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Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 577 records · Page 32Linked to original sources
PubMed1993

FK-506: a new immunosuppressive agent, failed to reduce cerebral vasospasm after experimental subarachnoid hemorrhage.

To define the relationship between the immunologic reaction and the pathogenesis of cerebral vasospasm (VS) following experimental subarachnoid hemorrhage (SAH), we examined the effect of a cell mediated immunosuppressive agent, FK-506, isolated from Streptomyces tsukubaensis, by using the canine SAH model. There was a significant vasoconstriction in the basilar artery in the control group after SAH. This constriction, however was not successfully prevented by FK-506 or combination of FK-506 and steroid, since there was no significant difference in the vessel caliber size among these groups. The pathologic approach, accompanied by immunohistochemistry, could not discriminate the differences in the nature of the lesion between the untreated group and FK-506 treated groups, except for slight lymphocytic infiltrations present around the basilar artery of untreated group. Histopathologically, inflammatory reactions consisting of neutrophils, that were not suppressed by FK-506 treatment, were clearly seen around the spastic vessels in the subarachnoid space. Furthermore, several constrictive changes or degenerative alterations were also observed in the spastic vascular wall. Immunohistochemically, the deposition of IgG, IgM and C3 was present in the intima and the luminal side of the smooth muscle layer, and capillary vessels of the brain stem. It is considered that this deposition was caused by increased vascular permeability in VS. On the basis of the above findings that the cell mediated immunosuppressive agent, FK-506 failed to prevent vasoconstriction or pathologic lesions but lymphocytic infiltrations, it is considered that the cell mediated immunopathogenesis may play little role in producing VS following SAH.

Animals↗
PubMed1993

Angiotropic lymphoma of paranasal sinuses with initial symptoms of oculomotor nerve palsy.

A 78-year-old female was found to have angiotropic lymphoma, a rare fatal disease, with initial symptoms of oculomotor nerve palsy. A biopsy of the paranasal sinus mucosa showed that the small vessels were occupied by large mononuclear cells which upon immunohistochemical examination tested positive for pre B-cell markers. She felt a gradually increasing pain in her left thigh. Magnetic resonance imaging suggested the involvement of neoplastic cells in the left femoral bone marrow. Following chemotherapy treatment remission was achieved. Early diagnosis of angiotropic lymphoma appears very significant, as this disorder could be well controlled by systemic chemotherapy.

Aged↗
PubMed1993

Meningioangiomatosis not associated with von Recklinghausen's disease--case report.

A 7-year-old girl with meningioangiomatosis not associated with von Recklinghausen's disease is described. The radiological findings were similar to meningioma, but intraoperatively, a thin septum was found between the mass and the dura mater. Microscopically, there was significant proliferation of fibroblastic spindle-shaped cells and collagenous fibers in the subarachnoid space. Proliferated cells had penetrated into the cortical tissue along the irregularly branched blood vessels. Immunohistochemically, these penetrating perivascular cells were negative for glial fibrillary acidic protein and S-100 protein, and positive for vimentin staining. These findings suggest that the histogenesis of the spindle-shaped cells is most probably meningothelial.

Child↗
PubMed1993

Failure of FK-506, a new immunosuppressant, to prevent cerebral vasospasm in a canine two-hemorrhage model.

In order to clarify the possible role of immunological reaction in the pathogenesis of cerebral vasospasm, the authors examined the prophylactic effect of the immunosuppressant agents FK-506 and cyclosporin A on chronic vasospasm in a canine two-hemorrhage model. While a mean constriction of the basilar artery to 81.0% +/- 4.0% (+/- standard error of the mean) occurred on Day 2 and to 63.8% +/- 3.5% on Day 7 in the untreated group, constriction to 77.9% +/- 3.4% on Day 2 and 62.8% +/- 3.0% on Day 7 was demonstrated in the FK-506-treated group (difference not significant). This tendency was also noted in the cyclosporin A-treated group, with basilar artery constriction to 81.8% +/- 3.7% and 56.3% +/- 2.7%, respectively (difference not significant). The histological changes of the basilar artery, including corrugation of the elastic lamina, detachment of endothelial cells, and vacuolar formation in the smooth-muscle layer were not different in the two treated groups and the one control group. Since these immunosuppressant agents are known to inhibit the release of interleukin-2 (IL-2), the level of IL-2 was examined in the cerebrospinal fluid of patients with cerebral vasospasm. While interleukin-1 gradually increased in level as time passed, the level of IL-2 was consistently low during the course of the study, indicating less participation of IL-2 in the pathogenesis of cerebral vasospasm. This clinical observation matched the experimental results. The authors conclude that cell-mediated immunoreaction, initiated mainly by IL-2, plays little role in the pathogenesis of cerebral vasospasm.

Animals↗
PubMed1993

Effects of stem cell factor (SCF) on the in vitro growth of leukemic blast progenitors in acute non-lymphocytic leukemia.

We studied the effects of recombinant human stem cell factor (SCF) on the growth of leukemic blast progenitors obtained from 27 acute non-lymphocytic leukemia (ANLL) patients and 1 chronic myelocytic leukemia patient in myeloid crisis; the effects varied among the patients. While SCF did not have stimulatory effects in the cells of 7 patients, it stimulated primary and secondary blast colony formation in methylcellulose culture and the recovery of clonogenic cells in suspension cultures from 21 patients. SCF stimulated leukemic blast progenitors in a manner almost comparable to or more prominently than that of other CSFs, namely, IL-3, GM-CSF, and G-CSF, in 9 patients. One patient responded to SCF but not to the other CSFs. In another 11 patients, SCF was less effective on leukemic blast progenitors than the other CSFs tested. To explain the variable effects of SCF, we investigated the relation between the phenotype of leukemic blasts and responsiveness to this agent; the response was significantly higher in patients with CD34-positive blasts than in those with CD34-negative blasts. These results imply that responsiveness to SCF differs among leukemic blast progenitors originating at different hematopoietic stages. In some ANLL patients, SCF showed synergy with other CSFs, suggesting that SCF may be involved in the cytokine network affecting leukemic hematopoiesis.

Adolescent↗
PubMed1993

Philadelphia-chromosome-positive, monosomy 7 biphenotypic acute mixed lineage leukemia in adults: a pluripotent stem cell disorder.

Two adult patients with acute mixed lineage leukemia (AMLL) having combined Philadelphia chromosome (Ph1) positivity and monosomy 7 are presented. The phenotypes of leukemic blasts from both cases were almost same (early B-lymphoid lineage and myeloid lineage); CD10+, CD13+, CD19+. HLA-DR+, and dual-color analysis showed simultaneous expression of CD10 (CD19) and CD13 antigens in individual blasts (biphenotypic) in both cases. On molecular analysis, the leukemic blasts showed rearrangement in the first intron of the BCR gene with breakpoint just outside of 3' end of m-BCR-2 (bcr 3) in case 1, and in the M-BCR in case 2. Immunoglobulin heavy chain gene (IgH) rearrangement was noted in both cases, but rearrangement of the T-cell receptor beta-chain gene (TCR beta) was detected only in case 1. Clinically, both cases achieved complete remission by the combination chemotherapy consisting of L-asparaginase, doxorubicin, vincristine, and prednisolone (L-AdVP). In remission, all these molecular abnormalities disappeared in both patients. These results suggest that the Ph1-positive and monosomy 7 AMLL in adults is de novo acute leukemia with both early B-lymphoid and myeloid phenotypes and may arise from malignant transformation of pluripotent stem cell, and expresses a heterogenous rearrangement pattern of the BCR gene.

Acute Disease↗
PubMed1993

Solitary bone plasmacytoma terminally developed myeloma with multiple extramedullary lesions and myelomatous pleural effusion and ascites.

A rare case of IgG-kappa type multiple myeloma associated with multiple extramedullary tumor-forming lesions and myelomatous pleural effusion and ascites is reported. The patient suffered from sternal solitary plasmacytoma, which 5 years later developed disseminated tumor formation with myeloma cells mostly in the soft tissues. At autopsy, multiple extramedullary lesions particularly in the abdominal cavity and myelomatous pleural effusion and ascites were observed without diffuse infiltration of myeloma cells in the bone marrow. The disseminating change from solitary bone plasmacytoma to extramedullary tumor formation seen in this case seemed to be unusual but suggestive of a feature of an aggressive tendency of multiple myeloma.

Abdominal Neoplasms↗
PubMed1993

[Successful treatment by ranimustine (MCNU) of a patient with B-cell prolymphocytic leukemia (B-PLL)].

A 66-year-old female was admitted to our hospital because of leukocytosis, anemia and splenomegaly in August 1989. The white cell count was 3.49 x 10(10)/l with 88.5% of the leukemic cells which were morphologically similar to prolymphocytes. On flowcytometric analysis, the leukemic cells were found to be positive for B-cell markers such as CD19, CD20, FMC7, Sm-IgM and Sm-IgD and negative for CD5 and CD25. The chromosome analysis demonstrated hyperdiploidy of 48, XX, (+3, +18). She was diagnosed as having B-cell prolymphocytic leukemia, and treated with alpha-interferon and VP therapy with progression. Complete remission was achieved after three courses of ranimustine (MCNU) administration. She relapsed after about one year without therapy, but when MCNU was administered again, a secondary remission followed. The prolymphocytes during the relapse stage also had the phenotypes of CD11b, CD13 and CD25. This case is considered to be rare with respect to both complete remission by MCNU and the immunophenotypic change of leukemic cells during the relapse period.

Aged↗
PubMed1993

[Usefulness of blood disappearance corrected hepatic uptake ratio (LHL/HH) as a hepatic functional index using 99mTc-galactosyl serum albumin].

The authors introduced blood disappearance corrected hepatic uptake ratio (LHL/HH) as an index of hepatic function using 185 MBq/3 mg of 99mTc-galactosyl serum albumin (GSA). Three ratio parameters, the hepatic uptake ratio (LHL15), blood disappearance ratio (HH15), and LHL15 divided by HH15 (LHL/HH) were evaluated with percent injected dose of 99mTc-GSA in blood at 15 min after injection (%ID15) and hepatic functional severity graded by Child-Turcotte criteria score. Seventy eight patients with chronic liver disease were studied. There was a poor linear correlation between the LHL15 and %ID15, because the LHL15 formed a plateau phase in the lower-value range for %ID15. In contrast, LHL/HH showed an excellent linear correlation with %ID15 in its whole range. In the comparison with the clinical functional severity, LHL/HH gave a more highly significant difference (p < 0.001) than LHL15 (p = 0.005) between the normal and mild dysfunction groups and gave a significant difference (p = 0.032) between the mild and moderate groups, in which HH15 showed no meaningful difference (p = 0.07). This index is obtained with no difficult procedures and can be regarded as a unified parameter for hepatic uptake and blood disappearance. It is hoped that LHL/HH will prove useful in the diagnosis of hepatic functional severity using 99mTc-GSA.

Adult↗
PubMed1993

Hypertriglyceridemia in nephrotic rats is due to a clearance defect of plasma triglyceride: overproduction of triglyceride-rich lipoprotein is not an obligatory factor.

This study was conducted to determine whether overproduction of triglyceride-rich lipoprotein is an obligatory factor for experimental hypertriglyceridemia in nephrotic rats. Nephrosis was induced in male Wistar rats by administration of 150 mg/kg puromycin aminonucleoside. Nephrotic rats had slightly increased triglyceride secretion rate (TGSR) estimated using Triton WR1339 (0.53 +/- 0.05 vs. 0.45 +/- 0.04 mg/min, P < 0.05 vs. control rats) and marked hypertriglyceridemia (330.4 +/- 78.6 mg/dl). Rats made diabetic by 40 mg/kg streptozotocin were normotriglyceridemic (66.3 +/- 12.1 mg/dl) but had suppressed TGSR (0.33 +/- 0.09 mg/min). Experimental nephrosis was induced in diabetic rats. Their TGSR remained suppressed (0.35 +/- 0.06 mg/min) but they had marked hypertriglyceridemia (296.6 +/- 72.4 mg/dl) suggesting further impairment of triglyceride removal from the circulation in diabetic rats caused by nephrosis. Endogenously radiolabeled very low density lipoprotein (VLDL)-triglyceride from donor rats was reinjected into normal recipient rats. [3H]VLDL from the experimental groups (the rats with nephrosis, diabetes with nephrosis, and diabetes alone) were more slowly cleared by normal rats than VLDL from normal rats. These results suggest that circulating insulin is essential for increased triglyceride secretion in experimental nephrosis and that nephrotic hypertriglyceridemia can be induced only by a triglyceride removal defect. Therefore, hypersecretion of triglyceride-rich lipoprotein is not an obligatory factor for nephrotic hypertriglyceridemia.

Animals↗
PubMed1993

Orthostatic hypotension: with particular reference to experimentally-induced orthostatic hypotension in dogs.

Blood pressure (BP) and heart rate (HR) were measured while standing in a stable position for SPF beagle dogs consisting of 4 females with an average weight of 8.73 +/- 0.58 kg and average age of 7.38 +/- 0.12 months. No anesthetic was used during the procedure. These dogs were subjected to a postural change, a 90 degrees-tilt standing position, and BP and HR were measured one minute and ten minutes later. In addition, 20 mg/kg of tetraethyl-ammonium bromide (TEA) as a gangliolytic drug was administered by i.v. injection within 30 seconds, and then BP and HR were measured in the resting state for 20 minutes. When changing from the resting position to the 90 degrees-tilt standing position after administration of TEA, these were significant decreases in systolic BP, diastolic BP and mean arterial BP one minute and ten minutes later. An experimental model of orthostatic hypotension was considered to have been achieved during these methods.

Animals↗
PubMed1993

Species differences in stereoselective metabolism of mephenytoin by cytochrome P450 (CYP2C and CYP3A).

Stereoselective involvement of hepatic cytochrome P450 in the metabolism of mephenytoin was investigated in vitro by using livers of five different experimental animal species and humans. The rates of microsomal 4'-hydroxylation were 2 to 6 times higher with the R-enantiomer than the S-enantiomer in rabbits, dogs and rats, whereas the rates of the 4'-hydroxylation in female mice were not different between R- and S-enantiomers. Preferential S-mephenytoin 4'-hydroxylation was observed in monkeys as similar to that in humans. The rates of microsomal mephenytoin N-demethylation were approximately 2 times higher with the R-enantiomer than the S-enantiomer in male rats and both sexes of dogs. Antibodies raised against CYP2C11 (anti-CYP2C) clearly inhibited microsomal 4'-hydroxylation of S-mephenytoin and N-demethylation of R-mephenytoin in rats, monkeys and humans. Antibodies raised against CYP3A2 (anti-CYP3A) clearly inhibited microsomal 4'-hydroxylation of R-mephenytoin, but marginally S-mephenytoin, in rats. Anti-CYP3A, however, showed no clear inhibition on microsomal 4'-hydroxylation and N-demethylation of both enantiomers in monkeys and humans, except for slight inhibition of R-mephenytoin 4'-hydroxylation in male monkeys. The results suggest that stereoselective involvement of rat CYP3A and scant involvement of human CYP3A in R-mephenytoin 4'-hydroxylation are major determinants of the species differences between rats and humans in stereoselective mephenytoin 4'-hydroxylation.

Adult↗
PubMed1993

[The effects of pharmacological autonomic blockade on the conduction system in patients with and without sinus node dysfunction].

Electrophysiological studies were performed in 26 patients with sick sinus syndrome (SSS) and 12 controls before and after pharmacologic autonomic blockade (PAB) with propranolol (0.15 mg/kg) and atropine (0.04 mg/kg). Sinus cycle length (SCL) shortened significantly after PAB in both groups. PA and HV intervals did not change after PAB. AH interval shortened and Wenckebach period increased after PAB in SSS group. Maximum corrected sinus node recovery time shortened in the control group but did not change in the SSS group after PAB. Calculated sinoatrial conduction time shortened after PAB in both groups. Refractory periods of the atrioventricular (AV) node and the ventricle shortened significantly, but those of the atrium did not change after PAB. Linear relations existed between the change of SCL and the change of AH interval and of the Wenckebach period. These results suggested that the autonomic nervous system had the same effects on the sinus and the AV nodes in patients with SSS, and that parasympathetic tone was predominant on the sinus node, the perinodal tissue and the AV node under resting conditions.

Atropine↗