Sequence of a cDNA encoding human LRP (leukocyte common antigen-related peptide).
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Biomedical subjects
Publications and source records attributed to M Nishi.
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2-Hydroxy-5,5-dimethyl-1-pyrrolidinyloxy (DMPO-OH), which is known to be produced by spin trapping of hydroxyl radicals (.OH) with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and has been a good monitor for detecting .OH in biological systems, has been examined by EPR for its production scheme in the presence of iron ion. In an aqueous DMPO solution containing ferric ion (Fe3+), DMPO-OH was produced and addition of methanol, a good scavenger for .OH, to this solution led to an aminoxyl radical, DMPO-OCH3, instead of DMPO-CH2OH which is produced by DMPO spin trapping of .CH2OH arising from H-abstraction by .OH. Also EPR measurements at 77K indicated the formation of a chelate between DMPO and Fe3+. Based on these, it has been elucidated that DMPO-OH as well as DMPO-OCH3 is formed by the nucleophilic attack of water and methanol to the chelating DMPO, respectively.
Protein tyrosine phosphatases (PTPases) are a family of enzymes that specifically dephosphorylate phosphotyrosyl residues in selected protein substrates. To more fully understand the regulatory role of protein tyrosine phosphorylation and dephosphorylation in cellular signal transduction, characterization of PTPases is essential. Using the polymerase chain reaction and degenerate oligonucleotide primers corresponding to conserved amino acid sequences within the catalytic domain of PTPases, we have identified 11 PTPase-related human liver cDNA sequences. Five of these have not been described previously. These results indicate that, like protein tyrosine kinases, PTPases may also comprise a gene family with a large number of members.
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Endotoxin-induced uveitis (EIU) can be produced by systemic injection of endotoxin (ET). It is not clear yet why exclusive ocular involvement occurs in this model. To clarify this question and to establish the sequence of inflammatory events, EIU was induced in Lewis rats by footpad injection of Salmonella ET. Ocular inflammatory response (anterior chamber cells and proteins), aqueous inflammation mediators (thromboxane B2, prostaglandin E2, leukotriene B4 and substance P) and MHC class 2 (Ia) antigen expression in the ciliary body were monitored for 72 hours. Thromboxane B2 was detected early in the aqueous humor, peaking already 1 hour after ET injection. Prostaglandin E2 & leukotriene B4 peaks and a second peak of thromboxane B2 were recorded 18 hours after ET-injection, at the time of maximal ocular inflammation. MHC-class 2 expression was first detected in the ciliary body stroma at the vascular level 6 hours after ET injection and was massively expressed in the ciliary body epithelium at 18 and 72 hours. It is hypothesized that ciliary body endothelium is particularly sensitive to the effect of ET and is the site of thrombocyte adherence. Vascular damage leads in succession to cellular infiltration, release of inflammation mediators and disruption of blood-ocular barrier. MHC-class 2 expression is a secondary phenomenon and is probably at the origin of additional tissue damage from immune effector mechanisms.
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Islet amyloid polypeptide is the major protein component of the islet amyloid of patients with Type 2 (non-insulin-dependent) diabetes mellitus. Since the synthesis of a structurally abnormal or mutant protein may contribute to the formation of amyloid deposits, we have examined the possibility that a mutant form of islet amyloid polypeptide or its precursor contributes to the formation of islet amyloid in Type 2 diabetic patients. We have sequenced the islet amyloid polypeptide precursor coding regions of the gene of 25 patients with Type 2 diabetes. Genomic DNA fragments corresponding to exon 2 and 3 of the islet amyloid polypeptide gene were amplified from patients' peripheral blood leucocyte DNAs using the polymerase chain reaction and specific oligonucleotide primer sets, and then directly sequenced. The nucleotide sequences of the amplified regions of both alleles of the islet amyloid polypeptide gene of these 25 patients were identical to one another and to the sequence of an islet amyloid polypeptide allele isolated from a human fetal liver genomic library. These findings suggest that a primary structural abnormality of islet amyloid polypeptide or its precursor is unlikely to play a significant role in the formation of islet amyloid in Type 2 diabetic patients.
Fluctuations in the amount of vanillylmandelic acid (VMA) and homovanillic acid (HVA) were studied in random urine samples from 13 infants with neuroblastoma. In patients with a small tumour, many samples contained amounts below the cut off values, suggesting that detection of a patient with neuroblastoma depended on mathematical probability. Using high performance liquid chromatography a patient with a tumour of about 10 g may well be overlooked, whereas a patient whose tumour weighs over 30 g would probably be detected. With qualitative screening, although more likely to miss a patient with low VMA excretion, a patient with a tumour weighing over 50 g would be detected. In a thorough hospital examination care should be exercised in interpreting borderline values of VMA and HVA; excretion information suggesting the existence of a tumour may aid localization by radiological imaging procedures.
The present study examined the effects of subtotal oesophagectomy through a right thoracal and abdominal approach, on the postoperative water-electrolyte metabolism and cardio-pulmonary function of patients with thoracic oesophageal carcinoma. The primary water balance, total sodium intake, urinary NAG index, free-water clearance (CH2O), oxygen diffusion function of the lungs to aerate blood (DLO2-Index), and alpha-human atrial natriuretic polypeptide (alpha-hANP) were measured perioperatively until the seventh day. Subjects were divided by age according to whether they were older or younger than 70 years into 2 groups. In both groups, no change was observed in the primary water balance, total sodium intake, urinary NAG index or CH2O. However, all of the patients in the older group exhibited significantly higher alpha-hANP values than those in the control group, and the DLO2-Index was also higher in the former subjects during the first 3 days following surgery. It may be concluded that alpha-hANP is a hormone of considerable importance as it is secreted in large amounts in response to increased stress on the cardio-pulmonary system and serves to normalize the water balance causing this extra load.
The incidence of neuroblastoma in Sapporo City for the period before the enforcement of the mass screening of neuroblastoma (1974 to 1980) was compared with the period after it (1981 to 1987). No large difference was found in incidence between them. In 1981 to 1987 the occurrence cluster at 2 to 4 years of age found in the prescreening period disappeared and an accumulation of patients at 0 year of age was noted. The sensitivity of the mass screening was almost stable (76.9% to 80.0%) throughout the 7 years. By the mass screening system of Sapporo City, early detection will be expected in 60% to 70% of all the neuroblastoma patients, the deficiency of which is due to the patients who neglected the mass screening.
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To determine the biological significance of the 585-base-pair deletion in the env gene of Friend spleen focus-forming virus (SFFV) encoding a leukemogenic glycoprotein (gp55), we examined the pathogenicity of a constructed mutant SFFV (SFFVDF). In the SFFVDF genome, the env deletion was filled in with the corresponding env sequence of Friend mink cell focus-forming virus, whereas the 6-base-pair duplication and the single base insertion near the 3' terminus of SFFV env remained intact. SFFVDF was nonpathogenic in adult mice. During passage of SFFVDF through newborn mice, we recovered various pathogenic variant SFFVs. Molecular analyses of variant SFFV genome DNAs revealed the presence of a distinct deletion in each env gene, which was similar but not identical to that in the wild-type SFFV env. Starting with the SFFVDF genome DNA, other mutant SFFV genome DNAs were constructed in which the sequence coding for the gp70/p15E proteolytic cleavage site present in the SFFVDF genome was modified by oligonucleotide-directed site-specific mutagenesis to prevent the cleavage. These mutant SFFVs were also nonpathogenic. These results indicate that for the pathogenic activity of gp55, a certain env deletion is necessary which causes production of a gp70-p15E fusion protein with an absence of at least the N-terminal one-third of the p15E-coding region.
The coverage rates of six vaccines (BCG, polio, DPT, measles, mumps and varicella) and the prevalence of these diseases in Japan were investigated. It was found that 82.2% of children had been inoculated with BCG before their first birthday, and 85.4% were given two doses of polio vaccine before their second birthday. The high acceptance rates of these vaccines seem to be attributable to mass inoculations at health centers. On the other hand, the median age when the first dose of DPT vaccine was given was as late as 22 months. Mass administration of this vaccine during infancy should be performed since about one-quarter of the patients with diphtheria, pertussis or tetanus were less than one year old. The cumulative percentage for measles inoculation failed to reach 60% by the second birthday. Considering that the incidence of measles has not yet been satisfactory lowered and that infants under 23 months of age account for about one-half of this incidence, more children less than 18 months old should be immunized. The ineffective rate of varicella vaccine was found to be 18.2%, although reestimation of its effectiveness may be necessary.
The degu, Octodon degus, is a South American hystricomorph rodent that is of interest because it develops spontaneous diabetes mellitus and has been found to have islet amyloidosis. To help clarify these problems we have cloned cDNAs encoding islet amyloid polypeptide (IAPP), insulin, and glucagon precursors from this species. The predicted amino acid sequence of degu IAPP is very similar to that of nonamyloid-forming guinea pig IAPP. In contrast, degu insulin and the C-terminal region of degu glucagon are highly divergent from those of other mammals, as is also the case in the guinea pig, suggesting the existence of some form of positive evolutionary pressure on these hormones of carbohydrate metabolism in the hystricomorph rodents.
A known and a new caffeic ester (1 and 2), new inhibitors of xanthine oxidase (XO), were isolated from leaves of Perilla frutescens var. acuta and their structures have been established as (Z,E)-2-(3,4-dihydroxyphenyl)ethenyl ester (1) and (Z,E)-2-(3,5-dihydroxyphenyl)ethenyl ester (2) of 3-(3,4-dihydroxyphenyl)-2-propenoic acid, respectively, based on detailed spectral studies, including 2D COSY, long range COSY, difference NOE, etc. Both caffeic esters strongly inhibited XO in vitro and especially, the inhibition by 1 was as potent as that by allopurinol. The inhibition mode of 1 was also shown to be non-competitive.
Aminoxyl radical formation from DMPO in the presence of Fe ion was studied to clarify the ambiguous ESR signals obtained by spin trapping with DMPO. It was found that when DMPO was used in a Fenton system, a Fe-DMPO complex was formed immediately. This complex was subsequently attacked by oxidative species originating from H2O2 and thus oxidative degradation of DMPO was induced in the Fenton system. On the other hand, in the case of M4PO, the degradation was found to be very slow, indicating that the 3 position of DMPO was favorably attacked by the oxidative species. Some of the degradation products are probably aminoxyl radicals. This series of the degradation products are probably aminoxyl radicals. This series of reactions may compete with spin trapping and make it difficult to analyze ESR spectra obtained in the presence of Fe ion.
The metabolic response to the postoperative delivery of a sole glucose solution or a glucose-fructose-xylitol solution, and their effects upon carbohydrate metabolism, in patients with glucose tolerance impairment, were evaluated. Twenty four patients who showed an abnormal 75g-OGTT or were noninsulin-dependent diabetics were divided in two groups. The GFX-B group (n = 11) received a 10.5% solution, containing glucose, fructose and xylitol at 4:2:1 ratio, and the PHY-3 group (n = 13) received a 10% glucose solution, both, continuously infused for 3 days postoperatively. The infusion of PHY-3 tended to produce a higher increase in blood glucose than the infusion of GFX-B, that was significantly different on the 3POD (P less than 0.05). The increase in IRI and CPR was also significantly greater in PHY-3 group than in GFX-B group on the 3POD (P less than 0.05). We concluded that it was not only the slight lower glucose load of the GFX-B solution, but also, the different infused carbohydrate substrate which had influenced the magnitude of insulin secretion and the blood glucose level. Then, its use in glucose intolerant patients may be of some benefit to partially minimize the postoperative hyperglycemic response.