Search PubMed⌕ Search

Biomedical subjects

K Nagashima

Publications and source records attributed to K Nagashima.

At least 253 records · Page 14Linked to original sources

[A case of progressive multifocal leukoencephalopathy with methionine uptake demonstrated by PET].

We report here a 55-year-old man with progressive multifocal leukoencephalopathy (PML) associated with chronic adult T cell leukemia (ATL). Neurological examination revealed mild dementia, right homonymous hemianopsia and visual agnosia. Serologically anti-HTLV-I antibody was positive. Peripheral blood analysis showed ATL cells up to 23% in white blood cells. Because he did not have symptoms or signs directly related to ATL, it was considered that he had chronic ATL. T2-weighted cranial MRI demonstrated multiple hyperintensity lesions confined to the white matter from the bilateral occipital to parietal lobes, without enhancement after gadolinium administration or mass effect. We performed stereotactic biopsy of the left occipitoparietal white matter. Histological examination of the biopsied specimens showed demyelinated lesions, containing foamy macrophages and bizarre astrocytes. Oligodendrocytes contained nuclear inclusions which reacted with an antibody against the JC virus (JCV) antigen. These findings were consistent with those of PML. The genomic analysis of JCV from the biopsied brain revealed deletions in the regulatory region. We investigated cerebral blood flow, glucose and amino acid metabolism in this patient using positron emission tomography, and obtained the following three characteristic findings in the lesions: 1) luxury perfusion state, 2) decreased fluorodeoxyglucose (FDG) uptake, and 3) increased methionine (Met) uptake. These findings resembled those of low grade tumors.

Animals↗

Clinicopathological study of choroid plexus tumors: immunohistochemical features and evaluation of proliferative potential by PCNA and Ki-67 immunostaining.

This report concerns the retrospective immunohistochemical characterization and evaluation of the proliferative potential of eight choroid plexus tumors (CPTs) that included six cases of choroid plexus papilloma (CPP), one of whom had a recurrence, and two cases of choroid plexus carcinoma (CPC). Antibodies to prealbumin, glial fibrillary acidic protein (GFAP), vimentin, keratin, and carcinoembryonic antigen (CEA) were used to determine the immunohistochemical features of interest. The proliferative potential was evaluated with antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67. Antibody binding was visualized by the avidin-biotin-peroxidase complex (ABC) method. Immunoreactivity was scored on a-to 4+ scale, and in the case of PCNA and Ki-67, expected as staining index (SI). All seven CPP specimens were immunostained for prealbumin, but not for CEA. Expression of GFAP, vimentin and keratin varied from one CPP case to another. Both CPCs expressed CEA, but not prealbumin, GFAP and keratin; one of them was vimentin-positive. As determined by immunostaining for Ki-67, the proliferative potential was lower in the CPPs than in the CPCs. Among the former, the highest Ki-67 SI was seen in the primary lesion of a recurring papilloma. On the other hand, immunostaining for PCNA gave less consistent SI values. Our results show that immunohistochemical assays for prealbumin and CEA expression are of significant value for the differential diagnosis of CPPs and CPCs, and that high Ki-67 SI values may serve as an indicator of CPP recurrence, even if the primary lesion is benign.

Adult↗

[Sarcoidosis in a patient with autoimmune hemolytic anemia].

A 65-year-old woman was admitted to our hospital because of severe anemia. A skin biopsy was done in January 1994 and sarcoidosis was diagnosed. Diffuse reticular shadows were seen in both lung fields on a chest X-ray film and mediastinal lymph node swelling was seen on a chest CT scan. She was followed as an outpatient and was not treated. She suddenly experienced vertigo and general fatigue in March 1995. Laboratory findings on admission were as follows: Hb 6.2 g/dl, MCV 115.9 fl, Ret 198%, LDH 732 IU/L, I-Bil 1.9 mg/dl, and Coombs' test was positive. Autoimmune hemolytic anemia was diagnosed, and she was treated with prednisolone (1 mg/kg). As of the time of this writing, she has no relapse of hemolytic anemia though prednisolone was discontinued 6 months ago.

Anemia, Hemolytic, Autoimmune↗

[A patient with Sjögren syndrome with central pontine myelinolysis and hypokalemic myopathy].

We report a 42-year-old woman who presented with intermittent episodes of muscular weakness lasting approximate 7 to 10 days, about once a year, since 1985. During these episodes of weakness, hypokalemia and elevation of serum creatine kinase were noted. On admission, xerostomia, keratoconjunctivitis sicca (positive Schirmer test), abnormal sialographic findings (apple tree-like appearance), and positive serum autoantibodies against ss-A and nucleus were noted. These findings were compatible with Sjögren syndrome. She also had hyperchloremic metabolic acidosis with normal anion gap, hypokalemia and renal calcifications. Therefore, she had renal tubular acidosis (type 1) in addition to Sjögren syndrome. Brain magnetic resonance imaging (MRI) demonstrated a symmetrical circumscribed lesion in the ventral part of the central pons. We considered this lesion to be central pontine myelinolysis (CPM), because of its typical location and characteristic MRI appearance. This CPM was clinically silent. Pathogenesis and etiology of CPM are obscure, and CPM associated with hypokalemia without hyponatremia has rarely been reported in the literature. However, this is the first report of CPM associated with Sjögren syndrome and hypokalemic myopathy complicated with renal tubular acidosis.

Acidosis, Renal Tubular↗

Human immunodeficiency virus type 1 reverse transcriptase: enhancement of activity by interaction with cellular topoisomerase I.

A number of studies have suggested that topoisomerase I (topo I) activity may be important in human immunodeficiency virus type 1 (HIV-1) replication. Specifically it has been reported that purified virus particles have topo I activity and that inhibitors of this enzyme can inhibit virus replication in vitro. We have investigated a possible association of HIV-1 gag proteins with topo I activity. We found that whereas the gag-encoded proteins by themselves do not have activity, the nucleocapsid protein p15 can interact with and enhance the activity of cellular topo I. Furthermore it could be demonstrated that topo I markedly enhanced HIV-1 reverse transcriptase activity in vitro and that this could be inhibited by the topo I-specific inhibitor camptothecin. The findings suggest that cellular topo I plays an important role in the reverse transcription of HIV-1 RNA and that the recruitment of this enzyme may be an important step in virus replication.

Base Sequence↗

Establishment and characterization of a carrier cell culture producing high titres of polyoma JC virus.

This report concerns a carrier cell culture (designated JCI) infected persistently with JC virus (JCV). Immunostaining with an anti-JCV antiserum revealed that JCI was a carrier culture in which only a small fraction of the cells (approximately 1.5%) produced the virus. The JCV titre was increased strikingly by incubating confluent JCI cells for 4-6 days in medium containing a low concentration of fetal bovine serum (2%). Viral genomes cloned from the persistently infected JCI cells were heterogeneous with respect to size, but most clones had an alteration of the same regulatory region (designated CR-JCI). Transfection experiments with a chimeric JCV DNA (Mad-1/CR-JCI), in which the regulatory region was CR-JCI and the other region was derived from an infectious JCV (Mad-1) DNA, showed that CR-JCI was less efficient in inducing viral growth than the regulatory regions of IMR-32-adapted JCVs. The transfected cells could be readily subcultured, and they continued to produce JCV. It is concluded that a decrease in the activity of the JCV regulatory region is of importance for the maintenance of the carrier state of JCI cells.

Animals↗

Expression of renin and angiotensin-converting enzyme in human hearts.

To understand the significance of the tissue renin-angiotensin system in the heart, we examined the expression of renin and angiotensin-converting enzyme (ACE) in autopsied human hearts. Samples were taken from organs obtained at autopsy from 15 patients without heart disease and 3 patients with heart disease (old myocardial infarctions, acute myocardial infarctions, and hypertrophic cardiomyopathy). We examined the expression of renin and ACE mRNA by using the reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR showed the expression of renin in the right atria in all patients. However, expression of renin mRNA in the left ventricles was not found in any of the 15 hearts without heart disease. In contrast, renin mRNA was detected in the left ventricles in hearts with heart disease. ACE mRNA was detected in both the atria and the ventricles in normal hearts, and its expression did not alter in diseased hearts. These findings suggest that renin mRNA is expressed mainly in the right atria in normal hearts, but that its expression in the left ventricle can be activated in some pathological conditions.

Adult↗

Retrospective analysis of biological factors in a recurrent IV-S neuroblastoma with intermediate-grade malignancy.

A clinical stage of IV-S neuroblastoma is known to include heterogeneous tumors. The authors report a case of IV-S neuroblastoma that relapsed after regression 4 years and 10 months after diagnosis. Multiagent chemotherapy was necessary to control the disease, and the patient has been doing well with no evidence of disease for more than 5 years. Although Shimada's classification showed favorable characteristics, N-myc protein was positive and DNA ploidy was diploidy in the tumor at diagnosis. Discrepancy in DNA ploidy was observed and aneuploidy was shown in tumor specimens at recurrence. Experience in this case showed the following important clinical features: (1) IV-S neuroblastoma of intermediate-grade malignancy does exist, and patients with such a disease may be cured by aggressive treatment; (2) Identifying IV-S patients with an unfavorable clinical course is possible by examining biological prognostic factors.

Adrenal Gland Neoplasms↗

Prognostic significance of an interface pattern of central fibrosis and tumor cells in peripheral adenocarcinoma of the lung.

Fifty-nine surgically resected pulmonary adenocarcinomas were histologically classified into four types (A, B, C, and D) according to the pattern of invasion, ie, the extent of invasive tumor cell growth in the interface zone between alveoli replaced by cancer cells and the central region of fibrosis (so-called "scar"). In pattern A cancer cells proliferate along the alveolar walls without forming a frankly invasive lesion. In pattern B invasive lesions occupy less than 30% and in pattern C more than 30% of the fibrosing area. Pattern D refers to invasion of the bronchial lumen by cancer cells. The 59 tumors included 14 of pattern A, 12 of pattern B, 16 of pattern C, and 17 of pattern D. The 5-year survival rate for patients with pattern A tumors was 100%, and the rates for patients with pattern B, C, and D tumors were 64.2%, 30.0%, and 11.8%, respectively. Each difference between pairs of survival curves was statistically significant (P < .05). We found a correlation between the pattern of invasion and other prognostic factors. However, even in the cases evaluated as favorable by other prognostic factors (stage I, tumor less than 35 mm in diameter, negative for lymph node metastases, well-differentiated histology, negative for subpleural invasion, negative for vascular invasion) the survival curves became steeper going from pattern A to patterns B, C, and D. We conclude that the pattern of invasion is correlated with the prognosis of surgically treated patients. Our study may provide new histological criteria for the prognostic evaluation of pulmonary adenocarcinoma.

Adenocarcinoma↗

Nucleotide sequence and restriction fragment length polymorphism analysis of the long terminal repeat of human T cell leukemia virus type II.

Molecular studies have demonstrated the existence of two major subtypes of human T cell leukemia virus type II: HTLV-IIa and HTLV-IIb. In attempts to further classify this family of viruses we have carried out nucleotide sequence and restriction fragment length polymorphism (RFLP) analysis of the long terminal repeat (LTR), a region that has been shown in previous studies to have the greatest intra- and intersubtype genomic divergence. Analysis of the nucleotide sequences suggested the existence of distinct phylogenetic groups in each subtype and, on the basis of predicted differences in restriction endonuclease sites, RFLP analysis allowed the identification of four groups within the IIa subtype (a1-a4) and six within the IIb subtype (b1-b6). Nucleotide sequence analysis also suggested the possible existence of HTLV-II quasispecies. However, this appeared not to be significant, and preliminary studies suggest that these would not be expected to influence the results of RFLP analysis appreciably. The validity of the RFLP method was demonstrated in an analysis of 36 randomly chosen samples from HTLV-II seropositive blood donors from the New York City Blood Center, where it could be shown that all could be successfully classified. Moreover, the RFLP analysis correctly matched the viruses in donors and recipients of contaminated blood in four situations in which HTLV-II was inadvertently transmitted by transfusion. RFLP analysis of the LTR appears to be a rapid and reliable method by which to identify HTLV-II infection. This should prove useful in studies of the epidemiology and the characterization of viruses present both in nonindigenous and indigenous populations.

Base Sequence↗

A novel point mutation (R243Q) in exon 7 of the c-erbA beta thyroid hormone receptor gene in a family with resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) is characterized by variable tissue hyporesponsiveness to thyroid hormones. Recently, a large number of different point mutations have been identified in the c-erbA beta thyroid hormone receptor (TR beta) in subjects with RTH. We describe a Japanese family with RTH with a novel point mutation in exon 7 of the TR beta gene. A single nucleotide substitution, guanine for adenine, was identified at the second position of codon 243 located in the hinge domain between the ligand binding and DNA binding domains in one of the two alleles of the proband and his mother, resulting in the substitution of the normal arginine (CGG) with a glutamine (CAG). Except for one family, point mutations so far described in RTH are clustered at exons 8-10 of the TR beta gene. This report presents a novel mutation in the characteristic portion in exon 7 of the TR beta.

Amino Acid Sequence↗

Treatment of a stage I testicular yolk sac tumor with vascular invasion.

There is controversy concerning the treatment of stage I yolk sac tumor of the testis, particularly of those with histological factors that indicate a high risk of relapse. Usually orchiectomy alone is sufficient and adjuvant chemotherapy is unnecessary. Retroperitoneal lymphadenectomy is indicated for patients with persistently high alpha-fetoprotein. Once recurred, treatment at that time is thought to be curative. However, postoperative chemotherapy may be necessary for patients with a tumor expressing histological factors that predict possible relapse. In this paper we report on a case of a 2 year old boy whose tumor invaded the testicular veins. The patient suffered from recurrent disease but was successfully treated by chemotherapeutic regimens including cisplatin and retroperitoneal lymphadenectomy. The importance of the histological factors in making a decision on the treatment strategy for stage I testicular yolk sac tumor is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

A sex reversal infant with XX karyotype and complete male external genitalia.

The unusual case of a Japanese newborn XX male is presented. Examination of chromosomes in amniotic fluid cells had shown a normal female karyotype (46,XX), but ultrasonography revealed a penis and a scrotum. The neonate had normal male external genitalia, and serum levels of luteinizing hormone, follicle stimulating hormone, and testosterone were all within the normal range. High resonance chromosome analysis revealed an excess portion on the short arm of one of the X chromosomes. We examined his genomic DNA by polymerase chain reaction (PCR) and detected two Y specific regions in his genomic DNA, the sex-determining region Y (SRY) and pseudoautosomal boundary Y. Nucleotide sequencing of the PCR products of SRY indicated no mutation. These findings suggested that the translocation or insertion of an SRY region on the X chromosome led to the development of testicles and a male phenotype.

Base Sequence↗

Relationship between atrial natriuretic peptide and plasma volume during graded exercise with water immersion.

To assess the relationship between atrial natriuretic peptide (ANP) and the reduction in plasma volume (PV) during exercise, we measured changes in PV and ANP in seven male volunteers during treadmill exercise in air (AE) and with water immersion (WE) together with time control studies of rest in air and in water. Blood samples were collected from a catheter in the antecubital vein at exercise intensities of 32, 49, 65, and 78% of peak oxygen consumption (VO2). Plasma ANP in AE increased significantly from the resting value [15 +/- 1 (SE) pg/ml] only at 78% of peak VO2 (29 +/- 5 pg/ml), whereas ANP in WE increased significantly at exercise levels of > 49% of peak VO2 and reached 68 +/- 9 pg/ml at 78% of peak VO2. Although PV in AE and WE decreased significantly with VO2 of > 49% of peak VO2 (P < 0.01), the decrease from the resting value in WE was significantly greater than that in AE of > 65% of peak VO2 (P < 0.01) and the decreases at 78% of peak VO2 were -9.7 +/- 0.8 and -6.1 +/- 1.7%, respectively. The difference in the decrease in PV between AE and WE at corresponding VO2 correlated strongly with that in the increase in ANP (r = -0.97; P < 0.01). These results are consistent with the hypothesis that ANP may be involved in the fluid shift from the intra- to extravascular space during exercise.

Adult↗

Human pulmonary vascular and venous compliances are reduced before and during left-sided heart failure.

Human pulmonary vascular and venous compliances were measured in 41 patients with or without left-sided heart failure. Two methods were used. Method 1 was based on analysis of pulmonary capillary wedge (PCW) pressure tracings according to Cv,PCW = (SF/100)(0.075PCW + 0.90)SV/[(v - d)PCW + 1], where Cv,PCW is compliance of pulmonary venous system, SF is systolic fraction of pulmonary venous flow [related to pulmonary capillary wedge pressure (PCW) as SF = 82 - 2.01PCW], (v - d)PCW is pulse pressure in PCW position, and SV is stroke volume. The (0.075PCW + 0.90) term equals k", i.e., systolic run-off ratio. Method 2 was used to measure to pulmonary vascular volume-pressure (V-P) relationship and pulmonary vascular compliance (Cvasc) and is based on measurement of pulmonary blood volume (PBV) and its increase with passive elevation of the legs to calculate Cvasc. Assuming the proportion of blood entering pulmonary venous system (in increase of PBV) during passive leg elevation to be 0.8, pulmonary venous compliance (Cv,PBV) was calculated as Cv,PBV = 0.8Cvasc. Cv,PCW correlated fairly closely with Cv,PBV (r = 0.81, coefficient of variation = 31%). This fair agreement between two independent methods suggests strongly that both methods may be valid, although other interpretations are possible. Cv,PCW, Cvasc, and Cv,PBV decreased going from New York Heart Association class I to classes II and III. When PBV was plotted vs. PCW, average V-P line for class II patients was flatter and shifted downward to the right compared with that for class I. This suggests pulmonary vasoconstriction as well as other factors. Average V-P line for class III patients is flatter but not displaced compared with that for class II. Another previously reported series of 50 patients, most of whom had ischemic heart disease, are included in this study.

Blood Pressure↗

Gamma Knife surgery for angiographically occult vascular malformations.

To evaluate the effect of radiosurgery on angiographically occult vascular malformations (AOVMs), 9 patients treated with Gamma Knife surgery were followed up for 21-37 months. Eight patients had bleeding episodes, 1 had uncontrollable epilepsy. Rebleeding occurred in 3 AOVMs 5 or 6 months after treatment. One patient experienced transient radiation-induced edema. One patient underwent surgical extirpation due to uncontrollable epilepsy 21 months after Gamma Knife surgery. Histological findings revealed an arteriovenous malformation (AVM) and a cavernous angioma. There was hypertrophy of the internal membrane of the AVM, but no effect on the cavernous malformation. Radiosurgery should only be considered in cases of inoperable AOVM, because there is no definite proof that radiosurgery prevents AOVMs from rebleeding.

Adolescent↗

An autopsy case of incomplete left atrial rupture following left atrial infarction associated with left ventricular myocardial infarction.

We report a 78-year-old woman with incomplete left atrial rupture following left atrial infarction associated with left ventricular myocardial infarction. An autopsy revealed a hemopericardium. A large hematoma was observed in the posterior wall of the left atrium and a few small tears were found on the same wall. Near its origin, the left circumflex artery was severely sclerotic and completely occluded by fresh thrombus. Histologic examination revealed that large intramural hematoma longitudinally dissected the inner third of the posterior wall of the left atrium, and transversely dissected through the necrotic tissue to the pericardial sac to result in rupture. Coagulation necrosis and intramyocardial hemorrhage were also observed throughout the entire left atrium and the postseptolateral wall of the left ventricle.

Aged↗