Biomedical subjects

E Nishiyama

Publications and source records attributed to E Nishiyama.

18 recordsLinked to original sources

PubMed1999

Assessment of cerebrospinal fluid levels of serum amyloid P component in patients with Alzheimer's disease.

Serum amyloid P component (SAP) is a normal plasma constituent that is observed both in senile plaque and in neurofibrillary tangle in brains of patients with Alzheimer's disease (AD). In this study, we evaluated the SAP levels in cerebrospinal fluid (CSF) of 72 patients with AD, 11 frontotemporal dementia and nine normal control subjects. There was no significant difference in the SAP levels between the AD group and other groups. However, among AD patients, cognitive function was rated using the Mini-Mental State Examination and was correlated with the SAP level (R = 0.38, P < 0.05). Our results suggest that measurement of the SAP levels in CSF can be useful for assessing the degree of cognitive impairment in AD patients.

Aged↗

PubMed1999

Function of poly(ADP-ribose) polymerase in response to DNA damage: gene-disruption study in mice.

To elucidate the biological functions of poly(ADP-ribose) polymerase (PARP, [EC 2.4.2.30]) in DNA damage responses, genetic and biochemical approaches were undertaken. By disrupting exon 1 of the mouse PARP gene by a homologous recombination, PARP-deficient mouse embryonic stem (ES) cell lines and mice could be produced without demonstrating lethality. PARP-/- ES cells showed complete loss of PARP activity and increased sensitivity to gamma-irradiation and an alkylating agents, indicating a physiological role for PARP in the response to DNA damage. p53, a key molecule in cellular DNA damage response, was found to stimulate PARP activity and became poly(ADP-ribosyl)ated in the presence of damaged DNA. However, PARP-/- ES cells showed p21 and Mdm-2 mRNA induction following gamma-irradiation, indicating that PARP activity is not indispensable for p21 and Mdm-2 mRNA induction in the established p53-cascade. On the other hand, in a reconstituted reaction system, purified PARP from human placenta suppressed the pRB-phosphorylation activity in the presence of NAD and damaged DNA. Human PARP expressed in E. coli showed a similar effect on pRB-phosphorylation activity of cdk2. These findings suggest a direct involvement of PARP in the regulation of cdk activity for cell-cycle arrest.

Animals↗

PubMed1997

Distribution of apolipoprotein E in senile plaques in brains with Alzheimer's disease: investigation with the confocal laser scan microscope.

In order to elucidate the mechanism of the occurrence of apolipoprotein E (ApoE) in senile plaques (SP) in the brain of Alzheimer's disease (AD) patients, we morphologically examined double immunofluorescent-stained sections by scanning with the confocal laser scan microscope (LSM) and reconstructed their three-dimensional structure by a computerized imaging technique. Brain samples were obtained from six pathologically diagnosed AD patients, including patients with the genotype ApoE epsilon 3/3 and epsilon 4/4 ApoE genotype. We found some clear differences in distribution and shape in the staining patterns of plaque-shaped deposits by ApoE antibody and amyloid beta-protein (A beta) antibody. ApoE deposits were generally larger than A beta deposits in the same region and were distributed widely at the periphery of A beta deposits. Several A beta deposits of typical, compact and primitive plaques were often included in one diffuse plaque-like deposit of ApoE. Some ApoE deposits did not exhibit any A beta-immunoreactivity. Each core represented by ApoE and A beta did not show complete overlap. Typical plaques tended to be composed mainly of A beta-immunoreactivity and had little ApoE-immunoreactivity. The discrepancy between ApoE and A beta deposition may reflect different stages of amyloidogenesis in SP. The presence of ApoE alone in plaques may represent the pathological stage before the beginning of massive A beta deposition.

Aged↗

PubMed1997

Distribution of amyloid deposits in the cerebral white matter of the Alzheimer's disease brain: relationship to blood vessels.

The relationship between blood vessels and amyloid beta (A beta)-protein deposits in the cortex of the Alzheimer's disease (AD) brain is still controversial. It is difficult to distinguish whether the A beta deposits are associated with blood vessels or neurons because of their widespread and complicated distribution. In this study, we investigated the distribution of A beta deposits in the cerebral white matter of the AD brain as a means of removing the bias of neuronal distribution. An immunohistochemical study of 100 serial sections, after pretreatment with formic acid for 24 h, revealed the presence of A beta deposits in the cerebral white matter of the AD brain. There are various morphological types of plaques containing A beta deposits in the white matter, the same as in the gray matter. While the majority of A beta deposits was of a circumscribed type such as "classic" and "primitive" plaques, "compact" and "diffuse" plaques were also observed in the white matter. The location of the A beta deposits was, for the most part, immediately beneath the gray matter. The distribution of A beta deposits in the white matter was found to correspond to the orientation of the blood vessels. Serial sections also revealed that these A beta deposits were distributed along a single blood vessel. These findings suggest that the deposition of A beta in the cerebral white matter is primarily related to the blood vessels.

Aged↗

PubMed1997

Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis.

Liver fibrosis/cirrhosis is characterized by hyper-accumulation of fibrous tissue components and is commonly observed in later or terminal states of chronic hepatic diseases. In ongoing work, we found that the administration of human recombinant hepatocyte growth factor (hrHGF) suppressed the onset of liver fibrosis/cirrhosis in several distinct models and accelerated the recovery from liver fibrosis/cirrhosis in rats. Repeated administration of porcine serum for 10 weeks to rats induced liver fibrosis without any accompanying hepatocellular injuries; in addition, the intravenous (i.v.) administration of hepatocyte growth factor (HGF) to these rats suppressed increases in fibrous components and hydroxyproline contents in the liver, thus preventing the onset of liver fibrosis. Repeated administration of dimethylnitrosamine (DMN) for four weeks induced liver cirrhosis, as characterized by the hyper-accumulation of fibrous components, infiltration of mononuclear leukocytes, and hepatic dysfunction. When HGF was injected daily for four weeks along with DMN-treatment, the onset of DMN-induced hepatic fibrosis/cirrhosis was suppressed; the numbers of infiltrating mononuclear cells, fibrous tissue components, and hydroxyproline content in the liver were decreased. When HGF was injected for two weeks following four weeks of DMN-treatment, HGF accelerated the recovery from liver cirrhosis and prevented death due to hepatic dysfunction. Likewise, HGF-injection suppressed the onset of liver fibrosis, when liver fibrosis had been induced by long-term treatment with carbon tetrachloride (CCl4). Thus, the administration of HGF holds great promise for treating subjects with liver fibrosis/cirrhosis as a result of chronic hepatic injury.

Alanine Transaminase↗

PubMed1994

Characterization of high-molecular-mass heat shock proteins and 42 degrees C-specific heat shock proteins of murine cells.

There are two isoforms of high-molecular-mass heat shock protein (HMM-HSP), hsp105A and hsp105B, in murine FM3A cells. To characterize the HMM-HSPs, we here purified hsp105A and hsp105B, as well as 42 degrees C-specific HSPs that are specifically induced by continuous heating at 42 degrees C, from the cytoplasmic extracts of the FM3A cells heat-shocked at 42 degrees C for 8 h. Digestion of the hsp105A, hsp105B, and 42 degrees C-specific HSPs with lysyl endopeptidase generated 17,000-Da polypeptide fragments in common, and the N-terminal amino acid sequences of the fragments revealed a homology with those of the adenosine binding domain of hsp70 family proteins and actin. Thus, the two isoforms of hsp105 and the 42 degrees C-specific HSPs seemed to be very similar proteins having a ATP binding domain in common, and these HSPs may constitute a HMM-HSP family in murine cells.

Amino Acid Sequence↗

PubMed1994

Demonstration of CRP immunoreactivity in brains of Alzheimer's disease: immunohistochemical study using formic acid pretreatment of tissue sections.

C-reactive protein (CRP) is a well-known serum protein which increases during inflammation and deposits in damaged tissues. To establish whether CRP appears in brain of Alzheimer's disease (AD), we immunohistochemically investigated tissue sections which were pretreated with formic acid. Positive immunostaining by anti-CRP antibodies was clearly recognized in senile plaques (SP) in the pretreated tissue sections, with very weak immunostaining in non-treated sections. These findings may suggest that the formation process of SP includes an acute-phase inflammatory state.

Aged↗

PubMed1994

Cellular localization of high-molecular-mass heat shock proteins in murine cells.

We have previously prepared an antiserum raised against hsp105 of murine FM3A cells. The anti-hsp105 serum reacted to two isoforms of high-molecular-mass heat shock protein (HMM-HSP) having a molecular mass of 105,000 Da (hsp105A and hsp105B) in FM3A cells. While hsp105A and hsp105B were both synthesized and accumulated under non-stressed conditions, upon exposure to heat shock much more hsp105B was induced than hsp105A. When the cellular distribution of these hsp105s in murine 3T3 Swiss albino and C3H 10T1/2 cells was examined by immunofluorescence methods using the anti-hsp105 serum, the HMM-HSPs were localized in the cytoplasm and nuclei and were never found in the nucleoli of both 3T3 and C3H cells under non-stressed and stressed conditions.

3T3 Cells↗

PubMed1993

Selective loss of calbindin D28K-immunoreactive neurons in the cortical layer II in brains of Alzheimer's disease: a morphometric study.

To investigate the relationship between neuronal death and intracellular calcium homeostasis in brains from patients with Alzheimer's disease (AD), we quantitatively analyzed morphological changes of calbindin-immunoreactive neurons. Neuronal counts were made in the autopsy brains from 6 control and 6 AD patients. Calbindin-immunoreactive neurons were mainly distributed in cortical layer II and were selectively lost in the AD brains. Further, the number of calbindin-immunoreactive neurons showed a negative correlation with age in the control group. These findings strongly suggest that age-related reduction of calbindin-immunoreactive neurons may be exaggerated in AD brains and change in calcium homeostasis may be involved in the pathogenesis of AD.

Age Factors↗

PubMed1989