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Biomedical subjects

S Umehara

Publications and source records attributed to S Umehara.

At least 19 recordsLinked to original sources
PubMed2005

Baroreflex control of heart rate during and after propofol infusion in humans.

BACKGROUND: This study was designed to determine cardiovagal baroreflex gain during propofol infusion and to characterize its recovery profile using the pharmacological and spontaneous sequence methods in 13 healthy volunteers without cardiovascular or autonomic disorders. METHODS: After an 8- to 10-h fast and no premedication, measurements of RR intervals obtained from the electrocardiogram and non-invasive beat-to-beat systolic blood pressure (SP) were made at conscious baseline, at 60 and 120 min after induction of general anaesthesia using propofol, and at 20, 60, 120 and 180 min after emergence from anaesthesia. During propofol anaesthesia, ventilation was mechanically controlled to maintain normocapnia and calculated propofol concentration was adjusted by a TCI system at 5 microg ml(-1). Baroreflex responses were triggered by bolus i.v. injections of phenylephrine and nitroprusside to alter SP by 15-30 mm Hg. The linear portions of the baroreflex curves relating RR intervals and SP by least-square regression analysis were determined to obtain pharmacological gains. In addition, spontaneous sequence baroreflex gains were calculated from spontaneously fluctuating SP and RR intervals. RESULTS: Baseline pressor and depressor test gains before propofol anaesthesia were 29.1 (SD 14.9) and 12.5 (7.8) ms mm Hg(-1), respectively. They were significantly depressed by 65-73% during propofol infusions. Similarly, baseline up- and down-sequence baroreflex gains were 33.8 (28.9) and 27.3 (19.8) ms mm Hg(-1), respectively, and were significantly depressed by 71-87% during propofol anaesthesia. Pressor test and up-sequence baroreflex gains returned to the baseline values 20 min after emergence from propofol anaesthesia, but depressor test and down-sequence baroreflex gains did not recover until 60 min after emergence. CONCLUSIONS: We conclude that heart rate responses to both lowering and elevating blood pressure were depressed by propofol anaesthesia, and 60 min was required for their full recovery after discontinuation of propofol infusion.

Adult↗
PubMed2004

Differential expression of natural killer cell receptors (CD94/NKG2A) on T cells by the stimulation of G-CSF-mobilized peripheral blood mononuclear cells with anti-CD3 monoclonal antibody and cytokines: a study in stem cell donors.

We investigated the expression of the inhibitory NKR (CD94/NKG2A) of the G-CSF mobilized peripheral blood mononuclear cells (G-PBMC) on T cells after stimulation for 7 days by immobilized anti-CD3 monoclonal antibody (mAb) with or without cytokines. We demonstrated increased expression of CD94/NKG2A on CD3+/CD8+ T cells. Also, addition of IL-12 induced significantly more CD94/NKG2A expression than addition of IL-15: CD94+CD3+/NKG2A+CD3+; 43.8 +/- 11.6%/33.7 +/- 11.4% by IL-12 versus 32.8 +/- 13.2%/21.3 +/- 9.6% by IL-15, respectively (n = 9, P < .05). However, >90% purified CD94+ cells CD94+ obtained from IL-15-treated G-PBMC by magnetic cell sorting (MACS) exhibited higher cytolytic (CTL) activity against K562 cells than that from IL-12-treated G-PBMC: E:T = 20:1, 40.7 +/- 18.4% vs 15.1 +/- 5.2% (n = 5, P < .05). Therefore, the cytokine effects on inhibitory NKR expression on T cells and CTL activity are differently regulated. Based on these findings, it may be possible to establish the effective strategy to expand inhibitory NKR-expressing T cells with CTL activity for cell therapy.

Antibodies, Monoclonal↗
PubMed2001

Histopathology (International Neuroblastoma Pathology Classification) and MYCN status in patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group.

BACKGROUND: The International Neuroblastoma Pathology Classification (International Classification), which was established in 1999, is significant prognostically and is relevant biologically for the evaluation and analysis of patients with neuroblastic tumors (NTs). MYCN amplification is a known molecular marker for aggressive progression of NTs. These have been used together as important prognostic factors to define risk groups for patient stratification and protocol assignment. METHODS: A total of 628 NTs (535 neuroblastomas [NBs]); 21 ganglioneuroblastoma, intermixed [GNBi]; 9 ganglioneuromas [GN]; and 63 ganglioneuroblastoma, nodular [GNBn]) from the Children's Cancer Group studies were evaluated histologically (favorable histology [FH] tumors vs. unfavorable histology [UH] tumors) according to the International Classification and were tested molecularly for MYCN status (amplified vs. nonamplified). Four tumor subsets (FH-nonamplified, FH-amplified, UH-nonamplified, and UH-amplified) were defined by histopathology and MYCN status, and their prognostic effects were analyzed. Detailed analysis between morphologic indicators (grade of neuroblastic differentiation and mitosis-karyorrhexis index [MKI]) and MYCN status was done by using tumors in the NB category. RESULTS: There were 339 FH-nonamplified tumors (5-year event free survival [EFS], 92.1%); 8 FH-amplified tumors (EFS, 37.5%); 172 UH-nonamplified tumors (EFS, 40.9%); and 109 UH-amplified tumors (EFS, 15.0%). The prognostic effects on patients with tumors in the four subsets were independent from the factors of patient age and disease stage (P < 0.0001). MYCN amplification was seen almost exclusively in tumors of the NB category, and no patients with tumors in either the GNBi category or in the GN category and only two patients with tumors in the GNBn category had amplified MYCN. Among the patients with tumors in the NB category, patients with FH-nonamplified tumors (309 patients) had an excellent prognosis, and patients with UH-amplified tumors (107 patients) had the poorest clinical outcome in any age group. The prognosis for children with UH-nonamplified tumors (111 patients) was poor when they were diagnosed at age > 1.5 years. It was also noted that patients with UH-amplified tumors (median age, 2.14 years) were diagnosed at a significantly younger age compared with the patients with UH-nonamplified tumors (median age, 3.55 years). Histologically, MYCN-amplified tumors lacked neuroblastic differentiation regardless of the age of patients. MYCN amplification also was linked generally to increased mitotic and karyorrhectic activities. However, MKI classes in patients with MYCN-amplified tumors varied significantly, depending on the age at diagnosis, and younger patients had higher MKI classes. CONCLUSIONS: The combination of histopathologic evaluation and MYCN status distinguishes four clinical and biologic tumor subsets in patients with NTs. MYCN amplification seems to be the powerful driving force for preventing cellular differentiation regardless of patient age and for increasing mitotic and karyorrhectic activities in an age dependent manner.

Adolescent↗
PubMed2001

International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group.

BACKGROUND: The International Neuroblastoma Pathology Classification was established in 1999 for the prognostic evaluation of patients with neuroblastic tumors (NTs). METHODS: Pathology slides from 746 NTs (the Children's Cancer Group [CCG]-3881 and CCG-3891 studies) were evaluated according to the International Classification. First, prognostic effects of the morphologic indicators (grade of neuroblastic differentiation: undifferentiated [U], poorly differentiated [PD] and differentiating [D]; and mitosis-karyorrhexis index [MKI]: low [L-MKI], intermediate [I-MKI], and high [H-MKI]) for tumors in the neuroblastoma (NB) category were tested. Then, prognostic significance of the International Classification for all NTs in four categories (neuroblastoma [NB]; ganglioneuroblastoma, intermixed [GNBi]; ganglioneuroma [GN]; and ganglioneuroblastoma, nodular [GNBn]) was analyzed. Finally, age distribution of the patients in the four categories as well as three subtypes (based on the grade of differentiation) in the NB category was compared. RESULTS: There were 630 NB tumors, 30 GNBi tumors, 10 GN tumors, and 76 GNBn tumors. In the NB category, prognostic effects of the indicators (three grades of differentiation and three mitosis-karyorrhexis index [MKI] classes: low [L], intermediate [I], and high [H]) were affected significantly by the age of the patients. The age-linked evaluation of the indicators according to the International Classification successfully distinguished two prognostic subgroups: the favorable histology (FH) subgroup (PD/D and L/I-MKI tumors in patients age < 1.5 years, D and L-MKI tumors in patients ages 1.5-5.0 years; 90.4% 5-year event free survival [EFS]) and the unfavorable histology (UH) subgroup (U and/or H-MKI tumors in patients of any age, PD and/or I-MKI tumors in patients ages 1.5-5.0 years, any grade of differentiation, and any MKI class in patients age > or = 5 years; 26.9% EFS) (P < 0.0001). The International Classification also distinguished the FH group (FH subgroup with NB, GNBi, and GN tumors) and the UH group (UH subgroup with NB and GNBn tumors) for all NTs (90.8% EFS and 31.2% EFS, respectively; P < 0.0001) and provided independent prognostic information on both patient age and disease stage (P < 0.0001). Among patients with FH tumors, the median ages of patients with the PD and D subtype tumors in the NB category were 0.43 years (range, 0-1.50 years) and 1.50 years (range, 0.02-4.65 years), respectively, and the median ages of patients with GNBi and GN tumors were 3.51 years (range, 0.96-14.85 years) and 4.80 years (range, 1.94-17.05 years), respectively. In contrast, patients with UH tumors generally were older when they were diagnosed, and with median ages of 2.99 years (range, 1.30-8.84 years) for patients with U subtype tumors, 2.59 years (range, 0.0-12.57 years) for patients with PD subtype tumors, 2.16 years (range, 0.35-9.90) for patients with D subtype tumors, and 3.26 years (range, 0.57-15.90 years) for patients with GNBn tumors. CONCLUSIONS: This study confirmed the prognostic significance of the International Classification, substantiated age-linked prognostic effects of the morphologic indicators for patients with the tumors in the NB category, and supported the concept of an age-appropriate framework of maturation for patients with the tumors in the FH group.

Adolescent↗
PubMed2000

Histopathology defines prognostic subsets of ganglioneuroblastoma, nodular.

BACKGROUND: Ganglioneuroblastoma, nodular (GNBn) is a rare subtype of the family of neuroblastic tumors (neuroblastoma, ganglioneuroblastoma, and ganglioneuroma) that are classified in the unfavorable histology group according to the International Neuroblastoma Pathology Classification (Shimada system). Tumors of this subtype have been considered to represent a prototypic example of biologically and clinically nonaggressive (Schwannian stroma-rich and stroma-dominant) components combined with biologically and clinically aggressive nodular (Schwannian stroma-poor) components. However, detailed histopathologic analysis as well as thorough prognostic evaluation of patients with this subtype has not been reported. METHODS: Pathology slides and reports from a total of 70 GNBn patients from the Children's Cancer Group (CCG)-3881 and CCG-3891 studies were reviewed. Sixty-eight tumors were classified in the favorable subset (FS) or the unfavorable subset (US) based on the evaluation of nodular components by applying the same histopathologic criteria (patient age, grade of neuroblastic differentiation, mitosis-karyorrhexis index) that are used for neuroblastomas in the International Neuroblastoma Pathology Classification. Patient prognosis as well as clinical and biologic characteristics within the subsets were analyzed, and the results were compared with those from 654 non-GNBn patients who were enrolled in the same CCG studies during the same period. RESULTS: Patients with GNBn tumors, usually diagnosed at age > 1 year, had a significantly lower overall 5-year event free survival (EFS) rate than patients with non-GNBn subtypes (44.7% EFS vs. 65.0% EFS; P = 0. 0073). A significant difference in the outcome of the patients between the FS (22 patients; 86.1% EFS; 95.0% survival rate) and the US (46 patients; 29.0% EFS; 40.7% survival rate) of the GNBn subtype (P < 0.0005) was shown. When the cohort of patients with GNBn tumors was subdivided into FS and US, the outcomes were similar to those of patients with tumors of favorable histology (397 patients; 90.5% EFS; 97.6% survival rate) and with tumors of unfavorable histology (257 patients; 27.0% EFS; 35.7% survival rate) of the non-GNBn type. The patients with US tumors frequently (63.0%) presented with distant metastasis. CONCLUSIONS: The current study demonstrates that the nodular components in GNBn tumors are not always aggressive. The prognosis of these patients can be determined by the analysis of age-linked histopathologic features.

Age Factors↗
PubMed2000

The biomechanical effect of postoperative hypolordosis in instrumented lumbar fusion on instrumented and adjacent spinal segments.

STUDY DESIGN: Change in lumbar lordosis was measured in patients that had undergone posterolateral lumbar fusions using transpedicular instrumentation. The biomechanical effects of postoperative lumbar malalignment were measured in cadaveric specimens. OBJECTIVES: To determine the extent of postoperative lumbar sagittal malalignment caused by an intraoperative kneeling position with 90 degrees of hip and knee flexion, and to assess its effect on the mechanical loading of the instrumented and adjacent segments. SUMMARY OF BACKGROUND DATA: The importance of maintaining the baseline lumbar lordosis after surgery has been stressed in the literature. However, there are few objective data to evaluate whether postoperative hypolordosis in the instrumented segments can increase the likelihood of junctional breakdown. METHODS: Segmental lordosis was measured on preoperative standing, intraoperative prone, and postoperative standing radiographs. In human cadaveric spines, a lordosis loss of up to 8 degrees was created across L4-S1 using calibrated transpedicular devices. Specimens were tested in extension and under axial loading in the upright posture. RESULTS: In patients who underwent L4-S1 fusions, the lordosis within the fusion decreased by 10 degrees intraoperatively and after surgery. Postoperative lordosis in the proximal (L2-L3 and L3-L4) segments increased by 2 degrees each, as compared with the preoperative measures. Hypolordosis in the instrumented segments increased the load across the posterior transpedicular devices, the posterior shear force, and the lamina strain at the adjacent level. CONCLUSIONS: Hypolordosis in the instrumented segments caused increased loading of the posterior column of the adjacent segments. These biomechanical effects may explain the degenerative changes at the junctional level that have been observed as long-term consequences of lumbar fusion.

Adult↗
PubMed1997

A constitutive modeling of the human lumbar intervertebral disc and forward-backward bending simulation.

This paper presents a constitutive law of the lumbar intervertebral disc to be described mathematically with the finite deformation theory. Mechanical behavior of the cadaveric lumbar disc obtained from continuous cyclic compression-tension tests and continuous cyclic axial torsion tests was formulated by the constitutive equation with a semi-circular shaped model. These equations were formulated with or without taking the nucleus pulposus into account. It was also confirmed that forward-backward bending behavior of the disc could be simulated numerically from these equations.

Biomechanical Phenomena↗
PubMed1996

Effects of degeneration on the elastic modulus distribution in the lumbar intervertebral disc.

STUDY DESIGN: Local elastic moduli of sliced intervertebral disc specimens were studied after establishing the relation between the elastic modulus and indentation behaviors by model tests using polyurethane specimens. OBJECTIVES: This study presents a method to quantify the distribution of compressive elastic moduli in the lumbar intervertebral disc and to clarify the effects of degeneration on the distribution. SUMMARY OF BACKGROUND DATA: No study has been performed to evaluate the distribution of axial compressive elastic moduli, which is supposed to relate previous biomechanical, biological, and biochemical findings regarding the intervertebral disc. METHODS: Local compressive elastic moduli of the intervertebral disc were estimated by indentation tests. To evaluate the distribution of elastic moduli, indentation tests were performed at nodal points of a 10 mm x 10 mm network on a specimen. Nine cadaveric lumbar discs (L3-L4 and L4-L5) with various degrees of degeneration were tested. The age of subjects ranged 39 to 90 years (mean, 58.4 years). RESULTS: The distribution of elastic moduli in normal discs was symmetric about the midsagittal plane. The mean elastic modulus in the nucleus pulposus was 5.8 kPa and those of the anterior and posterior anulus fibrosus were 110.7 and 75.8 kPa, respectively. The elastic moduli in the lateral portions were the lowest in the normal anulus, and were close to the values of the nucleus. Compared to normal discs, degenerated discs showed irregular distributions of elastic moduli. The elastic moduli of the degenerated nucleus were higher than those in normal discs. CONCLUSIONS: The distribution of elastic moduli is much different between discs with and without degeneration.

Adult↗
PubMed1992

The mechanical properties of the human L4-5 functional spinal unit during cyclic loading. The structural effects of the posterior elements.

Cyclic axial compression-tension tests and cyclic torsional tests were performed on ten fresh human L4-5 functional spinal units to investigate the structural effects of the posterior elements on the mechanical properties of L4-5 functional spinal units. The stiffness of the functional spinal unit increased with the increase of displacement under every loading. This was same in the intact functional spinal units and the functional spinal units after removal of each posterior element, respectively. All the posterior elements contributed to the compressive, tensile, and torsional stiffness of L4-5 functional spinal units. The apophyseal joints had a significant effect on the compressive and torsional stiffness. The effect of the apophyseal joints on the torsional stiffness became greater according to the extent of displacement, whereas their effect on the compressive stiffness was constant. The posterior ligaments (supraspinous and interspinous ligaments) had a significant effect on the tensile stiffness.

Adult↗
PubMed1988

Establishment and characterization of a human cell strain, KT, with high sensitivity to UV-killing and to cell proliferation inhibition by interferon.

We have established a human cell line, designated KT, with high susceptibility to both cell proliferation inhibition by interferon and UV-killing, from a metastatic breast carcinoma. A tumor marker, a pregnancy-specific glycoprotein (Schwangerschaftsprotein 1; SP1), and carcinoma characteristics compatible with ductal carcinoma of the breast were seen in KT cells by electron microscopic observation. KT cells were slightly more resistant to X-ray-induced toxicity than fibroblastic cells, termed KS, from the scalp of the patient. But, KT cells had lower cloning efficiency after UV irradiation than did KS cells: D0 values of 1.5 J/m2 and 7.2 J/m2, respectively. KT cells also appeared more susceptible to human interferon (HuIFN) preparations (alpha, beta, gamma and natural or recombinant) than did KS cells, as measured by cell colony formation ability, proliferation rates, and [3H]deoxythymidine incorporation levels into acid-insoluble cell materials. The sensitivity of KT cells to UV and HuIFN was greater than that of human RSa cells, a cell line with high sensitivity to both agents. KT cells had more capacity for UV-induced DNA-repair replication synthesis than did RSa cells, the capacity being much the same as that of KS cells. There was no significant difference in levels of antiviral activity induced by HuIFN and binding capacity for 125I-labeled IFN-alpha A between KT and KS cells. KT cells appeared refractory to cell proliferation inhibition by tumor necrosis factor (TNF) preparations.

Brain Neoplasms↗
PubMed1982

[Two cases of central nervous system leukemia which responded excellently to intra-arterial injection of ACNU].

Local chemotherapy by intra-arterial administration of ACNU was performed in 2 cases with CNS leukemia, which responded well to this therapy. The first patient was a 42-year-old male who was diagnosed as having chronic myelogenous leukemia with local infiltration of leukemic cells to the optic nerves. By intra-arterial infusion of ACNU (60mg), symptoms and results of ophthalomological examinations were improved remarkably. The second case was a 16-year-old male diagnosed as having acute lymphoblastic leukemia, and complicating with meningeal involvement during the course of chemotherapy. Complete remission was achieved by intra-thecal administration ACNU. Intra-arterial infusion of ACNU would be an effective local chemotherapy of CNS leukemia and its effectiveness could be achieved by less dose of ACNU compared to that of intravenous infusion. Therefore, side effects, e.g., delayed myelosuppression caused by ACNU could be decreased by this method.

Adolescent↗
PubMed1980

[Pharmacological properties of trapidil: comparison with other coronary vasodilators (author's transl)].

Effects of trapidil and other coronary vasodilators on retrograde blood flow in acute coronary-ligated dogs, isolated large and small coronary arteries of pig, platelet aggregation, biosynthesis of prostacyclin in isolated aortic rings and hyperlipemia in quails were investigated. Trapidil showed an increase in retrograde blood flow while dipyridamole, nifedipine, diltiazem and dilazep did not. Trapidil and nitroglycerin relaxed large coronary arteries, while dipyridamole, diltiazem, dilazep and adenosine relaxed small arteries. Trapidil, dipyridamole, diltiazem and aspirin protected against the secondary phase of ADP-induced platelet aggregation in guinea-pig platelet rich plasma more effectively than did nifedipine and dilazep. Trapidil and aspirin protected only against rabbit platelet aggregation as induced by arachidonic acid. Moreover, only trapidil protected against platelet aggregation as induced by prostaglandin G2-thromboxane A2 mixture. Trapidil and dipyridamole enhanced the platelet aggregation protection of prostacyclin. Trapidil also facilitated biosynthesis of prostacyclin more markedly than did the other drugs. Trapidil increased serum content of HDL cholesterol and significantly lowered serum content of triglyceride and the ratio of LDL cholesterol to HDL cholesterol in hyperlipemic quails. Dipyridamole, diltiazem, nifedipine and dilazep, however, showed little effect.

Animals↗