Biomedical subjects

M Shoji

Publications and source records attributed to M Shoji.

404 records · Page 23Linked to original sources

PubMedDate not supplied

The effect of edelfosine on CTP:cholinephosphate cytidylyltransferase activity in leukemic cell lines.

Analogs of ether phospholipids have been shown to have selective anti-neoplastic activity. The compounds are known to inhibit phospholipid biosynthesis. This paper examines the effect of the alkyl-lysophospholipid, edelfosine, on the rate-limiting enzyme, CTP:cholinephosphate cytidylyltransferase, in de novo phosphatidylcholine synthesis in sensitive and resistant leukemic cell lines. Enzyme activity was measured by the incorporation of 14C-phosphocholine into CDP-choline by lysates of HL60 and K562; cells demonstrated inhibition of incorporation of 14C-phosphocholine in HL60 cell lysates but no inhibition in K562 lysates. Partial purification of cytidylyltransferase by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting demonstrated similarity between the enzyme isolated from each cell line. Cloning and sequencing of cytidylyltransferase cDNA of HL60 cells was accomplished using a probe encoding the entire protein sequence of the K562 cytidylyltransferase gene. A substitution at nucleotide 751 from A in the HL60 cell cDNA clone to G in the K562 cDNA clone resulted in a change in amino acid number 251 from lysine (positively charged) in the HL60 enzyme to glutamic acid (negatively charged) in the K562 enzyme. This negative charge in the lipid-binding domain of the K562 enzyme may result in a weaker binding of edelfosine and the observed decrease in activity, as evidenced by resistance to edelfosine by K562 cells.

Antineoplastic Agents↗

PubMedDate not supplied

The levels of cerebrospinal fluid Abeta40 and Abeta42(43) are regulated age-dependently.

Decreased levels of cerebrospinal fluid (CSF) Abeta42 is a diagnostic marker of Alzheimer's disease. To clarify the biological basis of this marker, the physiological alterations of CSF Abeta40 and Abeta42 by aging were studied. CSF samples from 92 normal subjects between 8 and 89 years old were measured using a specific ELISA for Abeta40 and Abeta42(43). High concentrations of Abeta40 and Abeta42(43) in the young group, under 29 years old, changed to be at low concentrations in the adult group between 30 and 59 years old. Subsequently, the levels increased again with age. Third order regression analysis showed a significant correlation between the levels of Abeta40 and age (Y = - 169 X(3) + 3.1X(2)- 0.02X + 4135; P < 0.034) and between the levels of Abeta42(43) and age (Y = - 46 X(3) + 0.9 X(2)- 0.005X + 992; P < 0.005). The levels of CSF Abeta40 and Abeta42(43) were physiologically regulated to show a U-shaped natural course in normal aging. These findings suggested that the physiological increase of Abeta42(43) over 59 years of age is selectively inhibited in Alzheimer's disease.

Adolescent↗

PubMedDate not supplied

Accumulation of amyloid beta protein in transgenic mice.

Carboxyl-terminal fragments of beta amyloid precursor protein (betaAPP) were expressed in mice under the transcriptional control of an ubiquitous promoter system, based upon a chicken beta-actin (betaA) promoter combined with cytomegalovirus (CMV) enhancer to obtain a systemic overproduction of amyloid beta protein (Abeta). Three transgene constructs were designed to encode signal peptide and carboxyl-terminal 99 amino acid residues to betaAPP (NOR-beta), methionine and C-terminal 103 amino acid residues of betaAPP (deltaNOR-beta), and methionine and C-terminal 103 amino acid residues with KM-NL substitution of betaAPP (deltaNL-beta). Although the transcriptional mRNA level and post-translational protein level from transgenes showed the same expression pattern, both the expression of Abeta and distribution of Abeta deposits were completely different among these strains. In NOR-beta mice, considerable amounts of Abeta were detected in plasma and Abeta deposits were observed in the pancreas. Brain Abeta deposits and small amounts of plasma Abeta were recognized in deltaNL-beta. These findings indicate that tissue specific processing and transgene constructs are major factors to determine the distribution of Abeta deposits.

Actins↗

PubMedDate not supplied

Alcohol-related sudden death with hepatic fatty metamorphosis: a comprehensive clinicopathological inquiry into its pathogenesis.

To clarify the pathogenesis of the widely known but obscure syndrome of sudden death with hepatic fatty metamorphosis observed in alcohol abusers, we have scrutinized both the clinical and pathological data of 11 subjects who died under such circumstances between 1987 and 1993. Death followed several days of uninterrupted drinking often with little dietary intake. The notable clinical features on arrival at the emergency room were disturbance of consciousness (11/11), hypotension (4/6), hypothermia (3/5), hypoglycaemia (8/11), metabolic acidosis (6/6), renal dysfunction (11/11), and hyperammonaemia (5/5). The common hepatic pathology was the extensive appearance of numerous microvesicular fatty droplets in the hepatocytes together with varying degrees of macrovesicular fatty change; four subjects had an underlying cirrhosis. Death undoubtedly results from a variety of metabolic disturbances triggered by the combination of massive ethanol intake and starvation. The appearance of extensive microvesicular fatty change superimposed on macrovesicular fatty change was considered to be an associated phenomenon.

Adult↗

PubMedDate not supplied

Expression of thymidine phosphorylase as an effect prediction factor for uterine cervical squamous cell carcinoma after radiotherapy: an immunohistochemical study.

Prognoses in cases of uterine cervical squamous cell carcinoma treated with radiotherapy were investigated in association with immunohistochemical expression of an angiogenic factor, thymidine phosphorylase (TP). Forty-six cases of uterine cervical squamous cell carcinoma mainly treated with radiotherapy during 1992-2001 at our clinic were studied. All were diagnosed as stages IIB to IVA. Paraffin-embedded biopsy specimens excised before radiotherapy were stained immunohistochemically using anti-TP monoclonal antibody. The extent of staining in both tumor and interstitial cells was graded as (-), (+/-), (+), and (2+). Specimens with TP expression levels of (2+) and (+) were regarded as positively stained and those with TP expression levels of (+/-) and (-) as negatively stained. The efficacy of radiotherapy in both groups was analyzed by the Kaplan-Meier method. With tumor cells, 5-year survival rates for the positive (n= 38) and negative (n= 8) staining groups were 73.9% and 42.9%, respectively; the rate being significantly higher for the TP-positive group (log rank, P= 0.0096). Contrarily, with staining for interstitial cells, the 5-year survival rates for the positive (n= 20) and negative (n= 26) staining groups were 74.1% and 64.6%, respectively, with no significant difference (log rank, P= 0.406). The efficacy of radiotherapy in the group with positive staining of tumor cells was significantly better than in the negative staining group. Immunohistochemical expression of TP in tumor cells is suggested as a useful prognostic factor for uterine cervical squamous cell carcinomas treated with radiotherapy. Choosing therapy for individual cases by referring to factors including TP expression should contribute to an improved prognosis.

Aged↗

PubMedDate not supplied

Neurodegeneration and gliosis in transgenic mice overexpressing a carboxy-terminal fragment of Alzheimer amyloid-beta protein precursor.

In order to study the properties of beta-amyloid in vivo, we generated a total of 28 transgenic founder mice that harbored the gene for the 17-amino acid signal sequence and the 99-amino acid carboxy-terminal fragment (CTF) of the human amyloid-beta protein precursor (beta APP) linked to the cytomegalovirus enhancer and chicken beta-actin promoter. Two of these founders, termed 0304 and 0809, exhibited decreased behavioral activity with gliosis and neurodegeneration in the hippocampus at 2.5 and 9 months of age. Both mice had also decreased levels of synaptophysin, a presynaptic marker, but no evidence for beta-amyloid deposition in their brains. Neurodegeneration in the hippocampus was transmitted to the offspring of mouse 0304, although the frequency was low (5 of 44 mice examined) and the time of onset of the disorder was rather later than that in the founder mouse. This is probably due to reduced levels of the transgene-derived products in the offspring of mouse 0304. The 0809 line failed to produce its offspring. The other remaining transgenic founders appeared normal and had lesser amounts of the CTF mRNA and protein in their brains than did 0304 and 0809 founders, though some mice died in earlier stages or exhibited hydrocephalus. These findings suggest that overexpression of the CTF of human beta APP has the potential to elicit neurodegeneration in vivo without appreciable production of beta-amyloid fibrils.

Amyloid beta-Protein Precursor↗

PubMedDate not supplied

Hand-Schüller-Christian disease with occult diabetes insipidus, cardiac failure and renal dysfunction.

A 60-year-old man was diagnosed as Hand-Schüller-Christian disease due to the triad of exophthalmus, decalcification of the bone, and diabetes insipidus. He had xanthogranuloma on the face and a nuchal region, and unusual complications of ADH-resistant diabetes insipidus due to renal dysfunction, and chronic cardiac failure. Urine osmolality was hypotonic, but urine volume was within the normal limit, despite the presence of central diabetes insipidus. Hypophyseal, adrenal and thyroid function were not remarkable. The skin biopsy showed the infiltration of eosinophilic granuloma cells. Treatment with vincristine was effective to regress the xanthogranuloma. Diabetes insipidus was not treated because of the absence of polyuria and polydipsia.

Acute Kidney Injury↗

PubMedDate not supplied

Metabolism of N-nitrosomethylbenzylamine in the mongolian gerbil (meriones unguiculatus).

Adult male gerbils (Meriones unguiculatus) received a single s.c. injection of N-nitroso(methyl-14C) methylbenzylamine (2.5 mg/kg body weight). Of the radioactivity injected 46% was exhaled as 14CO2 within 8-10 hours and an additional 21% was excreted as urinary metabolites. Six hours after injection of the carcinogen, methylation of DNA bases was highest in lung (81.5 mumol 7-methylguanine/mol guanine) followed by liver, esophagus, kidney, forestomach, glandular stomach, spleen, colon and small intestine. The brain DNA no alkylation products were detectable. These data differ significantly from those obtained in rats and mice which under similar experimental conditions metabolized N-nitrosomethylbenzylamine preferentially in esophagus and liver respectively.

Animals↗