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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 379 records · Page 21Linked to original sources

Thyroid cell proliferation-inhibiting activity in serum of patients with chronic renal failure on hemodialysis.

To investigate the possible humoral factor(s) influencing thyroid cell activity in chronic renal failure, we measured serum activity which stimulates or inhibits the [3H]thymidine incorporation by using a cultured functioning rat thyroid cell line (FRTL-5 cells) in 17 patients on hemodialysis and 19 healthy controls. Polyethylene glycol-treated serum was centrifuged and FRTL-5 cells were cultured with the supernatant. Thyroid stimulating activity was determined by [3H]thymidine incorporation after incubation for 72 h. There was no significant difference in [3H]thymidine incorporation between cultures incubated with patient and normal serum, suggesting the absence of the stimulating activity. But when patient serum was added to cultures together with 20 or 50 microU/ml of TSH, the TSH-stimulated increase in [3H]thymidine incorporation was significantly decreased, indicating the presence of thyroid inhibiting activity, which possibly inhibits the thyroid cell growth. This activity was not significantly altered by hemodialysis. No significant correlation was observed between this activity and serum levels of thyroid hormones or the iodine concentration. Patients on hemodialysis therefore have serum thyroid inhibiting activity which is nondialysable, differs from iodine, and could influence the thyroid cell growth.

Adult↗

Plasma free thyroxine (FT4) concentrations during hemodialysis in patients with chronic renal failure: effects of plasma non-esterified fatty acids on FT4 measurement.

Plasma free T4 (FT4) concentrations could be increased during hemodialysis in patients with chronic renal failure (CRF) because an increase in non-esterified fatty acids (NEFA) could interfere with the binding of T4 to thyroxine-binding globulin. To evaluate the effect of hemodialysis on the FT4 concentration in patients with CRF, we measured the FT4 in 39 patients with CRF by four assay methods including equilibrium dialysis, the 125I-T4 analog method and enzyme immunoassay. The addition of the fatty acid sodium oleate to normal pooled sera led to a marked increase in FT4 as measured by equilibrium dialysis (Model FT4). A moderate increase in the serum FT4 concentration also was observed with an IMX enzyme immunoassay kit, whereas the Coat-A-Count analog method demonstrated no interference by sodium oleate. The mean serum FT4 prior to hemodialysis measured by equilibrium dialysis did not differ significantly from that in the normal control, although those measured by analog methods (Coat-A-Count and Amerlex) and IMX were subnormal. The FT4 by IMX were albumin-dependent, and the values decreased as the samples were serially diluted, but Model FT4 was not affected by the albumin level or the serial dilution. FT4 by Model FT4 showed a marked increase beginning 10 min after the start of dialysis, and it correlated well with the plasma concentration of NEFA and the NEFA/albumin molar ratio. The other three assay methods, including one which is not affected by NEFA, did not show a change in FT4 at 10 min, but a significant increase of 11 to 17% was observed by the end of dialysis. The TSH concentration decreased significantly during hemodialysis. These data suggest that (1) the low serum FT4 in hemodialysis patients measured by some immunoassay methods may be an underestimation due to the low albumin level; (2) FT4 actually increases during hemodialysis due to the actual increase in NEFA, although the marked increase in FT4 during hemodialysis as measured by equilibrium dialysis is an overestimation due to the in vitro generation of NEFA; and (3) one should beware of aberrations in thyroid hormone parameters during hemodialysis and potential complications.

Dialysis↗

Non-traumatic arteriovenous fistulas of the scalp treated by a combination of embolization and surgical removal.

Three patients with non-traumatic arteriovenous fistulas (AVFs) of the scalp were treated by embolization using acrylate glue through the transarterial route or by direct puncture of the lesions and then surgical resection. Complete cure was achieved in all three patients. Selective angiography is indispensable in the correct diagnosis of scalp AVFs. Embolization facilitates surgical removal when necessary, and this combination is the treatment of choice for scalp AVFs.

Acrylates↗

Transient monocular blindness during manual carotid compression for carotid-cavernous sinus fistulas--two case reports.

Transient monocular blindness occurred during manual carotid compression in two patients with a traumatic direct and a spontaneous dural arteriovenous carotid-cavernous sinus fistula. Ocular complication may occur during diagnostic or therapeutic carotid compression for carotid-cavernous sinus fistulas, so patients should be informed of this possibility. Ocular examination should be repeated during carotid compression to prevent sequelae of ischemic oculopathy.

Arteriovenous Fistula↗

Vein of Galen aneurysmal malformation in a neonate treated by endovascular surgery--case report.

A male neonate with vein of Galen aneurysmal malformation developed fetal heart failure after a gestation period of 37 weeks. Labor was induced, but a cesarean section had to be performed because of fetal distress. His Apgar scores were 2/8 at birth. The boy required controlled ventilation due to generalized seizure and cyanosis. Neuroimaging revealed vein of Galen aneurysmal malformation with enormous arteriovenous shunt flows. Transarterial embolization was performed on days 4 and 6 to reduce the progressive high-output congestive heart failure. Three large feeders were occluded with interlocking detachable coils, markedly reducing the shunt flow. Although heart failure improved markedly, he died of pulmonary hemorrhage on day 12. Endovascular surgery can improve the prognosis of heart failure in the neonatal period less invasively than other treatment modalities, and may help to minimize ischemic brain damage and thus increase the possibility of normal brain maturation.

Arteriovenous Fistula↗

[Vertebral artery dissection without subarachnoid hemorrhage studied by serial angiography].

We presented six cases we have encountered of vertebral artery dissection without subarachnoid hemorrhage followed by serial angiography. All six patients suffered from severe headache and/or nuchal pain at onset. Pain was acute at onset, with severe intensity and sharp quality and was located unilaterally on the dissection side. Only two patients showed neurological deficits. CT scan disclosed no abnormalities in any of the cases and angiography performed at the acute stage showed varied findings. The so-called pearl and string sign, which has been considered the most common finding of this disorder, was observed in only two cases. The definite diagnosis was able to be finally made by serial angiography. During the first few months after onset, dynamic changes of angiographical findings were demonstrated in all cases. During these periods, although transient deterioration of the angiographical findings was shown in four cases, spontaneous healing or improvement was finally recognized in all cases except one which progressed to total occlusion. In contrast to this, in the chronic stage, no changes of angiographical findings occurred in any of the cases. All six patients were treated non-surgically. All showed almost total recovery from symptoms and returned to their previous life styles. There were no cases of recurrent deterioration of symptoms in spite of the changes indicated by the angiographical findings. Our experience with these patients suggests that the actual incidence of vertebral artery dissection without subarachnoid hemorrhage may be much higher than is usually thought, and that the natural course of this disorder seems to be usually favorable. However, longer follow-up study and an analysis of a larger number of cases are required to identify the true incidence and the natural course of this disorder. In addition, we would like to emphasize that accurate diagnosis is most important. If it is clinically suspected, careful investigations including serial angiography should be carried out for the diagnosis of this disorder.

Adult↗

[A case of rheumatoid factor-positive pachymeningitis].

We report a case of rheumatoid pachymeningitis involving the posterior fossa. A 71-year-old woman presented with headache, vertigo and dizziness. MRI demonstrated hypertrophic masses in the meninges of the left cerebellar tentorium, cerebellopontine angle and the fourth ventricle. Six months of treatment with betamethasone, prednisolone and azathioprine improved the patient's neurological status. Because an inappropriate immune process and systemic immune disease may cause idiopathic pachymeningitis, the performance of immunological studies for idiopathic cases is mandatory.

Aged↗

Granulocyte-colony stimulating factor and stem cell factor are the crucial factors in long-term culture of human primitive hematopoietic cells supported by a murine stromal cell line.

The findings that murine marrow stromal cell line MS-5 supported the proliferation of human lineage-negative (Lin-) CD34+CD38- bone marrow cells in long-term culture have been reported. In this study, we analyzed this proliferating activity of MS-5-conditioned medium (CM) on human primitive hematopoietic cells. When Lin-CD34+CD38- cells of normal human cord blood cells were co-cultured with MS-5, colony forming cells (CFCs) were maintained over 7 weeks in vitro. Prevention of contact between MS-5 and Lin-CD34+CD38- cells by using membrane filter (0.45 micron) was negligible for this activity. This indicated that the activity of MS-5 on human primitive hematopoietic cells is a soluble factor(s) secreted from MS-5, which is not induced by the contact between MS-5 and Lin-CD34+CD38- cells. We tried to purify this soluble activity. An active material with a molecular weight of about 150 kDa, determined by gel filtration chromatography, solely supported the growth of Lin-CD34+CD38- cells and Mo7e, a human megakaryocytic cell line. This activity not only reacted with anti-mouse stem cell factor (mSCF) antibody on Western blots, but it was also neutralized in the presence of anti-mSCF antibody. Another active material with a molecular weight of about 20-30 kDa synergized with mSCF to stimulate the growth of Lin-CD34+CD38- cells but failed to do so alone, although this synergy was inhibited in the presence of soluble mouse granulocyte-colony stimulating factor (mG-CSF) receptor, which is a chimeric protein consisting of the extracellular domain of mG-CSF receptor and the Fe region of human IgG1. In addition, the latter molecule supported the growth of the G-CSF dependent cell line FD/GR3, which is a murine myeloid leukemia cell line, FDC-P2, transfected with mG-CSF receptor cDNA. Adding of anti-mSCF antibody and soluble mG-CSF receptor to the culture completely abrogated the activity of MS-5-CM. Recombinant (r) mSCF and rmG-CSF had synergistic activity on the growth of Lin-CD34+CD38- cells. These results indicated that the activity on Lin-CD34+CD38- cells included in MS-5-CM is based upon the synergistic effects of mSCF and mG-CSF.

ADP-ribosyl Cyclase↗

Mechanism of elevated local oxidant stress in early anti-glomerular basement membrane nephritis: an evaluation of oxidant production and superoxide dismutase expression.

The present study was designed to identify the mechanism of increased oxidant stress in the rat model of anti-glomerular basement membrane nephritis. Sixty-three Sprague-Dawley rats were injected with nephrotoxic serum and evaluated 1 to 24 hours later. In these rats, CeCl3 deposition, an index of hydrogen peroxide production, was observed on the surfaces of glomerular endothelial cells and polymorphonuclear leukocytes, whereas no such depositions were observed in controls. Renal cortical level of lipid peroxidation products (phosphatidylcholine hydroperoxide) was significantly (p < 0.05) elevated at one hour after the injection and remained elevated at least for 24 hours. Protein levels of glomerular Mn-superoxide dismutase (SOD) decreased from 1.55 +/- 0.38 microgram/mg protein to 0.67 +/- 0.18 microgram/mg protein at one hour and normalized by 12 hours after the injection. The activity of the enzyme showed a similar trend. In contrast, Mn-SOD mRNA increased 3.4-fold at 3 hours after the injection. In situ hybridization showed increased Mn-SOD mRNA expression in glomeruli. Cu/Zn-SOD mRNA expression was transiently suppressed. These results indicated that both increase in local production of reactive oxygen species (ROS) and reduction in antioxidant enzyme activities are responsible for the enhanced oxidant stress in the heterologous phase of anti-glomerular basement membrane nephritis. The paradoxical increase in Mn-SOD mRNA expression indicates that the posttranscriptional down regulation of Mn-SOD (i.e., reduction in protein and activity) and the increased ROS may activate transcription of the gene.

Animals↗

Differential association of protein Ser/Thr phosphatase types 1 and 2A with the cytoskeleton upon platelet activation.

The association of protein Ser/Thr phosphatase type 1(PP1) and type 2A (PP2A) with the cytoskeleton (Triton X-100 insoluble residue) during human platelet activation was investigated. In unstimulated platelets, 40% of total PP1-like activity was present in the Triton-insoluble cytoskeleton, while only 10% of the total PP2A-like activity was present in this fraction. Stimulation with 1 U/ml thrombin produced a 1.8-fold increase in PP1-like activity and a 7-fold increase in PP2A-like activity, respectively, in the cytoskeletal fraction, under aggregating conditions. Immunoblot analysis revealed that thrombin treatment increased association of PP1 catalytic subunit isozymes (PP1 alpha, PP1 gamma, PP1 delta) and PP2A catalytic subunit with the cytoskeleton, with concomitant decrease of these enzymes in Triton-soluble fractions. The amounts of cytoskeleton-associated PP1 and PP2A depended on the dose of thrombin which could activate platelets. Agonist-induced redistribution of PP1 and PP2A into the cytoskeleton was inhibited by OP-41483 (a prostaglandin I2 analog). Interaction of PP2A with cytoskeletal proteins strongly correlates with aggregation, whereas the association of PP1 with cytoskeleton can be detected upon platelet activation, even in the absence of aggregation. Co-extraction of protein kinase C and myosin light chain kinase with the cytoskeleton eventually translocated to the cytoskeleton, but only during aggregation. These results suggest that differential translocation of PP1 and PP2A to the cytoskeleton is involved in platelet activation, and their association with cytoskeletal proteins may regulate phosphorylation levels together with protein kinases in platelets.

Cytoskeleton↗

[Airway hyperresponsiveness and airway mucosal permeability].

The relationship between airway mucosal permeability and airway hyperresponsiveness was examined with tachykinins, their selective antagonists, and superoxide dismutase in male Hartley guinea pigs. In animals with ozone-induced airway inflammation, airway hyperresponsiveness and mucosal permeability increased concurrently but there was a time lag before the increase in airway vascular permeability. To study the role of tachykinins in the increases in mucosal permeability and in hyperresponsiveness, we used a neurokinin-receptor antagonist, CP-96345, and a neurokinin-2 receptor antagonist, SR-48968. CP-96345 had no significant effect, but SR-48968 reduced the increase in airway mucosal permeability; their effects on airway hyperresponsiveness were the opposite of their effects on airway permeability. Tachykinins themselves, both substance P and neurokinin A, significantly increased airway mucosal permeability. Superoxide dismutase, a scavenger enzyme of superoxide, reduced the ozone-induced airway hyperresponsiveness. These data suggest that the factors causing airway hyperresponsiveness differ from those that influence mucosal permeability, but it is possible that these pathophysiologic conditions are caused by the same substances or processes.

Animals↗

Up-regulation of protein serine/threonine phosphatase type 2C during 1 alpha,25-dihydroxyvitamin D3-induced monocytic differentiation of leukemic HL-60 cells.

Treatment with 20 nM 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) caused a progressive increase in the activity of Mg(2+)-dependent protein serine/threonine phosphatase type 2C (PP2C) in subcellular fractions of HL-60 cells, whereas PP2C activity was relatively constant throughout all-trans retinoic acid-induced (1 microM) granulocytic differentiation. The increase in PP2C activity appeared to parallel the 1,25(OH)2D3-induced phenotypic and functional changes in HL-60 cells. Immunoblot and Northern blot analysis indicated that the increase in PP2C activity corresponded to the increased expression of PP2C protein, which was preceded by an increase in the level of mRNA for PP2C beta. No mRNA for PP2C alpha was detected in resting or 1,25(OH)2D3-stimulated HL-60 cells. These results suggest that the increased expression of PP2C is related with the 1,25(OH)2D3-induced monocytic differentiation of HL-60 cells.

Calcitriol↗

Central projections of the antennal cold receptor neurons and hygroreceptor neurons of the cockroach Periplaneta americana.

The central projections of the cold receptor axons were examined by filling two types of cold receptive sensilla with cobalt lysine--a cold and hygroreceptive (C/H) sensillum and a cold receptive and olfactory (C/O) sensillum--on the antennae of the cockroach, Periplaneta americana L. When the dye filled a single C/H sensillum, four axons were stained. Three of these axons terminate in the ipsilateral antennal lobe, while the other branches in the ipsilateral dorsal lobe. One of the branches passed through the tritocerebrum to terminate in the suboesophageal ganglion, while the other branches end in the lobe. When a single C/O sensillum is dye filled, all axons of the four receptor neurons terminate exclusively in the ipsilateral antennal lobe. One axon from the C/H sensillum and one axon from the C/O sensillum terminate in a particular glomerulus in the ventroposterior region of the antennal lobe. Each of these axons also has a tuft in separate glomeruli situated just dorsal to the glomerulus in which both axons terminate. This set of three glomeruli have indistinct boundaries and appear to form a complex of glomeruli similar to the macroglomerular complex of male moths. Assuming modality-specific convergence of antennal afferents, these axons appear to belong to the cold receptor neurons, and the set of glomeruli appear to function in cold reception. Two other neurons stained from C/H sensilla always terminate in the glom-eruli distinct from the set of glomeruli mentioned earlier. These neurons are assigned to the pair of hygroreceptor neurons, and their glomeruli are thought to function in hygroreception.

Animals↗

The effects of dietary fiber from Lagenaria scineraria (yugao-melon) on colonic carcinogenesis in mice.

BACKGROUND: The increasing trend of colon cancer in Japan is attributed to changes in dietary habits, that is, increased amounts of fat and decreased amounts of fiber in the diet. The effects of Japanese dietary fiber from Lagenaria scineraria (yugao-melon) on colonic carcinogenesis in mice were examined. METHODS: Eighteen ICR mice in each group were fed with either a basal diet or a diet containing 5%, 10%, or 20% of yugao powder for 35 weeks. All the mice received a weekly intraperitoneal injection of 1,2-dimethylhydrazine (DMH), 10 mg/kg body weight for 10 weeks. The effects of yugao powder on the mucosal and luminal variables involved in colonic carcinogenesis were then compared with those of wheat bran in the mice without any carcinogen treatment. RESULTS: The incidence of colon tumors (adenocarcinomas) was lower in the yugao powder diet groups than in the basal diet group at week 35 (24% vs. 50%, P < 0.05). The bile acid concentration in the colon was reduced in all the fiber diet groups except for the 5% yugao powder diet group. The colonic luminal pH acidified as yugao powder contents also increased in the yugao powder diet groups. The findings on the colonic short chain fatty acids, microflora, and mucosal fatty acids and ornithine decarboxylase activity were all inconsistent with a tendency to either develop or to inhibit carcinogenesis in both the fiber diet groups. CONCLUSIONS: Dietary fiber from yugao-melon suppressed DMH-induced colonic carcinogenesis in mice by lowering the bile acid concentration and pH in the colon. The results of the luminal and mucosal variables examined also suggested that the mechanisms of action of yugao powder against colonic carcinogenesis differed from those of wheat brain.

Adenocarcinoma↗

Translocation of protein phosphatase 1 catalytic subunits during 1,25-dihydroxyvitamin D3-induced monocytic differentiation of HL-60 cells.

To elucidate the roles of protein phosphatases type 1 (PP1) and type 2A (PP2A) in 1,25-dihydroxy-cholecalciferol [1,25(OH)2D3]-induced differentiation of HL-60 cells into monocytes, we examined the enzyme activity and the protein and gene expressions of PP1 and PP2A in these cells. Calyculin-A augmented the 1,25(OH)2D3-induced differentiation of the cells. Treatment of the cells with 1,25(OH)2D3 led to a decrease in PP1-like activity in the cytosol fraction, with a concomitant increase in the membrane and nuclear PP1-like activity, as determined when protein phosphatase activity was assayed using myosin light chain as substrate in the presence of 5 nM okadaic acid. Western blot analysis with antibodies specific for PP1 catalytic subunit isozymes (PP1 alpha, PP1 gamma, and PP1 delta) showed that all three PP1 isozymes were expressed but were differentially distributed in each cellular fraction. Subcellular redistribution of PP1-like activity during 1,25(OH)2D3-induced differentiation was mainly attributed to PP1 gamma and PP1 alpha proteins. In contrast, the localizations of PP1 delta and PP2A catalytic and regulatory subunits were not significantly affected by 1,25(OH)2D3 treatment. The gene expressions of PP1 alpha and PP1 gamma appeared to be constant during processes of monocytic differentiation. The correlation between phenotypic and functional changes of HL-60 cells on the one hand and subcellular redistribution of PP1-like activity on the other suggest that the translocations of PP1 alpha and PP1 gamma isozymes may contribute to the 1,25(OH)2D3-induced monocytic differentiation of HL-60 cells.

Calcitriol↗