Spotted and rippled reticulate hypermelanosis: a possible variant of Dowling-Degos disease.
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Biomedical subjects
Publications and source records attributed to H Kobayashi.
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PURPOSE: To assess whether paired pulse magnetic motor evoked potential (MEP) can predict surgical prognosis in patients with intractable epilepsy. METHODS: MEP of the unilateral hand muscles were recorded following paired pulse transcranial magnetic stimulation (TMS) of the motor cortex. The interstimulus intervals of paired stimulation were 1-16 ms with a conditioning stimulus that was 90% active motor threshold. Subjects were six patients with temporal lobe epilepsy (TLE) scheduled for anterior temporal lobectomy and three patients with myoclonic or head-drop seizures scheduled for anterior corpus callosotomy, resulting in the unilateralization of epileptic discharges. The hemisphere showing unilateral discharges was defined as the affected hemisphere. The intracortical inhibition and facilitation curve was drawn based on MEP before and after surgery and the relationship between MEP and surgical prognosis was investigated. RESULTS: In five patients with TLE showing class I surgical results (Engel's classification), the affected hemisphere showing cortical hyperexcitability preoperatively was almost normalized after surgery. However, in a patient with class III, the unaffected hemisphere showed cortical hyperexcitability before and after surgery. In the callosotomy group, two patients with excellent outcomes showed the same results as TLE group with class I. CONCLUSIONS: Paired pulse magnetic MEP may provide predictive value in terms of surgical outcome in those patients with intractable epilepsy.
Under special conditions, a superconducting state where the order parameter oscillates in real space, the so-called FFLO state, is theoretically predicted to exist near the upper critical field, as first proposed by Fulde and Ferrell, and Larkin and Ovchinnikov. We report systematic measurements of the interlayer resistance in high magnetic fields to 45 T in the two-dimensional magnetic-field-induced organic superconductor lambda-(BETS)2FeCl4, where BETS is bis(ethylenedithio)tetraselenafulvalene. The resistance is found to show characteristic dip structures in the superconducting state. The results are consistent with pinning interactions between the vortices penetrating the insulating layers and the order parameter of the FFLO state. This gives strong evidence for an oscillating order parameter in real space.
For successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene glycol) (PEG), which is useful for conferring stability in the systemic circulation, but is undesirable for the cellular uptake and the following processes. We report the development of a PEG-peptide-lipid ternary conjugate (PEG-Peptide-DOPE conjugate (PPD)). In this strategy, the PEG is removed from the carriers via cleavage by a matrix metalloproteinase (MMP), which is specifically expressed in tumor tissues. An in vitro study revealed that the PPD-modified gene carrier (Multifunctional Envelope-type Nano Device: MEND) exhibited pDNA expression activity that was dependent on the MMP expression level in the host cells. In vivo studies further revealed that the PPD was potent in stabilizing MEND in the systemic circulation and facilitating tumor accumulation. Moreover, the i.v. administration of PPD or PEG/PPD dually-modified MEND resulted in the stimulation of pDNA expression in tumor tissue, as compared with a conventional PEG-modified MEND. Thus, MEND modified with PPD is a promising device, which has the potential to make in vivo cancer gene therapy achievable.
We report results of 77Se NMR frequency shift in the normal state of the organic charge-transfer salt kappa-(BETS)2FeBr4 which shows magnetic field-induced superconductivity (FISC). From a simple mean-field analysis, we determined the field and the temperature dependences of the magnetization m(pi) of the pi conduction electrons on BETS molecules. We found that the Fe spins are antiferromagnetically coupled to the pi electrons and determined the exchange field to be J = -2.3T/microB. The exchange field from the fully saturated Fe moments (5 microB) is compensated by an external field of 12 T. This is close to the central field of the FISC phase, consistent with the Jaccarino-Peter local field-compensation mechanism for FISC [Phys. Rev. Lett. 9, 290 (1962)].
A reporter gene assay revealed that promoters derived from Synechococcus PCC7942 (S.7942) psbAI and Synechocystis PCC6803 (S.6803) psbAII were suitable for the expression of foreign ribulose-bisphosphate carboxylase (RuBisCO; EC 4.1.1.39) in S.7942 cells. Transformational vectors with a promoter and a foreign RuBisCO gene, cvrbc originated from Allochromatium vinosum, were constructed on a binary vector, pUC303, and introduced to S.7942 cells. When the cvrbc was expressed with the S.7942 psbAI promoter, the total RuBisCO activity increased 2.5- to 4-fold than that of the wild type cell. The S.6803 psbAII promoter increased the activity of the transformant 1.5-2 times of that of wild type cell. There was a significant increase in the rate of photosynthesis depending on the increase of RuBisCO activity. The maximum rate of photosynthesis of the transformant cell was 1.63 times higher than that of the wild type under the illumination of 400 micromol m(-2) s(-1), at 20 mM bicarbonate and at 30 degrees C. Although the photosynthesis of the higher plant is limited by the ability of photosystems under high irradiance and the high CO(2 )concentration, that of the S.7942 cell is limited by the RuBisCO activity, even at high CO(2) concentrations and under high irradiance.
AIMS: To establish a keratoprosthesis (Kpro) surgical technique that maintains an intact superficial corneal layer. METHODS: A manual microkeratome (Moria LSK-1) was used to create a 130 mum flap of approximately 10 mm diameter in the right eye of Japanese white rabbits. The stoma beneath the flap area was dissected before the removal of a 5.0 mm stromal disc. A 5.0 mm collagen I immobilised poly(vinyl alcohol) (COL-PVA) disc was placed on the exposed posterior stroma close to Descemet's membrane. The flap was repositioned and fixed using 10-0 nylon sutures, which were removed 2 days following surgery. The corneas were followed clinically by slit lamp microscopy and photographs. Rabbits were sacrificed after 6 months, and the transplanted corneas were examined histologically by haematoxylin and eosin staining and immunohistochemistry against vimentin and alpha-smooth muscle actin (alpha-SMA). RESULTS: The transplanted COL-PVA discs remained transparent throughout the study, with no complications related to the flap or overlying epithelium. The interface between COL-PVA and Descemet's membrane remained clear without signs of opacification caused by scarring or cellular deposition. Pathology revealed the intact COL-PVA polymer in the posterior stroma, with minimal cellular infiltration along the anterior and posterior interfaces. Immunohistology shows vimentin and alpha-SMA staining at levels comparable to lamellar keratoplasty control. CONCLUSIONS: Microkeratome assisted deep lamellar keratoprosthesis may be a safe technique for the transplantation of artificial hydrogels for therapeutic purposes.
The autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by diverse mutations in one allele of the gene that encodes the arginine vasopressin (AVP) precursor protein, AVP-neurophysin II (AVP-NP II). Most of the mutations identified so far are located in either the signal peptide or NP II moiety. Two recently published mutations in the AVP gene identified in kindreds with adFNDI predict a substitution of histidine for tyrosine at position 2 and a deletion of phenylalanine at position 3 in AVP. They are unique among adFNDI mutations in that they are the only adFNDI mutations that affect amino acid residues in the AVP moiety of the pro-hormone. Here, we report a novel heterozygous missense mutation in the AVP moiety of the AVP-NP II gene in a Japanese person with neurohypophyseal diabetes insipidus (DI). This mutation occurs at position 2 in AVP and predicts a substitution of serine for tyrosine (Y21S). It is expected to interfere with normal binding of AVP with NP II, and thus result in misfolding of the precursor proteins. The data of this study support the notion that mutations affecting the AVP moiety can result in the initiation of the pathological processes.
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Xanthinoxidase (XO) derived radical species are involved in bacterial translocation (BT) in cholestatic rats. The mechanism by which XO influences remains unclear. It has been shown recently that nuclear factor-kappa B (NF-kappaB), a ubiquitous transcription factor, can be activated by oxidative stress and thereby promote the process of BT. We investigated the effects of NF-kappaB inactivation on the incidence of BT in cholestatic rats. Sprague-Dawley rats were randomly assigned to one of eight groups: groups 1-4 were sham laparotomized rats either untreated (S1) or treated for 5 days with thalidomide (S2), curcumin (S3), or Inchin-ko (ICK; S4); groups 5-8 underwent common bile duct ligation (CBDL) for 5 days and were either untreated (C1) or treated with thalidomide (C2), curcumin (C3), or ICK (C4). After 5 days bacteriological cultures were performed from portal blood and V. cava, from the central mesenteric lymph node complex (MLN), spleen, and liver. The intensity of the activated NF-kappaB-subunit p65/p50 in the ileum mucosa was estimated by light microscopy and a scoring system from 1 to 20. Malondialdehyde (MDA) and myeloperoxidase activity (MPO) in the ileum were evaluated and expressed as U/g dry weight. Thalidomide and ICK reduced in CBDL-rats significantly the BT rate (63% vs. 18%, 63% vs. 30%, P<0.01). Enzyme estimations (MDA, MPO, and GSH) in sham operated animals showed no significant changes in the untreated groups compared with the treated groups. CBDL-rats pre-treatment with all three compounds caused a significant increase of MDA levels if groups were compared with the untreated C1-group (C1 31.6+/-7.7, C2 54.5+/-12.2, C3 53.3+/-11.2, and C4 47.2+/-9.4). GSH was reduced after the pre-treatment by all compounds but only significantly after curcumin pre-treatment (C1 vs. C3: 13.9+/-1.8 vs. 7.1+/-1.8; P<0.05). MPO estimations were significantly higher in the untreated C1-group if compared with groups C2, C3, and C4 (C1 1036.4+/-340.9, C2 709.9+/-125.9, C3 545.2+/-136.6, and C4 556.7+/-247.4; P<0.05). Thalidomide inhibited significantly the activation of NF-kappaB (C2 vs. C1: 6.0+/-4.5 vs. 12.7+/-5.3; P<0.01). Likewise, Curcumin and ICK suppressed NF-kappaB activation, but this did not reach significance in this experiment. NF-kappaB is involved in the process of BT in cholestatic rats and may be activated by XO derived ROS. We assume that the activated NF-kappaB initiates transcription of target genes inducing cytokine production, which in turn disrupts the tight junctions leading to BT from the intestinal lumen to the MLNs and circulation.
We investigated whether insulin resistance is associated with impaired cardiac fatty acid metabolism in maintenance hemodialysis patients without coronary artery disease. We studied 55 nondiabetic (63+/-11 years old) and 51 diabetic (61+/-10 years old) hemodialysis patients with normal coronary arteries, using single-photon emission computed tomography (SPECT) with an iodinated fatty acid analogue, iodine-123-beta-methyl iodophenyl-pentadecanoic acid ((123)I-BMIPP), to evaluate cardiac fatty acid metabolism. SPECT imaging was graded regionally from 0 (normal) to 4 (absence of tracer) to calculate a summed score for 17 left ventricular segments. Insulin resistance was determined using the homeostasis model assessment index of insulin resistance (HOMA-IR). HOMA-IR correlated with summed BMIPP score in nondiabetic and diabetic patients. Stepwise multiple regression analysis showed that HOMA-IR was independently associated with BMIPP summed score in nondiabetic (beta=0.774, t=9.218, P=0.0001) and diabetic patients (beta=0.792, t=9.079, P=0.0001). Left ventricular ejection fraction was lower in nondiabetic subjects with BMIPP summed score of at least 6 plus HOMA-IR of at least 4 than in others with lower values for both assessments (53.1+/-13.8%, n=20 vs 67.7+/-9.1%, n=23, P=0.0002); this was also true in diabetic subjects (50.9+/-15.2%, n=24 vs 71.0+/-13.6%, n=11, P=0.0007). Association between insulin resistance and impaired cardiac fatty acid metabolism may contribute to left ventricular dysfunction in patients with maintenance hemodialysis without coronary diseases.
BACKGROUND: Aceruloplasminaemia is an autosomal recessive disorder caused by specific mutations in the ceruloplasmin gene. Aceruloplasminaemia is clinically characterized by diabetes mellitus, pigment degeneration of the retina, and neurological abnormalities, such as cerebellar ataxia, extrapyramidal signs, and dementia. We present a patient with aceruloplasminaemia who, until progressive neurological abnormalities were noticed, had been treated for more than 30 years as having Type 1 diabetes mellitus requiring multiple insulin injection therapy. CASE REPORT: The patient was a 58-year-old man. At the age of 23 years, he developed diabetes that required multiple insulin injection therapy. At the age of 39 years, he was commenced on continuous subcutaneous insulin infusion (CSII) therapy. Despite CSII therapy, the patient's blood glucose levels were poorly controlled (HbA(1c), approximately 9.5%). He was diagnosed as having aceruloplasminaemia at 58 years of age when he presented with progressive cerebellar ataxia, extrapyramidal signs of recent onset and pigment degeneration of the retina. CONCLUSIONS: It is possible that some diabetic patients with aceruloplasminaemia are mistakenly diagnosed as having Type 1 diabetes mellitus, as they have reduced insulin secretion and develop diabetes at a younger age, before neurological abnormalities associated with aceruloplasminaemia are apparent. Therefore, aceruloplasminaemia should be considered in patients with insulin-dependent diabetes mellitus who develop progressive neurological abnormalities of unknown aetiology along with a microcytic hypochromic anaemia and retinal degeneration.
AIMS: To investigate the requirement of outer membrane porins for osmotic adaptation at alkaline pH in Escherichia coli. METHODS AND RESULTS: Escherichia coli mutants deficient in ompC, ompF and both genes were constructed and the growth of these mutants was observed at alkaline pH. The growth rate of the mutant deficient in both ompC and ompF was slower than that of the wild type and mutants deficient in one of these genes under hyperosmotic stress at pHs above 8.0. The decreased rate was recovered when a cloned ompC was introduced to the mutant, but the growth recovery with a cloned ompF was partial. Such growth diminution was not observed at pHs below 8.0. CONCLUSION: OmpC and OmpF were shown to participate in hyperosmotic adaptation at alkaline pH in E. coli. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report to demonstrate that OmpC and OmpF are required for hyperosmotic adaptation at pHs above 8.0, but not below 8.0.
BACKGROUND: Transforming growth factor (TGF)-beta is a potent multifunctional polypeptide, abundant in the bone matrix. Interleukin (IL)-11 is a pleiotropic cytokine with effects on multiple cell types. The present study was performed to evaluate the regulatory effects of TGF-beta on IL-11 production by human periodontal ligament cells (PDL) and human gingival fibroblasts (HGF). MATERIAL AND METHODS: The expression of TGF-beta receptor in PDL and HGF were observed using flow cytometry. PDL and HGF were stimulated with TGF-beta with or without protein kinase C (PKC) inhibitors and activator. IL-11, bone morphogenetic protein-2 (BMP-2) and TGF-beta mRNA expression was quantified by real-time polymerase chain reaction (PCR). IL-11 production was measured using enzyme-linked immunosorbent assay. RESULTS: PDL and HGF expressed both TGF-beta receptor I and TGF-beta receptor II on the cell surfaces. IL-11 mRNA expression and IL-11 production were augmented by TGF-beta in both PDL and HGF, with higher values in PDL. PKC inhibitors partially suppressed TGF-beta-induced IL-11 production in PDL and HGF, whereas activator enhanced it. TGF-beta mRNA and BMP-2 mRNA expression were up-regulated by TGF-beta in PDL. CONCLUSION: These results suggest that PDL produce IL-11 in response to TGF-beta.
Rhizobium sp. strain NGR234 produces a flavonoid-inducible rhamnose-rich lipopolysaccharide (LPS) that is important for the nodulation of legumes. Many of the genes encoding the rhamnan part of the molecule lie between 87 degrees and 110 degrees of pNGR234a, the symbiotic plasmid of NGR234. Computational methods suggest that 5 of the 12 open reading frames (ORFs) within this arc are involved in synthesis (and subsequent polymerization) of L-rhamnose. Two others probably play roles in the transport of carbohydrates. To evaluate the function of these ORFs, we mutated a number of them and tested the ability of the mutants to nodulate a variety of legumes. At the same time, changes in the production of surface polysaccharides (particularly the rhamnan O antigen) were examined. Deletion of rmlB to wbgA and mutation in fixF abolished rhamnan synthesis. Mutation of y4gM (a member of the ATP-binding cassette transporter family) did not abolish production of the rhamnose-rich LPS but, unexpectedly, the mutant displayed a symbiotic phenotype very similar to that of strains unable to produce the rhamnan O antigen (NGRDeltarmlB-wbgA and NGROmegafixF). At least two flavonoid-inducible regulatory pathways are involved in synthesis of the rhamnan O antigen. Mutation of either pathway reduces rhamnan production. Coordination of rhamnan synthesis with rhizobial release from infection threads is thus part of the symbiotic interaction.
OBJECTIVES: To identify perceived barriers to residents' questioning or challenging their seniors, to determine how these barriers affect decisions, and to assess how these barriers differ across cultures. METHOD: A written questionnaire was administered to residents in teaching hospitals in the US and Japan to assess factors affecting residents' willingness to question or challenge their superiors. The responses were analyzed for statistical significance of differences between the two cultures and to determine the importance of issues affecting decisions. RESULTS: Questionnaires were completed by 175 US and 65 Japanese residents, with an overall response rate of 71%. Trainees from both countries believe that questioning and challenging contribute to safety. The perceived importance of specific beliefs about the workplace differed across cultures in seven out of 22 questions. Residents' decisions to make a challenge were related to the relationships and perceived response of the superiors. There was no statistical difference between the US and Japanese residents in terms of the threshold for challenging their seniors. CONCLUSION: We have identified attributes of residents' beliefs of communication, including several cross-cultural differences in the importance of values and issues affecting one's decision to question or challenge. In contrast, there was no difference in the threshold for challenging seniors by the Japanese and US residents studied. Changes in organizational and professional culture may be as important, if not more so, than national culture to encourage "speaking up". Residents should be encouraged to overcome barriers to challenging, and training programs should foster improved relationships and communication between trainers and trainees.
Imprinted genes in mammals show monoallelic expression dependent on parental origin and are often associated with differentially methylated regions (DMRs). There are two classes of DMR: primary DMRs acquire gamete-specific methylation in either spermatogenesis or oogenesis and maintain the allelic methylation differences throughout development; secondary DMRs establish differential methylation patterns after fertilization. Targeted disruption of some primary DMRs showed that they dictate the allelic expression of nearby imprinted genes and the establishment of the allelic methylation of secondary DMRs. However, how primary DMRs are recognized by the imprinting machinery is unknown. As a step toward elucidating the sequence features of the primary DMRs, we have determined the extents and boundaries of 15 primary mouse DMRs (including 12 maternally methylated and three paternally methylated DMRs) in 12.5-dpc embryos by bisulfite sequencing. We found that the average size of the DMRs was 3.2 kb and that their average G+C content was 54%. Dinucleotide content analysis of the DMR sequences revealed that, although they are generally CpG rich, the paternally methylated DMRs contain less CpGs than the maternally methylated DMRs. Our findings provide a basis for the further characterization of DMRs.
Small salivary phosphoproteins--statherin (ST) and histatin 1 (HT1) - are found in the acquired enamel pellicle which modulates Streptococcus mutans adhesion onto dental enamel. However, their roles in S. mutans adhesion onto enamel surfaces are still undefined. The aim of this study was to investigate whether and how ST and HT1 affect (i) S. mutans adhesion and (ii) the adsorption of S. mutans adhesion-promoting salivary proteins onto hydroxyapatite (HA) in vitro. We fractionated human parotid saliva by adsorption to HA and further by gel filtration chromatography. Adhesion of [3H]-labeled S. mutans strain MT8148 onto sintered HA plates was promoted significantly (>10-fold) by high-molecular weight glycoprotein fraction (HMWGP), but not by purified ST or HT1. More interestingly, promotion of S. mutans adhesion onto HA by HMWGP was significantly reduced by adding purified ST or HT1 to HMWGP. [3H]-labeled S. mutans adhesion on HA was positively correlated to the [14C]-labeled HMWGP adsorption onto HA, which was also reduced by the addition of purified ST and HT1. Synthetic peptides corresponding to ST and HT1 reduced the parotid saliva-promoted S. mutans adhesion. However, removal of the negative charges in the N-terminal domains of ST and HT1 diminished their inhibitory effects on S. mutans adhesion promoted by parotid saliva. We conclude that ST and HT1 competitively inhibit the adsorption of salivary HMWGP, and thereby reduce S. mutans adhesion onto HA surfaces.