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Biomedical subjects

S Nakazawa

Publications and source records attributed to S Nakazawa.

At least 127 records · Page 7Linked to original sources

Molecular analysis of minimally differentiated acute myeloid leukemia with chromosome 16 inversion.

We report a 3-year-old girl with minimally differentiated acute myeloid leukemia and chromosome 16 inversion (inv 16). Inv 16 is generally associated with acute myelomonocytic leukemia with dysplastic eosinophils in the bone marrow (AML-M4Eo). Recently, molecular analysis showed that a fusion gene is generated by this inversion between the CBFB gene on the q arm and the MYH11 gene on the p arm. Using reverse transcriptase-polymerase chain reaction analysis, we tried to detect CBFB/MYH11 chimeric mRNA in blasts from our patients, however, were unable to detect any chimeric mRNA in the blasts: The absence of CBFB/MYH11 transcripts in this case suggests that rare chimeric products might be formed as a result of inv 16 that could not be detected by the primer sets used in this study. Another possibility is that different genes are rearranged on the chromosome 16 with the inv 16. More detailed molecular analysis of this case might be necessary in order to elucidate these possibility. Analyzing leukemias with inv 16 which do not have a typical CBFB/MYH11 chimeric mRNA might lead to understanding an alternative pathogenesis for acute leukemia with inv 16.

Acute Disease↗

[Efficacy and side effects of lidocaine by intravenous drip infusion in children with intractable seizures].

Intravenous drip infusions of lidocaine (IDIL; 1-5 mg/kg/h) were performed in ten patients with intractable seizures. The medication was very effective in five patients, whose seizures disappeared immediately after the treatment of IDIL. In four patients, the medication proved to be effective judging from decreased incidence of seizures. In one patient with intractable seizures, the therapy was not effective. In nine patients with the effective medication, five had generalized seizures and four had partial seizures. Side effects were observed in four patients. Two patients had muscle hypotonia, one had visual and auditory hallucination and another had bradycardia. These symptoms completely disappeared after the ceasing of IDIL. Serum concentrations of lidocaine at the appearance of the side effects ranged from 1.8 to 4.7 micrograms/ml, although the toxicity level is more than 5.0 micrograms/ml for arrhythmic adult patients. These findings suggest that the serum toxic level of lidocaine in children is different from that in adults, and that careful observation and appropriate management for the children with lidocaine therapy should be necessary, even though the serum level of lidocaine ranges within the therapeutic level.

Adolescent↗

[Cerebral cortical dysplasia associated with epilepsy: MRI and clinical aspects].

Clinical and electroencephalographic (EEG) studies were performed in nine patients with cerebral cortical dysplasia (CD). Interictal single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propylene amine oxime were studied in four patients. A patient with hemimegalencephaly and agyria had poor outcome in both developmental and epileptic aspects. The prognoses of clinical seizures were generally related to the severity, location and size of CD. The size of the lesion was not always correlated with the clinical seizure outcome. Four patients had focal pachygyria. Clinical pictures were diverse in these patients. One patient underwent callosotomy for the control of intractable seizures. The others had no clinical seizures despite of the appearance of paradoxical discharges in the area of pachygyria. The distribution of CD detected by MRI did not always correlate with that of paradoxical discharges in EEG and/or hypoperfusional areas seen in SPECT. These findings suggest that a detailed neuroimaging study is useful to elucidate the epileptogenesis in patients with CD, and that all the cortical abnormalities in patients with intractable epilepsy are not detected by MRI.

Adolescent↗

[The studies of extracorporeal shock wave lithotripsy (ESWL) for pancreatic ductal stones].

30 patients with main pancreatic duct stones were treated by ESWL. In 18 of 22 patients who had not previously undergone endoscopic pancreatic sphincterotomy (EPST) or endoscopic sphincterotomy (EST), the stone fragments disappeared after ESWL. The fragments were removed endoscopically in the remaining 4 cases. Complete clearance was achieved in 8 cases with endoscopically unextractable stones by ESWL. After the ESWL procedure, absolute relief from pain was reported by in 19 of 22 patients with abdominal complaints. Serum amylase levels decreased significantly, and dilatation of the main pancreatic duct (MPD) was reduced. In the medium-term follow-up period, pancreatic exocrine function and endocrine function had a possibility to be preserved. One case of pancreatic cancer and one case of an intraductal papillary tumor of the pancreas were found, indicating that careful observation is necessary even after complete removal of pancreatic stones. In cases of Santorini duct dominant, multiple stones, or stricture of the MPD, ESWL should be combined with EPST and endoscopic stenting for preventing recurrence of acute pancreatitis and pancreatic stones. In conclusion, ESWL is the first choice of treatment for pancreatolithiasis and useful procedure and the limited complications.

Adult↗

[Cord blood stem cell transplantation for infantile acute lymphoblastic leukemia after primary cytomegalovirus infection].

We report a 1-year-old boy with infantile lymphoblastic leukemia in first complete remission who received a cord blood stem cell transplantation (CBSCT) from an HLA identical sibling. We collected 120 ml of cord blood when his brother was born, which contained 4.2 x 10(8) mononuclear cells (4.2 x 10(7)/kg) and 3.1 x 10(5) CFU-GM (3.1 x 10(4)/kg). One month prior to transplantation, he showed persistent fever and liver dysfunction, and was finally diagnosed as having primary cytomegalovirus (CMV) infection which was demonstrated by elevation of serum anti-CMV-IgM. The administration of ganciclovir dramatically improved the clinical symptoms and abnormal laboratory findings, and was continued up to 1 month after transplantation to suppress the CMV reactivation. The preconditioning regimen consisted of busulfan (16 mg/kg/4 days) and cyclophosphamide (120 mg/kg/2 days), and cyclosporin A (CyA) alone was used for graft-versus-host disease (GVHD) prophylaxis. Fever suspicious of grade I GVHD developed on day 19, but subsided by increasing the dose of CyA. The WBC and platelet counts reached greater than 1,000/microliter and 50 x 10(3)/microliter on days 12 and 42, respectively. It is now at 13 months since transplantation, and he remains in a disease free state.

Antiviral Agents↗

Clinicopathologic features of small pancreatic adenocarcinoma. A collective study.

BACKGROUND: Early diagnosis and complete removal of pancreatic adenocarcinoma (PC) is essential to improve its poor prognosis. It is necessary to find PC when it is small and at an early stage if surgical treatment is to be successful. This is an investigation of the clinicopathologic features of small PC. METHODS: Thirty-one resected and histopathologically examined cases of small PC, 2 cm or less in greatest dimension, were collected from 7 institutions between 1989 and 1994, and their clinicopathologic features were analyzed in detail. RESULTS: Eighteen patients (58.1%) had some symptoms or signs at the time of diagnosis, however, the other 13 (41.9%) had no symptoms. There was no sensitive blood test for the detection of small PC. The detection rates of the pancreatic tumor mass on ultrasonography, endoscopic ultrasonography, and computed tomography were 64.5% (20/31), 73.7% (14/19), and 64.5% (20/31), respectively. Only 13 patients (41.9%) were in International Union Against Cancer (UICC) Stage I, and the other 18 were in Stage III or IV due to lymph node metastasis or peritoneal dissemination. The overall 4-year postoperative survival rate was 54.5% and that of patients in Stage I was 77.9%. CONCLUSIONS: To detect a small PC, a thorough examination may be required in patients with slightly abnormal findings on laboratory tests or imaging modalities, even if the patient is asymptomatic. PC 2 cm or less and belonging to Stage I may be regarded as an early carcinoma, because of its good prognosis.

Adenocarcinoma↗

Prolonged and extensive IgG immunoreactivity after severe fluid-percussion injury in rat brain.

The relationships between protein extravasation, morphological changes in neurons, and reactive changes in axons were evaluated in rats subjected to right lateral fluid-percussion injury to the brain (4.8-5.6 atm, 20 ms). Serial sections of the brain were immunostained with antibodies to rat immunoglobulin G (IgG) and 68-kDa neurofilament at 1 h to 2 weeks after injury or sham injury. Ischemic changes in neurons were noted in the injured cortex at 6-48 h after injury, and macroscopic hemorrhages were noted in the right corpus callosum and external capsule at 1 h to 1 week after injury. Extracellular IgG immunostaining was observed in the right cortex and right hippocampus at 1 h to 1 week after injury, and in the cortices and hippocampi bilaterally at 2 weeks after injury, but was most prominent in those regions at 24 h after injury. Intracellular IgG staining was noted in the neurons of cortices, hippocampi, brainstem, and cerebellum at 1 h to 2 weeks after injury. The number of IgG immunoreactive neurons was greatest at 1 week after injury. Thickened IgG immunoreactive axons and reactive axonal changes seen with neurofilament immunostaining were both in the similar region of the brainstem at 1 h to 1 week after injury. It appears that prolonged and widespread breakdown of the blood-brain barrier to plasma protein occurs after severe concussive brain injury and that this breakdown is not always accompanied by morphological changes. Intra-axonal IgG immunostaining provides additional clues to the pathogenesis of axonal damage following diffuse brain injury.

Animals↗

Immunolocalization of cellular glutathione peroxidase in adult rat lungs and quantitative analysis after postembedding immunogold labeling.

To determine the distribution of cellular glutathione peroxidase in rat lungs, the tissues were stained immunohistochemically. Quantitative analysis was performed in certain cell types of alveolar linings, after the ultrathin sections were stained by a postembedding immunogold technique. Immunoblot analysis revealed that homogenates of rat liver, heart, and lungs all gave a single band. Under the light microscope, the following tissues were stained intensely: epithelial cells, smooth muscle cells and glands of bronchi and bronchioles, type II alveolar cells, and alveolar macrophages. Under immunoelectron microscopy, type II alveolar cells and macrophages were abundant in mitochondria. The mitochondria, nucleus, and cytoplasm of macrophages were labeled almost twice as densely as the respective compartments of type II alveolar cells. Within cell types, the mitochondria were labeled twice as densely as the nuclei. The other particles were less than half as densely labeled as the nuclei. The labeling was slightly less dense in the cytoplasm than in the nucleus. The present study revealed that glutathione peroxidase occurred predominantly in the epithelial linings and metabolically active sites in rat lungs. The tissues that were previously found to be rich in superoxide dismutases were also rich in glutathione peroxidase.

Animals↗

Immunohistochemical localization and quantitative analysis of cellular glutathione peroxidase in foetal and neonatal rat tissues: fluorescence microscopy image analysis.

To quantitate the developmental changes in selenium-dependent cellular glutathione peroxidase during the perinatal period, tissue sections from foetal (day 12 to day 22) and neonatal (day 6) rats were stained immunohistochemically using specific polyclonal antiserum. The intensity of the staining was quantified by fluorescence microscopy image analysis. There was a general trend of enriched glutathione peroxidase in the epithelial linings and metabolically active sites. Significant fluorescence was detected in cardiomyocytes, hepatocytes, renal tubular epithelium, bronchiolar epithelium and intestinal epithelium at day 15. The intensity increased in a stepwise manner thereafter. The overall increase in the intensity of staining in the heart, liver, kidneys, lungs and intestine was 1.5-, 2.3-, 1.6-, 1.7- and 3.0-fold, respectively. The phase of most rapid increase occurred during the foetal period in the liver, intestine and heart. In the kidneys and lungs, glutathione peroxidase increased significantly during foetal life, and to a similar extent postnatally. These results suggest that the intracellular H2O2-scavenging system develops during the foetal period as an essential mechanism for living under atmospheric oxygen conditions. The late development observed in the kidneys and lungs is consistent with the relative biological immaturity of these organs in full-term neonates.

Animals↗

Pneumatosis intestinalis and necrotizing enterocolitis associated with liver cirrhosis.

We report a 58-year-old woman with pneumatosis intestinalis and necrotizing enterocolitis associated with liver cirrhosis. She was receiving treatment for liver cirrhosis and hepatic failure when sudden severe right upper abdominal pain and fever developed. Abdominal radiograph disclosed pneumatosis intestinalis, involving the ascending colon, and small collections of free air along the right hemidiaphragm. The pneumatosis intestinalis appeared in both cystic and linear form. Autopsy revealed necrosis and multiple gas-filled mural cysts in the ascending colon. To our knowledge, this is the first case to be reported of pneumatosis intestinalis and necrotizing enterocolitis associated with liver cirrhosis.

Colon↗

Long-term outcome of patients who received Starr-Edwards valves between 1965 and 1977.

To determine the risk factors relating to long-term outcomes of the Starr-Edwards ball valve, data from 150 patients (75 males, 75 females; age range 9-67 years); who underwent valve replacement (44 aortic, 106 mitral) between 1965 and 1977 at Niigata University were reviewed retrospectively. Valve models 6120/6320 and 1260/2320 were mainly used in mitral and aortic positions, respectively. The cumulative follow-up period was 2227.4 patient-years. Using the Kaplan-Meier life-table method, actuarial probability of freedom from valve-related mortality, morbidity and thromboembolism were analysed. Thirteen patients died from various causes during hospitalization. Some 80 patients suffered 97 instances of valve-related morbidity and 58 died during follow-up (up to 28 years). Patient age > 50 years affected the actuarial probability of freedom from valve-related mortality in the entire group (P < 0.05). Valve type and the year of operation were discriminative predictors of thromboembolic complications in the entire group (both P < 0.05) and in the mitral valve replacement group (P < 0.01 and P < 0.001). However, only the year of operation affected the actuarial probability of freedom from all valve-related morbidity in the entire group and in the mitral valve replacement group (both P < 0.05). Univariate analysis revealed that age at surgery, valve type, and the year of operation were related to late postoperative outcome in patients who received a Starr-Edwards ball valve between 1965 and 1977.

Actuarial Analysis↗

Cellular differentiation and development of pyloric mucosal metaplasia in the human gall-bladder.

The development of pyloric mucosal metaplasia (PMM) with regard to cellular differentiation in the human gallbladder was studied by mucin staining (paradoxical concanavalin A (Con A), galactose oxidase-Schiff (GOS) and alcian blue (pH 2.5) PAS (AB-PAS) and immunohistochemistry (pepsinogen II (PgII) and SH-9, and proliferating cell nuclear antigen (PCNA). PMM was divided into three stages of development by three-dimensional (3D) computer graphic reconstruction analysis. In the early stage, a transitional zone of PCNA positive cells was observed between areas of SH-9 and/or GOS reactive cells and class III and/or Pg II positive cells in flat monolayered epithelium. In the middle stage, shallow pits became apparent as areas enlarged, with these becoming deeper in the advanced stage, whereby SH-9 and/or GOS reactive cells and class III and/or Pg II positive cells were observed at the upper and lower portion of the pits, respectively, with PCNA-positive cells forming a narrow zone between the two cell populations. Consequently, the structure of PMM gradually resembles that of the normal gastric pyloric mucosa.

Cell Differentiation↗

Increased activity of plasma cholesteryl ester transfer protein in children with end-stage renal disease receiving continuous ambulatory peritoneal dialysis.

The activity of cholesteryl ester transfer protein (CETP) was assayed in sera of children and adolescents on continuous ambulatory peritoneal dialysis (CAPD) by coincubating lipoprotein-deficient samples with exogenous donor and acceptor lipoproteins. Serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B and apolipoprotein B/apolipoprotein A1 ratio were increased, while the high-density lipoprotein cholesterol level was decreased. The CETP activity in children on CAPD exceeded that in either adults or control children, and was correlated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol, and apolipoprotein B/apolipoprotein A1 ratios. The CETP activity in CAPD patients may be due to increased synthesis in response to a protein loss in the dialysis fluid and may exacerbate atherosclerosis.

Adolescent↗

Right ventricular systolic performance before and after surgery for tricuspid regurgitation associated with mitral stenosis.

The reversibility of right ventricular function in patients with mitral stenosis associated with secondary tricuspid regurgitation (TR) is as yet undetermined. We assessed the right ventricular systolic performance by cardiac catheterization before and 19 months after surgery in 18 patients who underwent DeVega's tricuspid annuloplasty plus mitral valve replacement (MS plus TR group) and in 9 with mitral valve replacement for isolated mitral stenosis (MS group). After surgery, the right ventricular systolic pressure decreased significantly in both groups (both p < 0.01). In the MS plus TR group, the postoperative right ventricular end-diastolic and end-systolic volume indices (RVEDVI and RVESVI, respectively) were significantly decreased compared with the respective preoperative values (both p < 0.001). No significant difference was noted between the groups with regard to the right ventricular peak-systolic pressure/end-systolic volume index ratio (RVPSP/ESVI) either before or after surgery. Various left ventricular indices were comparable between the groups both before and after surgery. Linear regression analysis revealed significant correlations between RVEDVI and the RVPSP/ESVI, and between RVPSP and the RVPSP/ESVI both before and after surgery. These results indicate that right ventricular systolic performance in patients with MS plus secondary TR became comparable to those that in patients with isolated MS after surgery, and that this was probably due to nearly equivalent right ventricular contractility before surgery.

Adult↗

Multi-organ erythrocyte sequestration and ligand expression in rhesus monkeys infected with Plasmodium coatneyi malaria.

The pathogenesis of human cerebral malaria is suspected to be caused by blockage of cerebral microvessels by the sequestration of parasitized human red blood cells (PRBC). Examination of infected tissues indicate PRBC sequestration in microvessels is the result of PRBC knob attachment to endothelial cell surface cytoadherence receptors such as CD36, thrombospondin (TSP), and intercellular adhesion molecule-1 (ICAM-1). In lieu of fresh human tissue, several animal models for human cerebral malaria have been developed, the Plasmodium coatneyi-infected rhesus monkey model being the most versatile. To further the understanding of noncerebral malarial complications during disease, we examined noncerebral tissues of infected rhesus monkeys. Our study demonstrated similar microvessel PRBC sequestration and the presence of cytoadherence ligands in noncerebral tissues. Immunohistochemical analysis showed CD36, TSP, and ICAM-1 cytoadherence proteins in several major organs.

Animals↗

Mechanisms of glucocorticoid resistance in human leukemic cells: implication of abnormal 90 and 70 kDa heat shock proteins.

The unliganded glucocorticoid receptor is a multi-oligomer complex consisting of a ligand-binding protein with which two 90 kDa heat shock proteins (hsp90s) are associated. Upon binding of glucocorticoid to the receptor, the ligand-binding protein, which dissociated from hsp90s, enters the nucleus, binds to a specific site in DNA, and thus transmits signal(s). The 70 kDa heat shock protein (hsp70) also works as a molecular chaperone when the ligand-binding protein enters the nucleus. Regarding the mechanisms of glucocorticoid resistance, a decreased expression of glucocorticoid receptor and a mutant protein with low ligand binding affinity have been reported. In the present study, to address other mechanisms of glucocorticoid resistance, we examined the expression of hsp90 and hsp70 in addition to the number of glucocorticoid-binding sites and their affinity using glucocorticoid-sensitive and -resistant human leukemic cell lines. We showed that two of nine resistant cell lines with normal glucocorticoid-binding proteins express aberrant hsp90 and extremely low hsp70, while another seven resistant cell lines had decreased binding sites with normal hsps. These results suggest that there are at least two independent mechanisms of glucocorticoid resistance in human leukemic cell lines: the decreased ligand-binding sites and the abnormal hsps expression.

Antineoplastic Agents, Hormonal↗

[A successful treatment with a continuous intravenous lidocaine for a cluster of minor seizures in a patient with Doose syndrome].

We reported a 7-year-old girl with myoclonic-astatic epilepsy of early childhood (Doose syndrome). She had minor seizures (i. e. absence, atonic and myoclonic seizures) refractory to treatment with many kinds of anti-epileptic drugs as well as thyrotropin releasing hormone. Though she had suffered from long-lasting clusters of minor seizures, the treatment with continuous intravenous lidocaine successfully brought a case of prolonged remission of both clinical seizures and EEG abnormalities. It has been reported that lidocaine is effective mainly for partial seizures. The efficacy of lidocaine for generalize seizures, however, has been reported only in a few papers. We considered that the treatment with continuous intravenous lidocaine is indicated in patients with Doose syndrome presenting with a cluster of refractory minor seizures.

Child↗