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Biomedical subjects

T Fujimoto

Publications and source records attributed to T Fujimoto.

At least 19 recordsLinked to original sources

Cell proliferation in childhood acute leukemia. Comparison of Ki-67 and proliferating cell nuclear antigen immunocytochemical and DNA flow cytometric analysis.

The proliferative activity of bone marrow leukemia cells was determined by DNA flow cytometric (FCM) analysis and labeling index (LI) of Ki-67 monoclonal antibodies and proliferating cell nuclear antigen (PCNA) autoantibodies in 73 children with acute leukemia. LI of Ki-67 varied greatly from patient to patient (range, 0.4% to 42.2%; mean, 18.8%) and differed significantly between acute lymphoblastic leukemia (ALL) and acute nonlymphoblastic leukemia (ANLL). In ALL, the Ki-67 LI showed a positive correlation with the S-phase fraction (SPF) determined by DNA FCM analysis, whereas, in ANLL, there was a discrepancy between the Ki-67 LI and SPF. In contrast, LI of PCNA varied less among the patients (range, 57.2% to 100%; mean, 90.3%), and the value was always higher than that of the Ki-67 LI in individual patients. A significant relationship between PCNA LI and the percentage of blast cells was found in peripheral blood leukocytes from patients with leukemia. These results suggest that the Ki-67 LI reflects differences in the proliferative activity depending on the subtype of the disease and that the PCNA LI is useful as a marker of proliferating cells.

Blast Crisis

Histochemical identification and behavior of quail primordial germ cells injected into chick embryos by the intravascular route.

The behavior of quail primordial germ cells (PGC) after injection into chick embryos by the intravascular route was examined. The quail (donor) PGC, taken from the bloodstream of quail embryos (recipient) at stage 13-14, were injected into the vitelline vessels of chick embryos (recipient) at stage 15. In the recipient embryos, the PGC of the quail and the chick were histochemically distinguished by a double-staining technique involving a lectin, from Wistaria floribunda (WFA) and the PAS reaction. One day after injection, quail PGC appeared in the prospective gonadal region of recipient chick embryos, being localized among the recipient chick PGC. This result indicates that a staining technique specific for WFA lectin is useful for identification of quail PGC and that quail PGC can be transferred by a vascular route for the production of germline chimeras.

Animals

[Reevaluation of US and CT findings in adult intussusception].

Computed tomographic (CT) and ultrasonographic (US) findings of 10 adult patients with 11 intussusceptions were retrospectively analyzed. Through close scrutiny of wall structures of intussusceptums and mesenteric fat, new features of adult intussusceptions were found: 1. The returning walls were thicker than the entering walls in 10 of 11 intussusceptums. 2. The neck of the returning wall was thicker than its head in eight of nine intussusceptums. 3. Longitudinal compression of the wall and venous congestion resulting from an inside out turning of the wall structure were thought to be the cause of thickening of the returning wall. 4. Invaginated mesenteric fat tended to be located at the head (apex) in two of seven intussusceptions, making differentiation from intussusception caused by lipoma difficult. 5. The leading masses were detectable as apical soft tissue density masses in eight of 10 intussusceptions. These findings contradict those of previous reports on adult intussusceptions.

Adult

Selective lectin-binding sites of primordial germ cells in chick and quail embryos.

To ascertain the histochemical characteristics of surface carbohydrates on avian primordial germ cells (PGC), we examined the distribution of binding sites for several biotinylated lectins in chick and quail embryos. Some binding sites were detected almost selectively with PGC but not with other embryonic sites. Of these, lectin from Sojanum tuberosum (STA) reacted with PGC in both avian species, whereas lectin from Wistaria floribunda (WFA) and Griffonia simplicifolia II (GS-II) reacted in the quail and the chick, respectively. The binding site for STA was found at the cell surface and cytoplasm of the PGC from their initial appearance in the germinal crescent through migration to sexually indifferent gonads, whereas the WFA reaction was seen at stages before and during migration. These reactivities showed most intensely on the surface of PGC at the peak of their migration. In contrast, GS-II binding site was restricted to the cytoplasm, and its distribution was similar to that of the periodic acid-Schiff (PAS)-positive glycogen granules in chick PGC. These results suggest that some selective binding sites on the PGC surface play a significant role in their migration and show that lectins STA, WFA, and GS-II can be used as probes for identification of the avian PGC.

Animals

Evaluation of basic procedures for adoptive immunotherapy for gastric cancer.

Peripheral blood lymphocytes (PBL) of gastric cancer patients in advanced stages showed lymphokine activated killer (LAK) activities comparable to those of healthy donors, suggesting potential applicability of LAK cells induced from PBL stimulated with recombinant interleukin-2 (rIL-2) in adoptive immunotherapy (AIT) for gastric cancer. In order to generate a large number of LAK cells from PBL, lymphocytes were cultured with both rIL-2 and phytohemagglutinin (PHA). In this culture, the numbers of cells increased to a greater extent than those in culture with rIL-2 alone but cytotoxic activity did not augment, thus suggesting that this procedure would not afford sufficient clinical effects. On the other hand, a large number of LAK cells with high anti-tumor activities were efficiently induced from spleen cells of the patients by culture of rIL-2; hence clinical usefulness of these LAK cells is anticipated. In regional lymph node lymphocytes (RLNL) cultured with rIL-2, the cytotoxic activities were lower than in those induced in PBL, and a characteristic increase of CD8 + CD11 + suppressor T cells was observed after incubation with rIL-2. Nevertheless, an increase of CD4 + 4B4 + helper inducer T cells was also observed in RLNL after the culture with rIL-2. Furthermore, high cytotoxic activities were induced in RLNL in some cases in which metastasis to the regional lymph nodes was not detected. When gastric cancer patients were pretreated with biological response modifiers (BRM), especially with Lentinan, LAK cells from PBL showed higher NK and LAK activities as compared with those of patients without BRM pretreatment.

Adult

Structural transformation of lignan compounds in rat gastrointestinal tract.

Structural transformation of arctiin and tracheloside, major components of seeds of Arctium lappa and Carthamus tinctorius, were investigated using rat gastric juice (pH 1.2-1.5) and rat large intestinal flora in vitro. Quantitative analysis of lignans and their metabolites was carried out by high performance liquid chromatography. Both lignans were stable in rat gastric juice and arctiin was rapidly transformed to arctigenin in rat large intestinal flora, followed by conversion to the major metabolite, 2-(3",4"-dihydroxybenzyl)-3-(3',4'-dimethoxybenzyl)-butyrolactone. On the other hand, tracheloside also decreased dependently with time and was converted to trachelogenin and its major metabolite, 2-(3",4"-dihydroxybenzyl)-3-(3',4'-dimethoxybenzyl)-2-hydroxybutyrola ctone. These experiments suggest that in the course of metabolism of lignans, firstly a cleavage of the glycosidic bond occurred and then demethylation of the phenolic methoxy group in the alimentary tract followed.

4-Butyrolactone

Localization of inositol 1,4,5-trisphosphate receptor-like protein in plasmalemmal caveolae.

Activation of various receptors by extracellular ligands induces an influx of Ca2+ through the plasma membrane, but its molecular mechanism remains elusive and seems variable in different cell types. In the present study, we utilized mAbs generated against the cerebellar type I inositol 1,4,5-trisphosphate (InsP3) receptor and performed immunocytochemical and immunochemical experiments to examine its localization in several non-neuronal cells. By immunogold electron microscopy of ultrathin frozen sections as well as permeabilized tissue specimens, we found that a mAb to the type I InsP3 receptor (mAb 4C11) labels the plasma membrane of the endothelium, smooth muscle cell and keratinocyte in vivo. Interestingly, the labeling with the antibody was confined to caveolae, smooth vesicular inpocketings of the plasma membrane. The reactive protein, with an M(r) of 240,000 by SDS-PAGE, could be biotinylated with a membrane-impermeable reagent, sulfo-NHS-biotin, in intact cultured endothelial cells, and recovered by streptavidin-agarose beads, which result further confirmed its presence on the cell surface. The present findings indicate that a protein structurally homologous to the type I InsP3 receptor is localized in the caveolar structure of the plasma membrane and might be involved in the Ca2+ influx.

Animals

Study of chronic schizophrenics using 31P magnetic resonance chemical shift imaging.

Phosphorus-31 chemical shift imaging showed regional abnormalities of in vivo 31P NMR spectra in the brains of chronic schizophrenic patients. In the left temporal region, the level of % phosphodiesters (PDE) was increased and the level of % gamma alpha beta-ATP (obtained by summation of gamma-ATP, alpha-ATP, and beta-ATP) was decreased. In the basal ganglia, the levels of % PDE were decreased and the level of % phosphomonoesters was increased. The levels of % gamma alpha beta-ATP were increased in the right basal ganglia. The level of % phosphocreatine was decreased in the frontoparietal region. These findings may represent different patterns of dysfunction of membrane phospholipid bilayers and high-energy phosphate metabolism in the specific cerebral regions.

Adenosine Triphosphate

Interaction of platelets and blood vessels--vascular injuries induced by platelet activation in vivo.

We have found that vascular injuries are induced by intravascular aggregation of platelets activated by arachidonic acid (AA) or ADP. The characteristic findings are the appearance of vacuoles in endothelial cells and eventual deendothelialization. In deendothelialized regions, formation of platelet thrombi was observed. The platelets in the thrombi were stained with 2T60, a monoclonal antibody that recognizes activated platelets. The change was more remarkable in the AA-injected animals because AA has a stronger platelet activating effect and a detergent effect on the endothelium. The ADP-injection experiments clarified the role of platelets in vascular injury. These findings suggest that activated platelets play a role in the genesis of vascular injuries, and that their role is related to thrombus formation.

Adenosine Diphosphate

Congestive heart failure in the elderly--echocardiographic insights.

One hundred and seventy-two patients (110 were greater than or equal to 65 years and 62 were less than 65 years) with congestive heart failure (CHF) were prospectively evaluated to determine various pathophysiologic mechanisms of CHF. The incidence of CHF with normal left ventricular (LV) systolic function was higher in elderly (30% vs 12%, p less than 0.05). Of the 110 elderly patients, LV systolic function was impaired in 77. Fifty-five patients had LV dilatation without increased wall thickness, and the clinical diagnosis was "dilated cardiomyopathy in the elderly". Twenty-two patients had hypertrophied LV and a high incidence of hypertension, and they were diagnosed as "hypertensive heart failure" due to contractile dysfunction. On the contrary, the remaining 33 patients did not have impaired LV contractile function. Thirteen patients lacking LV hypertrophy had enlarged atria. CHF was induced by reduced chamber compliance called "the stiff heart syndrome". Twenty patients had hypertrophied LV and a high incidence of hypertension. They were diagnosed as having "hypertensive hypertrophic cardiomyopathy of the elderly" and abnormalities of diastolic function accounted for the CHF. Since echocardiography can easily and accurately diagnose the pathophysiologic mechanism of CHF, an increased awareness of its occurrence in the elderly and use of echocardiography would reduce diagnostic and therapeutic errors.

Aged

A method to obtain avian germ-line chimaeras using isolated primordial germ cells.

Primordial germ cells (PGCs), collected from the blood of 2-day-old chick embryos, were concentrated by Ficoll density centrifugation. The blood contained 0.048% PGCs and the concentrated fraction contained 3.9% PGCs in blood cells. The PGCs were picked up with a fine glass pipette, and one hundred were then injected into the terminal sinuses of 2-day-old Japanese quail embryos (24 somites); bubbles were then inserted to prevent haemorrhage. The embryos were further incubated at 38 degrees C for 24 h, and then fixed. Serial sections were stained with the periodic acid-Schiff reagent (PAS) to demonstrate chicken PGCs and with Feulgen stain to identify quail cells. On the basis of the differences in staining properties, 63.6 +/- 5.3 chick PGCs were detected in the quail embryo in the area where the gonads develop. Furthermore, 39.3 +/- 4.5 chick PGCs were incorporated into the quail germinal epithelium within 24 h of the injection. A similar percentage of the host (quail) PGCs had also migrated to the germinal epithelium at the same stage of development. This technique for obtaining germ-line chimaeras will facilitate research on avian germ-line differentiation.

Animals

Short- and mid-term follow-up results after percutaneous transvenous mitral commissurotomy.

This study reports the clinical follow-up for 6 months of 52 patients who underwent percutaneous transvenous mitral commissurotomy (PTMC). PTMC resulted in an increase in mitral valve area from 1.1 +/- 0.3 to 1.7 +/- 0.4 cm2 (p < 0.0001), a decrease in mean left atrial pressure from 16 +/- 7 to 13 +/- 5 mmHg (p < 0.0001), and an increase in exercise time from 4.6 +/- 2.1 to 6.3 +/- 2.3 min (p < 0.0001). At 6 months follow-up, mitral valve area was unchanged (1.7 +/- 0.4 cm2). Of 52 patients, 33 showed clinical improvement and 19 had no clinical improvement after PTMC. Univariate analysis showed (1) younger age, (2) echocardiographic score of 8 or less, (3) existence of mitral regurgitation of less than grade 2 after PTMC, and (4) amelioration in left atrial dimension, mean pulmonary artery pressure and exercise time after PTMC as correlative factors for clinical improvement. In conclusion, PTMC was an effective procedure for mitral stenosis, especially in younger patients with an echocardiographic score of 8 or less. Change in left atrial dimension was a good indicator of the effectiveness of PTMC.

Adult

[Clinical features of latent dilated cardiomyopathy].

To identify the evidence of presymptomatic manifestations of dilated cardiomyopathy (DCM), we studied 30 patients with latent DCM (mean 37 +/- 14 years) who satisfied the following criteria: 1) left ventricular (LV) systolic function was slightly reduced; 2) LV end-diastolic dimension (< 54 mm) and coronary arteries were normal. The incidence of ECG abnormalities was relatively high; nonspecific ST-T changes were the most common (90%). The incidence of grade 3 or 4 ventricular premature contractions according to Lown's classification on 24 hour ambulatory ECGs was 50%. Perfusion defects were observed in 83% on the thallium-201 images. Right ventricular biopsy showed that the interstitial fibrosis was milder (9 +/- 9%) in the study subjects than in 32 patients with DCM (17 +/- 8%) who were treated in our hospital, but there were no significant differences in the diameters of the myofibers (15 +/- 4 vs 17 +/- 4 microns) between the 2 groups. During the follow-up study, deterioration of LV dysfunction was observed in 3 patients. One patient died suddenly. These findings proved the importance of the early detection and characterization of latent state of DCM.

Adult

[Characteristics of jugular venous pulse and its genesis in Ebstein's anomaly].

To clarify the characteristics of the jugular venous pulse and its genesis in Ebstein's anomaly, 6 patients with Ebstein's anomaly whose mean age was 45 +/- 9 years, and 10 normal subjects with a mean age of 27 +/- 6 years were studied by phono-mechanocardiography and echocardiography. The parameters included the relative height of the jugular "c" wave, the relative timing of the upstroke (Q-Cu interval) and the peak of the jugular "c" wave (Q-Cpeak interval), the relative timing of the upstroke of the carotid artery pulse, the relative timing of tricuspid valve closure (Q-Tc interval), the excursion of the closing motion of the anterior tricuspid leaflet (TV excursion), the distance between the anterior mitral annulus and the septal tricuspid annulus (M-T distance), the area of atrialized right ventricle (ARV area) and the maximum area of the tricuspid regurgitant signal. Among 6 patients with Ebstein's anomaly, tricuspid regurgitation was predominant in 4 and mild in the remaining 2. The results were as follows: 1. A large jugular "c" wave was observed in 4 of the 6 patients. Two patients with large ARV area had giant "c" wave. 2. The interval of the upstroke of the carotid artery pulse and that of the jugular "c" wave was about 39.2 msec. 3. The Q-Tc interval was significantly longer and the TV excursion was significantly greater in the patients than in the normal controls. 4. There was only a weak positive correlation between the Q-Cpeak interval and the Q-Tc interval. No significant correlation was observed between the relative height of the jugular "c" wave and the TV excursion. 5. There was a positive correlation between the relative height of the jugular "c" wave, the ARV area and M-T distance. 6. No obvious correlation was observed between the grade of tricuspid regurgitation and the relative height of the jugular "c" wave. These results suggest that augmentation of the "c" wave of the jugular venous pulse is characteristic of Ebstein's anomaly and that it correlates closely with the severity of displacement of the tricuspid valve and the size of the atrialized right ventricle.

Adult

Cell-cycle-associated expressions of proliferating cell nuclear antigen and Ki-67 reactive antigen of bone marrow blast cells in childhood acute leukemia.

To investigate the growth characteristics of human leukemia cells, the expression of proliferation-associated nuclear antigens was examined in relation to cell cycle phases in marrow blast cells obtained from 37 untreated children with acute leukemia. Ki-67 monoclonal antibody reactive antigen and proliferating cell nuclear antigen (PCNA) were measured by the simultaneous flow cytometric analysis of DNA and nuclear antigens. The percentage of PCNA-positive cells was always higher than that of Ki-67-positive cells in individual patients. The level of PCNA was greatly increased in G1 or early S phase, but was generally stable in S and G2 phases. Accordingly, most of the cells in the proliferative compartments (greater than 2C DNA) showed a high expression of PCNA. In contrast, expression of Ki-67 antigen varied greatly from patient to patient, and differed significantly in different subtypes of the disease. The level of Ki-67 antigen increased with the cell cycle progression, showing maximum expression in late S and G2 phases. However, in most of the patients, a distinct population of Ki-67-negative cells was found not only in G1 phase, but also in the proliferative compartments. These results appear to reflect differences in the proliferative activity of bone marrow blast cells in childhood acute leukemia.

Cell Cycle

[Detection of circulating activated platelets by anti-GMP-140 monoclonal antibodies].

The clinical significance and detection methods for circulating activated platelets are reviewed. It has been recently demonstrated that three kinds of platelet granules, dense granule, alpha-granule and lysosome, have specific membrane proteins; granulophysin, GMP-140 (PADGEM) and CD63 antigen, respectively, and that these specific granule-membrane proteins become exposed on the surface of the activated platelets. It is believed that detection of circulating activated platelets, using monoclonal antibodies specific to these granule-membrane, may be reliable and diagnostic value in thrombotic and prethrombotic diseases. Preliminary clinical studies using 2T60, a newly developed anti-GMP-140 monoclonal antibody, was presented.

Antibodies, Monoclonal

[Overt leukemia from MDS associated with marked basophilia].

A 52-year-old woman was admitted to our hospital because of leukocytosis. She had been diagnosed with RAEB in another hospital in past time. At the admission, the white cell count was 30,900/microliter with blasts (14.0%) and marked basophilia (49.0%). Bone marrow aspiration revealed with 30.2% blasts and 21.1% basophils. Having obtained those results, diagnosis of RAEB in transformation was made. After admission, number of basophils in peripheral blood increased gradually, and level of histamine in serum was elevated significantly. Multiple peptic ulcers in stomach and bowel and high fever were induced due to histaminemia. Despite several therapy she died because of respiratory failure and septisemia. Although the mechanism of basophilia in this patient could not be clarified, there was a possibility that basophilia in this patient might be differentiated from leukemic clone because almost basophils in peripheral blood were mature and those had many granules including metachromasia by stained with toluidine blue.

Basophils

[Clinical significance of the click intervals for the diagnosis of dysfunction of the Medtronic-Hall prosthetic valve].

To investigate the clinical significance of click interval for evaluation of prosthetic valve dysfunction, 20 patients underwent Medtronic-Hall (MH) valve replacement (14 in the mitral position and 6 in the aortic position) were studied by simultaneous high-speed recordings of phonocardiogram, echocardiogram and/or Doppler echocardiogram. Two of the 20 patients, one in the mitral and the other in the aortic position, showed MH valve dysfunction. Eleven patients with normally functioning Björk-Shiley (BS) valve in the mitral position served as controls. Results were as follows: 1. There were usually 3 opening clicks (OC1, OC2, OC3) in patients with normally functioning MH valve in the mitral position. These 3 clicks coincided in timing with the beginning of opening, maximum opening and the end of sliding motion, respectively. Both OC1 and OC2 of the MH valve occurred in similar timing with those of the BS valve (A2-OC1 interval: MH = 65.4 +/- 11.8 msec vs BS = 72.3 +/- 17.2 msec; OC1-OC2 interval: MH = 31.2 +/- 7.7 msec vs BS = 27.3 +/- 6.1 msec). However, OC3 occurred significantly later in MH valve than in the BS valve (OC2-OC3 interval: MH = 32.3 +/- 7.5 msec vs BS = 16.4 +/- 3.8 msec, p < 0.01). 2. There were 2 closing clicks (CC1, CC2) in normally functioning the MH valve in the aortic position. These 2 clicks coincided in timing with the beginning and the end of the closing motion, respectively. Mean value of CC1-CC2 interval in 5 prosthetic patients with normal function was 31.0 +/- 9.6 msec. 3. A patient with malfunctioning MH valve in the mitral position showed a markedly prolonged OC1-OC2 interval, ranging from 66 to 140 msec, and she had multiple diastolic clicks after the OC2 phase. Prolonged OC1-OC2 interval was mainly caused by the delay of appearance of OC2, and it was thought to be due to temporary limitation of opening motion of the valve by valve thrombosis. 4. A patient with malfunctioning MH valve in the aortic position showed a markedly prolonged CC1-CC2 interval (100 msec), and he had a significant severe aortic regurgitation during this phase. At operation, fibrinoid thrombus was attached to the aortic annulus at the side of minor orifice of the valve. Closing motion of the valve was disturbed by this thrombus, and the completion of valve closure was markedly delayed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult