 2- and beta 3-adrenoceptor mRNAs. Cultured human airway epithelial cells and airway smooth muscle cells expressed only beta 2-adrenoceptor mRNA. In situ hybridisation in human lung, using 35S-labelled antisense RNA probes revealed a high level of expression of beta 1- and beta 2-adrenoceptor mRNAs in the pulmonary blood vessels, high level of expression of beta 2-adrenoceptor mRNA in the alveolar walls with less expression of beta 1-adrenoceptor mRNA. There was a moderate expression of beta 2-adrenoceptor but not beta 1-adrenoceptor mRNA in airway epithelium and smooth muscle of peripheral airways and no detectable beta 3-adrenoceptor mRNA in any lung structures.

Animals↗

Proctolinlike immunoreactivity and identified neurosecretory cells as putative substrates for modulation of courtship display behavior in the blue crab, Callinectes sapidus.

Pheromonally stimulated courtship display (CD) behavior in male blue crabs (Callinectes sapidus) is characterized by rhythmic waving of the fifth legs. The waving of the fifth legs is modulated by proctolin in freely moving crabs and in reduced preparations. To begin to identify an anatomical substrate for CD behavior we have localized putative proctolinergic cells and described the morphology of neurosecretory neurons known to oscillate during pheromonal stimulation of reduced preparations. Proctolin-induced CD occurs with developmental and seasonal dependence. Male crabs altered hormonally by eyestalk ligation spontaneously produce CD behavior. We have localized proctolinlike immunoreactivity (PIR) in the central nervous system (CNS) and compared this immunoreactivity across sexes, developmental stage, eyestalk ligation, and seasonal conditions to determine whether or not expression of PIR is correlated with CD behavior. PIR was found in most areas of the CNS. Clusters of PIR-positive cells were found in the sinus gland and eyestalk ganglia, olfactory neuropil with associated cell bodies, and in a large cell cluster in the subesophageal region of the ventral nerve cord. Three pairs of cell bodies in different cell body groups in the brains of adult crabs stained positively for PIR but did not stain in the youngest juvenile animals. Comparison of PIR distribution with toluidine blue studies of the ventral nerve cord indicated a high likelihood that cells in the PIR-positive cluster of the subesophageal ganglia were also members of the cluster of neurons identified as oscillatory neurosecretory neurons.

Animals↗

1 alpha,25-dihydroxyvitamin D3-induced upregulation of calcineurin during leukemic HL-60 cell differentiation.

Cyclosporin A and FK506, at concentrations that inhibited phosphatase activity of calcineurin in HL-60 cellular lysates, augmented the proliferation of leukemic HL-60 cells. These immunosuppressants did not affect 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]-induced monocytic differentiation of HL-60 cells, but did abrogate the 1,25(OH)2D3-induced inhibition of HL-60 cell growth. Treatment with 20 nmol/L 1,25(OH)2D3 led to a progressive increase in calcineurin phosphatase activity in subcellular fractions from HL-60 cell extracts, the increase in this activity appeared to parallel the phenotypic and functional changes of HL-60 cells during monocytic differentiation induced by 1,25(OH)2D3. Immunoblot analysis indicated that increase in calcineurin activity was concordant with the increased expressions of calcineurin catalytic subunit isozymes, calcineurin A alpha (CNA alpha), and calcineurin A beta(CNA beta), and a regulatory calcineurin B subunit (CNB) proteins, which were preceded by a coordinate increase in the levels of CNA alpha, CNA beta and CNB mRNAs. The expression of calmodulin remained unaltered throughout 1,25(OH)2D3-induced monocytic differentiation. These results suggest that calcineurin activation has a net negative effect on HL-60 cell proliferation, and that the increased expression of calcineurin may be involved in 1,25(OH)2D3-induced inhibition of HL-60 cell proliferation.

Calcineurin↗

Role of superoxide anions in airway hyperresponsiveness induced by cigarette smoke in conscious guinea pigs.

To investigate the involvement of superoxide in airway hyperresponsiveness and bronchoconstriction induced by cigarette smoke (CS), we evaluated the effects of superoxide dismutase (SOD), a scavenger of superoxide anion, and apocynin, an inhibitor of superoxide anion-generating NADPH oxidase in phagocytes, on the airway responses induced by CS in conscious guinea pigs. Airway responsiveness was assessed by PC200Mch, the concentration required to produce a doubling in the baseline specific airway resistance (sRaw) to an inhaled methacholine aerosol, in nonanesthetized spontaneously breathing animals. Before being exposed to ten puffs of CS, animals inhaled either SOD (5,000 units/ml or 25,000 units/ml) or vehicle. Although SOD did not affect PC200Mch in the air control group, this agent significantly reduced the CS-induced airway hyperresponsiveness. Repeated administration of apocynin (12 mg/kg for 4 days) did not affect PC200Mch after exposure to CS. These data suggest that the superoxide from CS was involved in the airway hyperresponsiveness induced by CS, whereas phagocytic reactive oxygen species were not. The data also suggest a potential therapeutic role for antioxidants in airway hyperresponsiveness.

Acetophenones↗

Cerebrospinal fluid levels of soluble tumour necrosis factor receptor in acute encephalitis.

Soluble tumour necrosis factor receptor (sTNF-R) inhibits the action of TNF-alpha. The level of sTNF-R reflects the true biological activity of TNF-alpha. We investigated whether sTNF-R in cerebrospinal fluid (CSF) and serum increases during the acute stage in patients with acute encephalitis by measuring p60 sTNF-R using a sandwich enzyme immunoassay. The levels of sTNF-R were significantly higher in the CSF and serum of children with acute encephalitis than in those of control subjects. The patients with acute encephalitis who died or had severe neurological sequelae had higher CSF sTNF-R levels than those who survived. There were no significant differences in the serum sTNF-R, serum C-reactive protein and CSF protein levels, and CSF cell counts between the two groups. The sTNF-R levels of 4.0 ng/ml or higher identified patients with acute encephalitis who had neurological sequelae with a sensitivity of 100% (8/8), a specificity of 100% (8/8%), and a predictive value of 100% (8/8). The 95% confidence interval for these three values is 63-100%. Our findings suggest that the CSF level of sTNF-R during the acute stage of encephalitis is important for predicting neurological sequelae.

Acute Disease↗