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Biomedical subjects

S Nakao

Publications and source records attributed to S Nakao.

At least 127 records · Page 7Linked to original sources
PubMed1998

CD4(+) cytotoxic T-cell clones specific for bcr-abl b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner.

Although it is well known that CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the suppression of cancer cell growth, the significance of CD4(+) CTLs in resistance to cancer is obscure. In an attempt to elucidate the role of CD4(+) CTLs in immunosurveillance of chronic myelogenous leukemia (CML), we examined the immunologic functions of bcr-abl b3a2 fusion peptide-specific CD4(+) CTL clones. Seven CD4(+) T-cell clones that responded to stimulation with b3a2 peptide, but not with b2a2 peptide or physiological counterparts bcr b3b4 and abl 1A-a2 peptides, were established from two healthy individuals. Restriction elements of these clones were HLA-DRB1*0901. These CD4(+) T-cell clones exhibited b3a2 peptide-specific and HLA-DRB1*0901-restricted cytotoxicity and produced interleukin-3 (IL-3), IL-4, IL-10, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor in response to bcr-abl peptide stimulation, indicating they were Th0 clones. The numbers of HLA-DRB1*0901-positive b3a2, but not those of b2a2-positive or HLA-DRB1*0901-negative CML cell colonies increased when CML cells were cultured with b3a2-specific CD4(+) CTL clones. These data suggest that bcr-abl-specific CD4(+) CTLs recognize CML cells in an antigen-specific and HLA-DR-restricted manner, and that they do not inhibit, but in fact augment, CML cell growth.

Amino Acid Sequence↗
PubMed1998

Patients with familial hypertrophic cardiomyopathy caused by a Phe110Ile missense mutation in the cardiac troponin T gene have variable cardiac morphologies and a favorable prognosis.

BACKGROUND: Mutations that cause familial hypertrophic cardiomyopathy have been identified in several genes that encode contractile proteins. Patients with mutations in the cardiac troponin T (cTnT) gene have particularly poor prognosis but only mild hypertrophy. To date, no benign mutation in the cTnT gene has been reported. The clinical characteristics and prognosis of patients with the Phe110Ile mutation in the cTnT gene is unclear because few affected individuals have been identified. METHODS AND RESULTS: Forty-six probands with familial hypertrophic cardiomyopathy were screened for mutations in the cTnT gene. The Phe110Ile missense mutation was found in 6 probands. Individuals in the 6 families were analyzed genetically and clinically. Haplotype analysis was performed with markers encompassing the cTnT gene. Left ventricular hypertrophy was classified as type I, II, III, or IV according to the criteria of Maron et al. The Phe110Ile mutation in the cTnT gene was identified in 16 individuals. Two of the 6 families shared the same flanking haplotype, and 4 were different from each other. Affected individuals exhibited different cardiac morphologies: 4 had type II, 6 had type III, and 3 had type IV hypertrophy with apical involvement. Three individuals with the disease-causing mutation did not fulfill clinical criteria for the disease. The product-limit survival curve analysis demonstrated a favorable prognosis. CONCLUSIONS: Multiple independent mutations of residue 340 in the cTnT gene have been described, suggesting that this may be a "hot spot" for such events. The Phe110Ile substitution causes hypertrophic cardiomyopathy with variable cardiac morphologies and a favorable prognosis.

Adult↗
PubMed1998

Usefulness of adenosine triphosphate-atropine stress echocardiography for detecting coronary artery stenosis.

There have been few studies on adenosine triphosphate (AT) stress echocardiography. The AT stress test may have fewer adverse effects than the adenosine stress test. The addition of atropine to AT echocardiography may enhance the sensitivity for detection of coronary artery disease (CAD). The purpose of this study was to determine the utility of AT-atropine echocardiography for detection of CAD. The group studied consisted of 112 patients with suspected CAD. Sixty-one patients did not have a history of prior myocardial infarction (group I) and 51 patients did (group II). AT was infused intravenously at 180 microg/kg/min for 14 minutes. Atropine (0.25 mg intravenously, repeated up to maximum total dose of 1 mg) was administered starting after 8 minutes of AT infusion. Ischemic response was defined as new or worsening wall motion abnormality occurring during the infusion. The sensitivity and specificity for detection of CAD were assessed using the representative echocardiograms during single AT infusion and AT-atropine infusion. Sixty-two patients had CAD. Fifty-eight patients (52%) developed minor side effects that resolved promptly. The rate-pressure product (10(3)/mm Hg beats/min) was significantly increased at 12 minutes of infusion (12.4+/-3.2) compared with that at baseline (9.1+/-2.3) and that at 6 minutes of infusion (9.4+/-2.1). The sensitivity for detection of CAD was 45% for AT echocardiography and 74% for AT-atropine echocardiography. The specificity was 94% for AT echocardiography and 90% for AT-atropine echocardiography. The sensitivity and specificity of AT-atropine echocardiography was 78% and 93%, respectively, in group I, and 70% and 86%, respectively, in group II. In conclusion, AT-atropine stress echocardiography seems to be well tolerated, safe, and useful for detection of CAD.

Adenosine Triphosphate↗
PubMed1998

A new criterion combining ST/HR slope and deltaST/deltaHR index for detection of coronary artery disease in patients on digoxin therapy.

We evaluated the clinical value of a new index combining deltaST/delta heart rate (HR) index and ST/HR slope for diagnosing coronary artery disease (CAD) in patients on digoxin therapy. Exercise treadmill tests were performed by 72 patients on digoxin therapy. Simple HR-adjusted indexes of ST-segment depression during exercise (deltaST/deltaHR index) and the decline calculated from the final 12 data points relating ST-segment depression to HR (ST/HR slope) were determined. A new index was obtained by subtracting the deltaST/deltaHR index from the ST/HR slope. On thallium scintigraphy, 37 of the 72 patients showed reversible perfusion defects related to the diseased coronary artery. The new index derived from this ST-HR relation was 4.1 +/- 3.6 microV/beats/min in the ischemic group and 1.3 +/- 1.0 microV/beats/min in the group of patients without ischemia (p <0.0001). An ST-HR relation > or = 1.5 was found in 33 of the 37 patients in the ischemic group, and in 7 of the 35 patients without ischemia (p <0.0001). The sensitivity of this criterion for prediction of myocardial ischemia was 89%, the specificity was 80%, and the predictive accuracy was 85%. Thus, this new ST-HR index is useful for detecting CAD in patients on digoxin therapy.

Aged↗
PubMed1998

Measurement of local cerebral blood flow by magnetic resonance imaging: in vivo autoradiographic strategy using 17O-labeled water.

Local cerebral blood flow (LCBF) was measured in cats by magnetic resonance imaging (MRI), using 17O-labeled water (H[2]17O) as a tracer. Cat brain images were obtained using a 256 x 240 matrix fast spin-echo sequence with a total acquisition time of 124 seconds per image. Intravenous injection of H(2)17O and sampling of arterial blood were simultaneously performed during the MRI scan. Injection of H(2)17O over 40 seconds caused a transient decrease in brain signal intensity, from which the changes in H(2)17O concentration of brain tissue were calculated. The concentration of H(2)17O in arterial blood was measured directly by 17O nuclear magnetic resonance (NMR) spectroscopy, and used as an input function for the calculation of LCBF. LCBF was successfully determined using an in vivo autoradiographic strategy in a total of three cats. In one, LCBF measurements were also performed under hypercapnic conditions, and LCBF maps of the cat brain during normocapnia and hypercapnia were constructed. These LCBF maps reflected well the changes in LCBF induced by hypercapnia, which indicated the validity of the used method.

Animals↗
PubMed1998

Propionic acid stimulates superoxide generation in human neutrophils.

Short-chain carboxylic acids are the metabolic by-products of pathogenic anaerobic bacteria and are found at sites of infection in millimolar quantities. We previously reported that propionic acid, one of the short-chain carboxylic acids, induces an increase in intracellular Ca2+ ([Ca2+]i) in human neutrophils. Here we investigate the effect of propionic acid on superoxide generation in human neutrophils. Propionic acid (10 mm) induced inositol 1,4, 5-trisphosphate (IP3) formation and a rapidly transient increase in [Ca2+]i, but not superoxide generation, whereas 1 microm formylmethionyl-leucyl-phenylalanine (fMLP), a widely used neutrophil-stimulating bacterial peptide, stimulated not only IP3 formation and Ca2+ mobilization but also superoxide generation. The IP3 level induced by propionic acid was slightly lower than that induced by fMLP. The transient increase in [Ca2+]i induced by propionic acid immediately returned to the basal level, whereas a sustained increase in [Ca2+]i, which was higher than the basal level, following a transient increase in [Ca2+]i was induced by fMLP. The peak level induced by propionic acid was lower than that with fMLP. In the absence of extracellular Ca2+, thapsigargin, a potent inhibitor of endoplasmic reticulum Ca2+-ATPase, induced an increase in [Ca2+]i even after propionic acid stimulation, but not after fMLP. The Ca2+ ionophore A23187 and thapsigargin induced superoxide generation by themselves. Propionic acid enhanced the superoxide generating effect of A23187 and thapsigargin. These results suggest that Ca2+ mobilization induced by propionic acid is much weaker than that with fMLP, and propionic acid is able to generate superoxide in the presence of a Ca2+ ionophore and a Ca2+ influx activator.

Adult↗
PubMed1998

Graft rejection and recovery of host-derived hematopoiesis after allogeneic bone marrow transplantation: relation to conditioning with high dose etoposide and total body irradiation.

Engraftment failure following allogeneic bone marrow transplantation (BMT) is rare in patients with acute leukemia, after frequent conditioning with marrow-lethal chemoradiotherapy. We evaluated the efficacy of a preparatory regimen consisting of fractionated total body irradiation (TBI) (12 Gy in six fractions) and high dose etoposide (60 mg/kg) administered as an 8-h infusion for allogeneic BMT in 16 consecutive patients with acute leukemia. Although 14 patients showed complete and sustained engraftment, the remaining two patients rejected bone marrow grafts from HLA-identical sibling donors and showed subsequent recovery of host-derived hematopoiesis. Despite the limited number of patients, this observation suggests that the immunosuppressive potential of etoposide may be inferior to that of cyclophosphamide (CY) and that etoposide as an alternative to CY as an antileukemic and immunosuppressive agent in allogeneic BMT may increase the risk of graft rejection.

Acute Disease↗
PubMed1998

Successful treatment of Epstein-Barr virus-associated natural killer cell large granular lymphocytic leukaemia using allogeneic peripheral blood stem cell transplantation.

We report a case of natural killer cell large granular lymphocytic (NK-LGL) leukaemia successfully treated with allogeneic peripheral blood stem cell transplantation (allo-PBSCT). The peripheral blood (PB) revealed an abnormal expansion of LGL that were CD3-, CD16- and CD56+, and had natural killer activity. In situ EBER-1 hybridization of the PB mononuclear cells showed the presence of Epstein-Barr virus (EBV) in the LGL as well as in lymphocytes infiltrating the tonsils and colon. Southern blotting with an EBV-terminal repetitive sequence probe demonstrated clonal proliferation of EBV+ cells. The patient received allo-PBSCT from his HLA-matched sister with a conditioning regimen involving the use of cyclophosphamide and fractionated total body irradiation. The patient promptly recovered trilineage haematopoiesis without graft-versus-host disease, and has been in complete remission without therapy for 10 months since allo-PBSCT, suggesting that allo-PBSCT could eradicate the NK-LGL leukaemic cells.

Adolescent↗
PubMed1998

The effect of varied doses of epinephrine on duration of lidocaine spinal anesthesia in the thoracic and lumbosacral dermatomes.

UNLABELLED: The efficacy of epinephrine in prolonging spinal analgesia has recently been confirmed in the lumbosacral but not in the thoracic, segments. Most previous studies used doses of epinephrine smaller than 0.3 mg. We studied the effects of 0.2, 0.4, or 0.6 mg of epinephrine added to hyperbaric lidocaine 60 mg in 7.5% dextrose solution for spinal anesthesia. Eighty patients were randomly divided into four groups: Group A received lidocaine without epinephrine, Group B received lidocaine plus 0.2 mL (0.2 mg) of epinephrine 1:1000 solution, Group C received lidocaine plus 0.4 mL (0.4 mg) of epinephrine, and Group D received lidocaine plus 0.6 mL (0.6 mg) of epinephrine. The maximal cephalad sensory level was between T2 and T3 for all groups. The median times for analgesia to regress two and four segments were significantly prolonged in Group D, but not in either Group B or C, compared with those in Group A. Times for regression to T12 and L3 were significantly prolonged in Groups B, C, and D compared with Group A. We conclude that the dose-dependent relationship of spinal analgesia can be applied to epinephrine, and that larger doses prolong lidocaine spinal anesthesia in the thoracic as well as the lumbosacral dermatomes. IMPLICATIONS: Prolongation of lidocaine spinal analgesia by intrathecal epinephrine is established in the lumbosacral, but not in the thoracic, dermatomes. Three doses of epinephrine--0.2, 0.4, and 0.6 mg--were compared. A dose-dependent response and significant prolongation with the 0.6-mg dose in the thoracic dermatomes were confirmed.

Adult↗
PubMed1998

Propofol inhibits ketamine-induced c-fos expression in the rat posterior cingulate cortex.

UNLABELLED: Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has psychotomimetic activity. NMDA receptor antagonists cause morphological damage in the posterior cingulate cortex, which may be the brain region responsible for their psychotomimetic effects. Benzodiazepines are effective in preventing these effects through gamma-aminobutyric acid A (GABA(A)) receptor activation. We investigated the effect of propofol, which has both GABAA receptor-activating and NMDA receptor-suppressing activity, on ketamine-induced c-fos expression in the rat posterior cingulate cortex. Propofol or vehicle was continuously infused IV. Fifteen minutes later, 100 mg/kg ketamine or isotonic sodium chloride solution was injected intraperitoneally. Two hours later, brain sections were prepared, and c-fos expression was detected using immunohistochemical methods. Propofol significantly inhibited ketamine-induced c-fos expression in the posterior cingulate cortex. Propofol itself did not induce c-fos expression in this brain region. We conclude that propofol may be able to inhibit ketamine-induced psychotomimetic activity and neuronal damage. IMPLICATIONS: In the present study, we demonstrated that the clinically relevant dose of propofol significantly inhibited ketamine-induced c-fos expression in the rat posterior cingulate cortex. This finding implies that propofol may inhibit ketamine-induced psychotomimetic activity and neuronal damage.

Anesthetics, Dissociative↗
PubMed1998

Supra- and extrasellar pituitary microadenoma as a cause of Cushing's disease.

There has been accumulating evidence that pituitary adenomas which cause Cushing's disease are located not only in sella turcica but also in various extrasellar and intracranial regions. We describe a case of Cushing's disease caused by a supra- and extrasellar ACTH-producing microadenoma, which originated in the anterior pituitary and extended upward without connecting to the stalk. The pituitary microadenoma was identified and removed by transsphenoidal microsurgery. After the surgery the patient experienced complete remission. This type of pituitary microadenoma is considered to be rare, but in order to accomplish successful surgical treatment, it is necessary to consider that pituitary adenomas which cause Cushing's disease may be located in such an unusual position.

Adenoma↗
PubMed1998

Allogeneic peripheral blood stem cell transplantation for standard-risk leukemia. A multicenter pilot study: Japanese experience. Japan Blood Cell Transplantation Study Group.

A multicenter phase II study of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) was conducted. Twenty-two patients (median age, 36 years) with standard-risk leukemia were transplanted with G-CSF-mobilized PBSC from an HLA-identical sibling donor, and received cyclosporine and methotrexate for GVHD prevention. Median days to ANC >500/microl and platelets >50,000/microl were 12 (9-20) and 16 (11-32), respectively. Grade II-IV acute GVHD developed in 6/21 (29%) and extensive chronic GVHD in 12/20 (60%). These observations indicate that allo-PBSCT is characterized by rapid hematologic engraftment, no increase of acute GVHD and an increased risk of chronic GVHD, and can be used as an alternative to allogeneic bone marrow transplantation.

Adolescent↗
PubMed1998

CD20-positive T-cell chronic lymphocytic leukaemia.

Although CD20 is considered to be a representative marker for B lymphocytes, the antigen is weakly expressed on a small subset of normal T lymphocytes. A 60-year-old man developed pancytopenia and hepatosplenomegaly due to clonal proliferation of atypical lymphocytes that were weakly positive for CD20. The leukaemic cells were also positive for T-cell antigens such as CD2, CD3, CD5, CD7, CD8 and T-cell receptor (TCR) Vbeta8 and for activation antigens such as CD38 and HLA-DR, but were negative for CD19, CD21, CD22, CD25. Southern blot analysis revealed rearrangement of the TCR-beta gene and a germline configuration of the immunoglobulin heavy chain gene. This is the first report of a case of clonal expansion of CD20dim T lymphocytes.

Antigens, CD20↗
PubMed1997

Mechanisms of limited maximum coronary flow in severe single-vessel coronary artery disease in humans due to vertical steal.

We evaluated the usefulness of a decrease in the average peak velocity from 4 to 10 minutes after infusion of dipyridamole for detecting myocardial ischemia in 50 patients, including patients with a prior myocardial infarction. The decrease in the average peak velocity from 4 to 10 minutes associated with vertical steal and combined with a coronary flow reserve of < 1.6 had a high predictive value for myocardial ischemia in patients with or without prior myocardial infarction.

Aged↗
PubMed1997

Unaltered secretion of beta-amyloid precursor protein in gelatinase A (matrix metalloproteinase 2)-deficient mice.

The beta-amyloid peptide, which forms extracellular cerebral deposits in Alzheimer's disease, is derived from a large membrane-spanning glycoprotein referred to as the beta-amyloid precursor protein (APP). The APP is normally cleaved within the beta-amyloid region by a putative proteinase (alpha-secretase) to generate large soluble amino-terminal derivatives of APP, and this event prevents the beta-amyloid peptide formation. It has been suggested that the gelatinase A (matrix metalloproteinase 2, a 72-kDa type IV collagenase) may act either as alpha-secretase or as beta-secretase. Mice devoid of gelatinase A generated by gene targeting develop normally, except for a subtle delay in their growth, thus providing a useful system to examine the role of gelatinase A in the cleavage and secretion of APP in vivo. We show here that APP is cleaved within the beta-amyloid region and secreted into the extracellular milieu of brain and cultured fibroblasts without gelatinase A activity. The data suggest that gelatinase A does not play an essential role in the generation and release of soluble derivatives of APP at physiological conditions.

Amyloid beta-Protein Precursor↗
PubMed1997

A new predictor of restenosis after successful percutaneous transluminal coronary angioplasty in patients with multivessel coronary artery disease.

With the goal of improving prediction of restenosis after percutaneous transluminal coronary angioplasty (PTCA) for multivessel coronary artery disease (CAD), we evaluated the usefulness of serial exercise treadmill tests. We previously reported that an increase in the deltaST/delta heart rate (HR) index at follow-up over the value obtained several days after PTCA was useful for detecting restenosis following PTCA for 1-vessel CAD. In that report, comparison of the deltaST/deltaHR index was made based on measurements from the lead disclosing the greatest ST displacement before PTCA. This method was not applicable to patients with multivessel CAD. Seventy-eight patients with multivessel CAD before and several days after PTCA and just before follow-up performed exercise treadmill tests. Simple HR-adjusted indexes of ST-segment depression during exercise (deltaST/deltaHR index) and the sum of the deltaST/deltaHR index in leads II, III, aVF, V4, V5, and V6 (sigma deltaST/deltaHR index) were determined. We compared the predictive power of an increase in sigma deltaST/deltaHR index at follow-up with that of a positive exercise treadmill test and a positive thallium scintigram for restenosis. At follow-up, 37 of the 78 patients showed restenosis. The sigma deltaST/deltaHR index had increased in 30 of these 37 patients (81%), and in 12 of the 41 patients (29%) without restenosis. An increase in sigma deltaST/deltaHR index had a significantly higher sensitivity than the other methods and a significantly higher specificity than a positive exercise treadmill test.

Aged↗
PubMed1997

Inhibition of immature erythroid progenitor cell proliferation by macrophage inflammatory protein-1alpha by interacting mainly with a C-C chemokine receptor, CCR1.

Several lines of evidence indicate that macrophage inflammatory protein-1alpha (MIP-1alpha) modulates the proliferation of hematopoietic progenitor cells, depending on their maturational stages. To clarify the mechanisms for the modulation of hematopoiesis by this chemokine, we examined the expression of a receptor for MIP-1alpha, CCR1, on bone marrow cells of normal individuals using a specific antibody and explored the effects of MIP-1alpha on in vitro erythropoiesis driven by stem cell factor (SCF) and erythropoietin (Epo). CCR1 was expressed on glycophorin A-positive erythroblasts in addition to lymphocytes and granulocytes. CCR1+ cells, isolated from bone marrow mononuclear cells (BMMNCs) using a cell sorter, comprised virtually all erythroid progenitor cells in the BMMNCs. Moreover, MIP-1alpha inhibited, in a dose-dependent manner, colony formation by burst-forming unit-erythroid (BFU-E), but not by colony forming unit-erythroid (CFU-E), in a methylcellulose culture of purified human CD34+ bone marrow cells. Although reverse-transcription polymerase chain reaction (RT-PCR) showed the presence of CCR1, CCR4, and CCR5 transcripts in CD34+ cells in BM, anti-CCR1 antibodies significantly abrogated the inhibitory effects of MIP-1alpha on BFU-E formation both in a methylcellulose culture and in a single cell proliferation assay of purified CD34+ cells. Although the contribution of CCR4 or CCR5 cannot be completely excluded, these results suggest that MIP-1alpha-mediated suppression of the proliferation of immature, but not mature erythroid progenitor cells, is largely mediated by CCR1 expressed on these progenitor cells.

Analysis of Variance↗