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2.  Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers 
Neurology  2012;78(1):55-61.
The goal of the current investigation was to examine a cohort of symptomatic and asymptomatic LRRK2 mutation carriers, in order to address whether the reported alterations in amyloid β (Aβ) and tau species in the CSF of patients with sporadic Parkinson disease (PD) are a part of PD pathogenesis, the aging process, or a comorbid disease in patients with PD, and to explore the possibility of Aβ and tau as markers of early or presymptomatic PD.
CSF Aβ42, total tau, and phosphorylated tau were measured with Luminex assays in 26 LRRK2 mutation carriers, who were either asymptomatic (n = 18) or had a phenotype resembling sporadic PD (n = 8). All patients also underwent PET scans with 18F-6-fluoro-l-dopa (FD), 11C-(±)-α-dihydrotetrabenazine (DTBZ), and 11C-d-threo-methylphenidate (MP) to measure dopaminergic function in the striatum. The levels of CSF markers were then compared to each PET measurement.
Reduced CSF Aβ42 and tau levels correlated with lower striatal dopaminergic function as determined by all 3 PET tracers, with a significant association between Aβ42 and FD uptake. When cases were restricted to carriers of the G2019S mutation, the most common LRRK2 variant in our cohort, significant correlations were also observed for tau.
The disposition of Aβ and tau is likely important in both LRRK2-related and sporadic PD, even during early phases of the disease. A better understanding of their production, aggregation, and degradation, including changes in their CSF levels, may provide insights into the pathogenesis of PD and the potential utility of these proteins as biomarkers.
PMCID: PMC3466497  PMID: 22170881
3.  Authors' reply 
Gut  2007;56(10):1479-1480.
PMCID: PMC2000284
mantle cell lymphoma; combination chemotherapy
4.  A case of exacerbation of ulcerative colitis induced by combination therapy with PEG‐interferon α‐2b and ribavirin 
Gut  2006;55(11):1682-1683.
PMCID: PMC1860123  PMID: 17047132
adverse reactions; chronic hepatitis C; PEG interferon; ribavirin; ulcerative colitis
5.  Deep lamellar keratoplasty by deep parenchyma detachment from the corneal limbs 
The British Journal of Ophthalmology  2005;89(12):1597-1600.
Aim: To improve the deep lamellar keratoplasty technique.
Method: For the easy and reliable perfomance of deep lamellar keratoplasty (DLKP), detachment of Descemet’s membrane through the corneal limber flap was improved. To expose Descemet’s membrane, the parenchyma was detached by hydrodelamination through a sclerocorneal flap made in the corneal limbs. The parenchyma was removed after the pseudochamber between it and Descemet’s membrane was maintained with viscoelastic material. The corneal graft was placed with a running suture. 22 eyes were treated.
Results: Complete exposure of Descemet’s membrane was obtained in 20 of the 22 eyes (91%). The membrane was perforated in five of the 22 eyes (23%) during surgery, and two of the 22 eyes (9%) were converted to penetrating keratoplasty. These two eyes developed keratoconus after acute corneal hydrops.
Conclusion: Compared with the conventional procedure, this new method provides easy, reliable exposure of Descemet’s membrane.
PMCID: PMC1772972  PMID: 16299139
deep lamellar keratoplasty; surgical technique; Descemet’s membrane
6.  Proposal of a new prognostic model for hepatocellular carcinoma: an analysis of 403 patients 
Gut  2005;54(3):419-425.
Background: The prognosis of hepatocellular carcinoma (HCC) is highly dependent on tumour extension and liver function. Recently, two new prognostic scoring systems—the CLIP score, developed by Italian investigators and the BCLC score, developed in Barcelona—have been widely used to assess prognosis in patients presenting with hepatocellular carcinoma. Each system has its own relative limitations.
Aims: To create a new prognostic scoring system which is simple, easy to calculate, and suitable for estimating prognosis during radical treatment of early HCC.
Methods: A total of 403 consecutive patients with HCC treated by percutaneous ablation at the Department of Gastroenterology, University of Tokyo Hospital, between 1990 and 1997 were used as the training sample to identify prognostic factors for our patients and used to develop the Tokyo score. As a testing sample, 203 independent patients who underwent hepatectomy at the Department of Hepato-Biliary-Pancreatic Surgery were studied. Prognostic factors were analysed by univariate and multivariate Cox proportional hazard regression.
Results: The Tokyo score consists of four factors: serum albumin, bilirubin, and size and number of tumours. Five year survival was 78.7%, 62.1%, 40.0%, 27.7%, and 14.3% for Tokyo scores 0, 1, 2, 3, and 4–6, respectively. The discriminatory ability of the Tokyo score was internally validated by bootstrap methods. The Tokyo score, CLIP score, and BCLC staging were compared by Akaike information criterion and Harrell’s c index among training and testing samples. In the testing sample, the predictive ability of the Tokyo score was equal to CLIP and better than BCLC staging.
Conclusions: The Tokyo score is a simple system which provides good prediction of prognosis for Japanese patients with HCC requiring radical therapy.
PMCID: PMC1774402  PMID: 15710994
hepatocellular carcinoma; prognostic score; CLIP score; BCLC staging system; percutaneous ethanol injection therapy; hepatic resection
7.  Altered expression of topoisomerase IIα contributes to cross-resistant to etoposide K562/MX2 cell line by aberrant methylation 
British Journal of Cancer  2005;92(8):1486-1492.
KRN 8602 (MX2) is a novel morpholino anthracycline derivative having the chemical structure 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. To investigate the mechanisms of resistance to MX2, we established an MX2-resistant phenotype (K562/MX2) of the human myelogeneous leukaemia cell line (K562/P), by continuously exposing a suspension culture to increasing concentrations of MX2. K562/MX2 cells were more resistant to MX2 than the parent cells, and also showed cross-resistance to etoposide and doxorubicin. Topoisomerase (Topo) IIα protein levels in K562/MX2 cells were lower of those in K562/P cells on immunoblot analysis and decreased expression of Topo IIα mRNA was seen in K562/MX2 cells. Topoisomerase II catalytic activity was also reduced in the nuclear extracts from K562/MX2 cells when compared with K562/P cells. Aberrant methylated CpG of Topo IIα gene was observed in K562/MX2 cells when compared with the parent line on methylation-specific restriction enzyme analysis. To overcome the drug resistance to MX2 and etoposide, we investigated treatment with 5-Aza-2′-deoxycytidine (5AZ), which is a demethylating agent, in K562/MX2 cells. 5-Aza-2′-deoxycytidine treatment increased Topo IIα mRNA expression in K562/MX2 cells, but not in K562/P cells, and increased the cytotoxicity of MX2 and etoposide. Methylated CpG was decreased in K562/MX2 cells after 5AZ treatment. We concluded that the mechanism of drug resistance to MX2 and etoposide in K562/MX2 cells might be the combination of decreased expression of Topo IIα gene and increased methylation, and that 5AZ could prove to be a novel treatment for etoposide-resistant cell lines, such as K562/MX2.
PMCID: PMC2362017  PMID: 15798770
K562; topoisomerase; MX2; etoposide; methylation
8.  Epidemiology of idiopathic cardiomyopathy in Japan: results from a nationwide survey 
Heart  2002;87(2):126-130.
Objective: To estimate the total number of patients with idiopathic cardiomyopathy in Japan and the prevalence of the disorder.
Design: A nationwide epidemiological survey.
Setting: Hospitals selected randomly from among all hospitals in Japan.
Patients: Patients presenting with any of the three types of idiopathic cardiomyopathy: dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy.
Main outcome measures: The total number of patients in Japan was estimated using the sampling and response rates in each stratum with respect to hospital size. The second survey was conducted for patients reported in the first survey in order to obtain detailed information, including age, sex, and specific clinical data.
Results: Estimated patient totals and 95% confidence intervals (CI) were 17 700 (95% CI 16 500 to 18 800) for dilated cardiomyopathy, 21 900 (95% CI 20 600 to 23 200) for hypertrophic cardiomyopathy, and 300 (95% CI 250 to 350) for restrictive cardiomyopathy. Crude prevalence per 100 000 population was estimated as 14.0 for dilated cardiomyopathy, 17.3 for hypertrophic cardiomyopathy, and 0.2 for restrictive cardiomyopathy; crude incidence per 100 000 person-years was estimated as 3.58, 4.14, and 0.06, respectively.
Conclusions: The total number and prevalence of patients with idiopathic cardiomyopathy in Japan are estimated for the first time in a nationwide survey. The prevalence of dilated cardiomyopathy in Japan appears to be about half that of Western populations, while that of hypertrophic cardiomyopathy is about the same.
PMCID: PMC1766994  PMID: 11796547
cardiomyopathy; epidemiology; Japan
9.  Raised interleukin 6 concentrations as a predictor of postangioplasty restenosis 
Heart  2000;83(5):578.
PMCID: PMC1760823  PMID: 10768914
10.  Phase II study of S-1, a novel oral fluorouracil, in advanced non-small-cell lung cancer 
British Journal of Cancer  2001;85(7):939-943.
The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who had not received previous chemotherapy for advanced disease were enrolled in this study. 59 patients (22 stage IIIB and 37 stage IV) were eligible for the evaluation of efficacy and safety. S-1 was administered orally, twice daily, after meals. 3 dosages of S-1 were prescribed according to body surface area (BSA) so that they would be approximately equivalent to 80 mg m−2day−1: BSA < 1.25 m2, 40 mg b.i.d.; BSA≥1.25 but <1.5 m2; 50 mg b.i.d., and BSA≥1.5 m2: 60 mg b.i.d. One cycle consisted of consecutive administration of S-1 for 28 days followed by a 2-week rest period, and cycles were repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59); (95% confidence interval: 12.3–34.7%). A PR was observed in 22.7% (5/22) of the stage IIIB patients and 21.6% (8/37) of the stage IV patients. The median response duration was 3.4 months (1.1–13.7 months or longer). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). The grade 3 or 4 toxicities consisted of decreased haemoglobin level in 1.7% of patients (1/59), neutropenia in 6.8% (4/59), thrombocytopenia in 1.7% (1/59), anorexia in 10.2% (6/59), diarrhoea in 8.5% (5/59), stomatitis in 1.7% (1/59), and malaise in 6.8% (4/59), and their incidences were relatively low. There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all patients was 10.2 months (95% confidence interval: 7.7–14.5 months), and the one-year survival rate was 41.1%. The MST of the stage IIIB patients was 7.9 months, and that of the stage IV patients was 11.1 months. The one-year survival rates of the stage IIIB and IV patients were 30.7% and 47.4%, respectively. S-1 was considered to be an active single agent against NSCLC. Further study of S-1 with other active agents is warranted. © 2001 Cancer Research Campaign
PMCID: PMC2375091  PMID: 11592762
NSCLC; tegafur; CDHP; S-1
11.  Quantitation of Fas and Fas ligand gene expression in human ovarian, cervical and endometrial carcinomas using real-time quantitative RT-PCR 
British Journal of Cancer  2000;82(10):1682-1688.
Alterations in the expression of Fas (CD95/APO-1) and its ligand (FasL) have been demonstrated in various types of cancers as a mechanism for tumour cell to escape from the immune system. In the present study, we evaluated the expression of the Fas and FasL genes in a wide range of primary gynaecological carcinomas. These included 31 ovarian, 29 cervical and 25 endometrial carcinoma tissues as well as four ovarian and three cervical carcinoma cell lines. Our real-time quantitative reverse transcription polymerase chain reaction analysis revealed that down-regulation of Fas expression is more prominent than the up-regulation of FasL expression in all types of gynaecological cancer studied. This down-regulation of Fas expression was also true for the seven carcinoma cell lines. Only one cervical carcinoma cell line, DoT, exhibited a high level of FasL expression. These results indicated that down-regulation of Fas expression is a common abnormality in many types of cancers including gynaecological cancers, whereas an increase in FasL expression is not a common phenomenon in these cancers. © 2000 Cancer Research Campaign
PMCID: PMC2374514  PMID: 10817504
Fas; FasL; quantitative PCR; primary tumours
12.  Domain organization and functional analysis of Thermus thermophilus MutS protein. 
Nucleic Acids Research  1998;26(18):4153-4159.
MutS protein binds to DNA and specifically recognizes mismatched or small looped out heteroduplex DNA. In order to elucidate its structure-function relationships, the domain structure of Thermus thermophilus MutS protein was studied by performing denaturation experiments and limited proteolysis. The former suggested that T. thermophilus MutS consists of at least three domains with estimated stabilities of 12.3, 22.9 and 30.7 kcal/mol and the latter revealed that it consists of four domains: A1 (N-terminus to residue 130), A2 (131-274), B (275-570) and C (571 to C-terminus). A gel retardation assay indicated that T.thermophilus MutS interacts non-specifically with double-stranded (ds), but not single-stranded DNA. Among the proteolytic fragments, the B domain bound to dsDNA. On the basis of these results we have proposed the domain organization of T. thermophilus MutS and putative roles of these domains.
PMCID: PMC147827  PMID: 9722634
13.  Characterization of a thermostable DNA photolyase from an extremely thermophilic bacterium, Thermus thermophilus HB27. 
Journal of Bacteriology  1997;179(20):6499-6503.
The photolyase gene from Thermus thermophilus was cloned and sequenced. The characteristic absorption and fluorescence spectra of the purified T. thermophilus photolyase suggested that the protein has flavin adenine dinucleotide as a chromophore. The second chromophore binding site was not conserved in T. thermophilus photolyase. The purified enzyme showed light-dependent photoreactivation activity in vitro at 35 and 65 degrees C and was stable when subjected to heat and acidic pH.
PMCID: PMC179569  PMID: 9335302
14.  Two core promotor mutations identified in a hepatitis B virus strain associated with fulminant hepatitis result in enhanced viral replication. 
Journal of Clinical Investigation  1996;98(10):2268-2276.
Viral mutations have been implicated in alteration of the biological phenotype of hepatitis B virus (HBV). We recently cloned and sequenced the viral genome of an HBV strain associated with an outbreak of fulminant hepatitis (FH strain). The FH strain contained numerous mutations in all genomic regions and was functionally characterized by a more efficient encapsidation of pregenomic RNA leading to highly enhanced replication. To define the responsible mutation(s) for the enhanced replication, we introduced individual mutations of the FH strain into a wild-type construct by oligonucleotide-directed mutagenesis. Analysis of viral replication showed that two adjacent mutations in the HBV core promotor (C to T at nucleotide 1768 and T to A at nucleotide 1770) led to high level replication. Similar to the FH strain, this mutant displayed the phenotype of enhanced encapsidation of pregenomic RNA. Functional studies in an encapsidation assay demonstrated that the identified mutations resulted in a minor increase of pregenomic RNA transcription (two- to threefold) and a major transcription-independent enhancement (> 10-fold) of viral encapsidation. Our results demonstrate that the two adjacent mutations in the HBV core promotor region are responsible for the enhanced replication of the FH strain. These two mutations, outside the previously described encapsidation signal, core, and polymerase polypeptides, appeared to affect a novel genetic element involved in viral encapsidation.
PMCID: PMC507676  PMID: 8941643
15.  Distinct gene expression patterns in skeletal and cardiac muscle are dependent on common regulatory sequences in the MLC1/3 locus. 
Molecular and Cellular Biology  1996;16(8):4524-4534.
The myosin light-chain 1/3 locus (MLC1/3) is regulated by two promoters and a downstream enhancer element which produce two protein isoforms in fast skeletal muscle at distinct stages of mouse embryogenesis. We have analyzed the expression of transcripts from the internal MLC3 promoter and determined that it is also expressed in the atria of the heart. Expression from the MLC3 promoter in these striated muscle lineages is differentially regulated during development. In transgenic mice, the MLC3 promoter is responsible for cardiac-specific reporter gene expression while the downstream enhancer augments expression in skeletal muscle. Examination of the methylation status of endogenous and transgenic promoter and enhancer elements indicates that the internal promoter is not regulated in a manner similar to that of the MLC1 promoter or the downstream enhancer. A GATA protein consensus sequence in the proximal MLC3 promoter but not the MLC1 promoter binds with high affinity to GATA-4, a cardiac muscle- and gut-specific transcription factor. Mutation of either the MEF2 or GATA motifs in the MLC3 promoter attenuates its activity in both heart and skeletal muscles, demonstrating that MLC3 expression in these two diverse muscle types is dependent on common regulatory elements.
PMCID: PMC231451  PMID: 8754853
16.  Enhanced replication of a hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. 
Journal of Virology  1994;68(3):1651-1659.
Hepatitis B virus (HBV) mutants unable to synthesize HBV e antigen have been described in association with fulminant hepatitis. We have cloned and sequenced the entire viral genome of an HBV strain associated with an epidemic of fulminant hepatitis. This strain contained, in addition to two G-to-A mutations in the precore region (nucleotides 1898 and 1901), numerous other mutations in conserved nucleotide positions resulting in significant amino acid substitutions in HBV gene products. We introduced either or both of the two G-to-A mutations into wild-type HBV by oligonucleotide-directed mutagenesis and generated replication-competent constructs of these mutants as well as the fulminant strain. Viral antigen synthesis, transcription, and replication were analyzed after transfection into human hepatoma cells. All viral constructs produced and secreted similar levels of envelope proteins (HBV surface antigen). Analysis of cellular lysate for core-specific immunoreactivity demonstrated a much higher level of core-associated antigens in cells transfected with the fulminant strain. While cells transfected with mutant and wild-type HBV DNAs synthesized similar levels of viral RNAs, the fulminant strain directed the synthesis of a much higher level of core-associated replicative intermediates (as well as virion particles) than the wild type and mutants with either or both of the precore mutations. Increase in the encapsidation of pregenomic RNA into core particles likely the basis for the enhanced replication associated with the fulminant strain. Our study suggests that an HBV mutant with enhanced viral replication may be important in the pathogenesis of fulminant hepatic failure, and mutations other than the precore mutations may be responsible for this variant behavior.
PMCID: PMC236623  PMID: 8107226
17.  Hepatitis B virus precore mutation and fulminant hepatitis in the United States. A polymerase chain reaction-based assay for the detection of specific mutation. 
Journal of Clinical Investigation  1994;93(2):550-555.
Hepatitis B virus (HBV) variants with precore mutation(s) resulting in the absence of HBeAg production have been associated with the occurrence of fulminant hepatitis in Japan, Israel, and southern Europe, where the prevalence of this HBV strain appears common. In areas such as United States, where HBV infection is not endemic, the role of this mutant virus in fulminant hepatitis is unknown. We developed an amplification refractory mutation detection system to detect specifically the presence of the G to A mutation at nucleotide position 1898, which is the most frequently observed mutation resulting in a precore stop codon. In addition, this method provided a quantitative measurement of the relative ratio of one strain to the other. Using this system, we tested HBV strains for the presence of the stop codon mutation in sera from 40 cases of fulminant hepatitis B occurring in the United States. Serum HBV DNAs from 28 patients were analyzed successfully. A mixture of wild-type and mutant strains in various ratios were observed in 15 patients, wild type exclusively in 11, and mutant exclusively in 2. Four of these patients had undergone liver transplantation for HBV-associated cirrhosis and developed fulminant HBV-associated hepatitis after transplantation. Pre- and posttransplant serum samples from one patient were analyzed: a mixture of wild-type and mutant HBV strains was detected in both samples. Our study demonstrated that both wild-type and mutant HBV strains are associated with fulminant hepatitis, and that in some patients in the United States, factors other than precore mutations contribute to the development of fulminant hepatitis.
PMCID: PMC293877  PMID: 8113393
18.  MPTP delta, a putative murine homolog of HPTP delta, is expressed in specialized regions of the brain and in the B-cell lineage. 
Molecular and Cellular Biology  1993;13(9):5513-5523.
Protein tyrosine phosphatases (PTPs), together with protein tyrosine kinases (PTKs), are involved in the regulation of cell activation, growth, and differentiation. To further elucidate the fine tuning of cell growth and differentiation through tyrosine phosphorylation, we tried to isolate mouse receptor-type PTP (RPTP) cDNA clones by screening mouse brain cDNA libraries with mouse CD45 PTP domain probes under reduced-stringency conditions. Characterization of isolated cDNA clones for RPTP showed that the cytoplasmic region contains two tandem repeats of PTP domain of about 230 amino acids with intrinsic phosphatase activity. The extracellular region was composed of immunoglobulin (Ig)-like domains and fibronectin type III (FN-III)-like domains. The gene was highly homologous to human PTP delta (HPTP delta) and thus was named MPTP delta (murine counterpart of HPTP delta). The MPTP delta gene appeared to generate at least three species of mRNA, which differ in the composition of the extracellular domain: type A, one Ig-like and four FN-III-like domains; type B, one Ig-like and eight FN-III-like domains; and type C, three Ig-like and eight FN-III-like domains. Interestingly, the 5' untranslated region and the leader peptide of types A and B were completely different from those of type C. Northern (RNA) blot analysis demonstrated that brain, kidney, and heart cells express three mRNA species of about 7 kb. Antibody directed against part of the extracellular domain of type A MPTP delta recognized a 210-kDa protein in brain and kidney lysates. In situ hybridization of brain samples revealed that MPTP delta mRNA is present in the hippocampus, thalamic reticular nucleus, and piriform cortex, where some Src family PTKs have been also demonstrated to exist. Although MPTP delta mRNA was not detected in lymphoid tissues, all of the pre-B-cell lines tested and one of three B-cell lines tested expressed MPTP delta mRNA, whereas antibody-producing B-cell hybridomas and T-cell and macrophage lines did not. Finally, the MPTP delta locus was tightly linked to the brown (b) locus on mouse chromosome 4.
PMCID: PMC360267  PMID: 8355697
19.  A clinico-pathological study of adult histiocytosis X involving the brain. 
Adult histiocytosis X involving the CNS caused progressive spastic paraparesis. The diagnosis was made by immunoreactive anti-S100 protein antibody staining and from the presence of Birbeck granules in biopsy specimens of skin lesions. Neuropathological examination showed massive proliferation and infiltration of S-100 containing histiocyte-like cells and reactive astrocytes throughout the CNS.
PMCID: PMC489739  PMID: 8410024
20.  Targeted transfection and expression of hepatitis B viral DNA in human hepatoma cells. 
Journal of Clinical Investigation  1993;91(3):1241-1246.
A soluble DNA carrier system consisting of an asialoglycoprotein covalently linked to poly-L-lysine was used to bind DNA and deliver hepatitis B virus (HBV) DNA constructs to asialoglycoprotein receptor-positive human hepatoma cells. 4 d after transfection with surface or core gene expression constructs, HBsAg and HBeAg in the media were measured to be 16 ng/ml and 32 U/ml per 10(7) cells, respectively. Antigen production was completely inhibited by the addition of an excess of asialoorosomucoid. On the other hand, asialoglycoprotein receptor-negative human hepatoma cells, SK-Hep1, did not produce any viral antigens under identical conditions after incubation with HBV DNA complexed to a conjugate composed of asialoorosomucoid and poly-L-lysine. Using a complete HBV genome construct, HBsAg and HBeAg levels reached 16 ng/ml and 16 U/ml per 10(7) cells, respectively. Northern blots revealed characteristic HBV RNA transcripts including 3.5-, 2.4-, and 2.1-kb fragments. Intracellular and extracellular HBV DNA sequences including relaxed circular, linear and single stranded forms were detected by Southern blot hybridization. Finally, 42-nm Dane particles purified from the spent cultures medium were visualized by electron microscopy. This study demonstrates that a targetable DNA carrier system can transfect HBV DNA in vitro resulting in the production of complete HBV virions.
PMCID: PMC288084  PMID: 8383700
21.  Characterization of an extracellular protease inhibitor of Bacillus brevis HPD31 and nucleotide sequence of the corresponding gene. 
A novel proteinaceous protease inhibitor was isolated from the culture supernatant of Bacillus brevis HPD31. The protease inhibitor of B. brevis (designated BbrPI) was produced extracellularly in multiple forms having at least three different molecular weights. One of them, BbrPI-a, was purified to near homogeneity and only showed inhibitory activity toward serine proteases, such as trypsin, chymotrypsin, and subtilisin. BbrPI was presumed to form a trypsin-inhibitor complex in a molar ratio of 1:1. The inhibitor was found to be heat resistant at neutral and acidic pHs. The gene coding for BbrPI was cloned into Escherichia coli, and its nucleotide sequence was determined. The sequence suggested that BbrPI is produced with a signal peptide of 24 amino acid residues. The amino acid sequence of the protein deduced from the DNA sequence contained the amino acid sequences of amino termini of the inhibitors, a, b, and c, and their putative precursor determined chemically. The molecular weight of the precursor was about 33,000, and the molecular weights of inhibitors a, b, and c were about 22,000, 23,500, and 24,000, respectively. It is presumed that the secreted precursor protein, which is probably inactive, is cleaved by protease into several active protease inhibitor molecules. BbrPI shows no significant homology to the protease inhibitors described previously and is unique in not having any cysteine residues in its molecule.
PMCID: PMC195279  PMID: 1610177
22.  Alexia with agraphia of kanji (Japanese morphograms). 
The case of the right-handed young Japanese woman with alexia with agraphia of kanji (the Japanese morphograms) due to a small circumscribed haematoma in the left posterior inferior temporal gyrus is described. Her chief complaint was the inability to read and write kanji. Detailed examination showed that her alexia with agraphia was much more predominant for kanji than kana (the Japanese syllabograms). These facts suggest that the processing of kanji and kana involves different intrahemispheric mechanisms.
PMCID: PMC1032342  PMID: 3668562
23.  Production of immunoglobulin M (IgM) autoantibodies to IgG in rabbits inoculated with Mycoplasma salivarium cells grown in medium supplemented with rabbit serum. 
Infection and Immunity  1987;55(1):263-265.
Mycoplasma salivarium cells propagated in PPLO broth (Difco Laboratories, Detroit, Mich.) supplemented with rabbit serum (10% [vol/vol]) and harvested by centrifugation were shown to contain rabbit immunoglobulin G (IgG) (approximately 4 to 10% of total cell proteins) and to produce IgM autoantibodies to IgG when inoculated into rabbits.
PMCID: PMC260313  PMID: 3491790
24.  Lead and zinc concentrations in plasma, erythrocytes, and urine in relation to ALA-D activity after intravenous infusion of Ca-EDTA. 
Lead and zinc concentrations in plasma, erythrocytes, and urine, urinary ALA concentration, and ALA-D activity in blood were studied for four hours in two male lead workers during and after a one hour infusion of Ca-EDTA 2Na. Urinary and plasma lead concentrations increased as a result of administering Ca-EDTA 2Na, and the ratios of lead concentrations in plasma to those in urine were greatly increased. The increase of plasma lead concentration was not due to the haemolytic effect of Ca-EDTA 2Na but was mobilised lead, rapidly excreted in the urine. ALA-D activity in blood increased at the end of the experiment with a transient decrease during the infusion of Ca-EDTA 2Na. As zinc concentrations in erythrocytes and plasma did not decrease during the infusion despite an increase in the urinary excretion of zinc, the transient decrease of ALA-D activity was not due to a loss of zinc caused by Ca-EDTA 2Na. From the results of additional experiments in vitro, this transient decrease could be related neither to Ca-EDTA 2Na nor to lead in the blood.
PMCID: PMC1009289  PMID: 6426500
25.  Drug fever due to oxprenolol. 
British Medical Journal  1980;281(6232):27-28.
PMCID: PMC1713707  PMID: 7407486

Results 1-25 (27)