Dermoscopic features of pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a disease characterized by aberrant mineralization of soft tissue and fragmentation of elastic fibres. It is often difficult to distinguish PXE clinically from pseudoxanthoma elasticum-like papillary dermal elastolysis (PXE-like PDE). However, we have identified that the dermoscopic findings in PXE include coalescing and reticulated yellow-white clods on a light purple-red background, whereas the dermoscopic findings in PXE-like PDE lack such a coloured background. To our knowledge, this is the first detailed description of dermoscopic differences between PXE and PXE-like PDE.

Relationship between xerostomia and psychotropic drugs in patients with schizophrenia: evaluation using an oral moisture meter.

WHAT IS KNOWN AND OBJECTIVE: Patients with schizophrenia are most commonly treated with antipsychotic medications, often with the addition of anxiolytics. This study used an oral moisture meter to evaluate xerostomia in patients with schizophrenia taking typical and atypical antipsychotics, anxiolytics and non-psychotropic medications. METHODS: Patients diagnosed with schizophrenia according to ICD-10 criteria in the Department of Psychiatry, Kitasato University East, and affiliated hospitals were studied. All patients were on psychotropic medications. Patients with diseases associated with xerostomia, such as Sjögren's syndrome I, were excluded. RESULTS AND DISCUSSION: A total of 127 patients were enrolled. Mean oral moisture was 27·81 ± 2·27% (normal, ≥30·0%). A significant association was observed between objective oral moisture and the subjective sense of dry mouth. Multivariate analysis revealed a negative correlation between the number of antipsychotics and, especially, anxiolytics, and the degree of oral moisture. Drug dosages themselves were not significantly correlated with dry mouth. These findings suggest that objective oral moisture measurements show decreased moisture in patients on these medications and that the degree of moisture shows a greater negative correlation with the number, as opposed to the dosages, of psychotropic drugs administered. WHAT IS NEW AND CONCLUSIONS: When patients with schizophrenia visit a dental clinic, it is important for the dentist to accurately assess the degree of oral moisture and to determine the medications being taken. Based on these findings of the association of polypharmacy with xerostomia, dentists are encouraged to inform the psychiatrist of the need to actively manage patients' xerostomia.

Genetic epidemiology of tooth agenesis in Japan: a population- and family-based study.

Tooth agenesis is one of the most common congenital anomalies in humans. However, the etiology of tooth agenesis remains largely unclear, as well as evidence base useful for genetic counseling. Therefore, we estimated the prevalence and sibling recurrence risk, and investigated agenetic patterns systematically. Tooth agenesis was classified into two subtypes: hypodontia (one to five missing teeth) and oligodontia (six or more missing teeth). The prevalence of these two subtypes were 6.8% [95% confidence interval (CI): 6.1-7.7%] and 0.1% (95% CI: 0.04-0.3%), respectively, and sibling recurrence risk of these were 24.5% (95% CI: 13.8-38.3%) and 43.8% (95% CI: 26.4-62.3%), respectively. This result suggests that the severe phenotype, oligodontia, might be mostly transmitted in a dominant fashion. Using a simple statistical modeling approach, our data were found to be consistent with a bilateral symmetry model, meaning that there was equal probability of missing teeth from the right and left sides.

Comprehensive diagnostic ability of endocytoscopy compared with biopsy for colorectal neoplasms: a prospective randomized noninferiority trial.

BACKGROUND AND STUDY AIMS: Endocytoscopy enables observation at 450-fold magnification during gastrointestinal endoscopy, allowing on-site "optical biopsy." We compared the accuracies of endocytoscopy and standard biopsy for the diagnosis of colorectal neoplasms. PATIENTS AND METHODS: We performed a randomized, controlled, open-label trial of patients with colorectal lesions (≥ 5 mm) detected during colonoscopy in a tertiary referral center. We randomly assigned the 203 detected lesions of 170 eligible patients to either the endocytoscopy or standard biopsy group. An on-site endoscopist assessed the histopathology of the endocytoscopy group lesions according to the endocytoscopic findings, whereas a pathologist later assessed standard biopsy group lesions by microscopic examination of the biopsy specimens. We calculated the diagnostic accuracies in both groups with reference to the final histopathology of the resected specimens. The primary endpoint was to determine whether the diagnostic accuracy of endocytoscopy for neoplastic lesions was noninferior to that of standard biopsy (with a predefined noninferiority margin of 10%). Analyses were by intention-to-treat and per-protocol. The study is registered, number UMIN000003923. RESULTS: Overall, 102 lesions in the endocytoscopy group and 101 in the standard biopsy group were available for primary outcome analysis. There were no complications. The diagnostic accuracy of endocytoscopy for the discrimination of neoplastic lesions was 94.1% (95% confidence interval 87.6% to 97.8%), whereas that of standard biopsy was 96.0% (90.2% to 98.9%), which is within the noninferiority margin (absolute difference -1.9%, -8.6% to +5.0%). CONCLUSIONS: Endocytoscopy is noninferior to standard biopsy for the discrimination of neoplastic lesions. With its advantage of providing an on-site diagnosis, endocytoscopy could provide a novel alternative to standard biopsy in routine colonoscopy.

Impact of the lateral skeletal stability following bilateral sagittal split ramus osteotomy for mandibular asymmetry.

This study evaluated the stability of bilateral sagittal split ramus osteotomy (BSSRO) associated with positional plagiocephaly and temporal and masseter muscles using posteroanterior cephalogram analysis and three-dimensional computed tomography (3D-CT). This retrospective cohort study included 31 patients who underwent BSSRO for mandibular asymmetry. The cranial vault asymmetry index (CVAI) and the cephalic index were used as indicators of positional plagiocephaly. The distance from the vertical reference line to the menton (Me) was measured on posteroanterior cephalograms immediately and 1 year after surgery, and postoperative stability was assessed. Temporal and masseter muscles were constructed from 3D-CT data and their volumes were measured. Simple regression analysis showed a significant correlation between postoperative changes in the vertical reference line to the Me and the CVAI (R = 0.56, p = 0.001), the amount of surgical movement in the vertical reference line to the Me (R = 0.41, p = 0.023), and the variable temporal muscle volume (R = 0.27, p = 0.028). There was no significant correlation between postoperative changes in the vertical reference line to the Me and the cephalic index (R = 0.093, p = 0.62) and variable masseter muscle volume (R = 0.16, p = 0.38). According to multivariate analysis, CVAI (p = 0.003) and amount of surgical movement in the vertical reference line to the Me (p = 0.014) were significant predictors of postoperative change in the vertical reference line to the Me. Positional plagiocephaly and amount of surgical movement influence lateral skeletal stability following BSSRO for mandibular asymmetry.

Patients achieving clearance of HCV with interferon therapy recover from decreased retinol-binding protein 4 levels.

Retinol-binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the blood in several insulin-resistant states. We investigated the association between plasma RBP4 and histological and biochemical characteristics of chronic hepatitis C (CHC), as well as changes in RBP4 levels following interferon therapy. Eighty-one patients with CHC infected with genotype 1 received treatment with peginterferon plus ribavirin. Histological data were available for 41 out of 81 patients before treatment, and the degree of fibrosis, inflammation and steatosis was assessed. Plasma levels of RBP4 were determined in serial samples (before, at the end of treatment, and at 6 months post-treatment). RBP4 levels were lower in CHC patients than in control subjects (34.6 +/- 12.3 microg/mL vs 46.2 +/- 10.5 microg/mL; P

Collagen content and architecture of the puboischiofemoralis muscle in male chicks and broilers with different growth rates on various nutritional planes.

1. Various growth rates of chickens were induced with different nutritional regimes, and the collagen content and architecture of the medial part of the puboischiofemoralis muscle were compared among 21-d-old chicks and 80- or 95-d-old broilers. 2. The percentage muscle weight relative to live weight increased from chicks to 80-d-old broilers and the 95-d-old broilers attained the largest percentage. An inter-relationship of the percentage muscle weight and the growth rates of birds could not be determined. 3. Collagen concentration was related to the growth rates for the first 21 d post hatching and maintained the same level during the later stages up to 80 d. The 95-d-old broilers, that were subjected to early rapid growth followed by restricted later growth, had the highest collagen content. 4. On SEM (Scanning Electron Microscopy) photographs, endomysial honeycombs were small and encircled by perimysia of a collagen network with small mesh size. Thin and thick perimysia were distinguished and the expanded portion of thick perimysia was also observed. Generally, the perimysia were made up of rough collagen tissue where fatty tissue developed, especially in the broilers. 5. Perimysial collagen fibres with mainly transverse striation were divided into two fundamental types, wide collagen platelets and narrow cords. With growth from the chick to broiler stage, features of the collagen fibres did not change regardless of expansion of the thick perimysia. Endomysia increased slightly from thin to thick meshwork as growth progressed. However, the collagen architecture of the muscle in broilers did not change under different nutritional regimes. 6. In conclusion, the puboischiofemoralis muscle of chickens develops relative to live weight when later growth is limited in broilers, but the collagen architecture is not affected by the different growth rates.

Collagen content and architecture of the Iliotibialis lateralis muscle in male chicks and broilers with different growth rates fed on different nutritional planes.

1. Varying growth rates in chickens were induced by different nutritional regimes. The collagen content and architecture of iliotibialis lateralis (ITL) muscle were compared among 21-d-old chick types and broiler types at 80 or 95 d of age. 2. Relative size of ITL muscle was greater in the rapid growing (1.16% of live weight) than the slow growing chicks (1.02% of live weight). The 80-d-old broilers with a compensatory growth phase after an earlier slow growth period produced ITL muscle at 1.65-1.69% of live weight. The ITL muscle in 80- and 95-d-old broilers with restricted later growth after an earlier rapid growth period was 1.29 and 1.49% of live weight, respectively. 3. Collagen content of ITL muscle did not differ between chick types and also among the broiler types. However, collagen concentration decreased from 6.00-6.51 mg/g in the chicks to 3.33-4.00 mg/g in the broilers. 4. Thick and thin perimysia and honeycomb endomysia were viewed by scanning electron microscope (SEM) photography. In the perimysia, a central wide layer of longitudinal collagen fibres and peripheral narrow band of transverse fibres were distinguished. Collagen baskets of adipocytes were observed in the perimysia. 5. Perimysial collagen fibres markedly increased in number and formed a larger fibre cluster during growth from chicks to broilers. Endomysia changed from thin to thicker meshwork with growth. However, the collagen architecture of the muscle in broilers did not change under different nutritional regimes. 6. In conclusion, ITL muscle of chicken develops optimally when body growth is enhanced, but the collagen content and architecture in broilers are not affected by different growth processes.

Three-dimensional finite element model to predict patterns of pterygomaxillary dysjunction during Le Fort I osteotomy.

The aim of this study was to determine whether non-linear three-dimensional finite element analysis (3D-FEA) can be applied to simulate pterygomaxillary dysjunction during Le Fort I osteotomy (LFI) not involving a curved osteotome (LFI-non-COSep), and to predict potential changes in the fracture pattern associated with extending the cutting line. Computed tomography (CT) image data (100 snapshots) after LFI were converted to 3D-CT images. 3D-FEA models were built using preoperative CT matrix data and used to simulate pterygomaxillary dysjunction. The pterygomaxillary dysjunction patterns predicted by the 3D-FEA models of pterygomaxillary dysjunction were classified into three categories and compared to the pterygomaxillary dysjunction patterns observed in the postoperative 3D-CT images. Extension of the cutting line was also simulated using the 3D-FEA models to predict the risk and position of pterygoid process fracture. The rate of agreement between the predicted pterygomaxillary dysjunction patterns and those observed in the postoperative 3D-CT images was 87.0% (κ coefficient 0.79). The predicted incidence of pterygoid process fracture was higher for cutting lines that extended to the pterygomaxillary junction than for conventional cutting lines (odds ratio 4.75; P<0.0001). 3D-FEA can be used to predict pterygomaxillary dysjunction patterns during LFI-non-COSep and provides useful information for selecting safer procedures during LFI-non-COSep.

Heat radiosensitization and the level of DNA polymerases alpha and beta of human colony-forming unit-granulocyte-macrophage and myeloid leukemias sensitive and resistant to chemotherapeutic agents.

In these studies, heat radiosensitization in normal human colony-forming unit-granulocyte-macrophage (CFU-GM) and several different leukemic cell lines sensitive or resistant to chemotherapeutic agents were measured. Extent of heat radiosensitization was then correlated with the level of DNA polymerases alpha and beta in control and heat-shocked cells in order to examine whether there is a positive correlation between the degree of heat radiosensitization and the level of these enzymes. Our results show that human bone marrow CFU-GM have an x-ray response with D0 of 1.56 Gy and a small amount of heat radiosensitization with a thermal enhancement ratio (TER) of 1.2. K562, a human erythroleukemic cell, showed a D0 of 1.32 +/- 0.2 Gy and TER of 1.4. However, in contrast to normal CFU-GM which showed no shoulder in the X-ray survival curve, K562 cells showed a small shoulder with a quasi-threshold dose, (Dq) of 2 Gy and n of 2. K562 cells resistant to chemotherapeutic drugs such as 1-beta-D-arabinofuranosylcytosine and etoposide (VP-16) showed D0 of 1.47 +/- 0.13, and 1.77 +/- 0.18 Gy; Dq of 4 and 0 Gy; and n of 5 and 1; and TER of 1.6 and 2, respectively. The level of DNA polymerases alpha and beta activity and their respective mRNA levels were approximately the same in all cells. The reduction in the level of DNA polymerase beta after heat treatment however, correlated with the TER obtained for various leukemic cells. These studies indicate that normal CFU-GM and variety of human leukemic cells show only a small amount of heat radiosensitization. However, drug-resistant leukemic cells show a higher amount of heat radiosensitization than their drug-sensitive parent line. This suggests that hyperthermia may be beneficial in eradicating drug-resistant leukemic cells when combined with X-ray. Furthermore, the inactivation of DNA polymerase beta activity results in a higher amount of heat radiosensitization.

Detection of drug resistance in human tumors by in vitro enzymatic amplification.

Both acquired and natural resistance to chemotherapy agents have proved problematic in the treatment of neoplasia. Thymidylate synthase, which catalyzes the synthesis of thymidine precursors, has been shown to be amplified in response to a variety of chemotherapeutic agents. The detection of such amplification could prove beneficial in the development of alternative clinical protocols. In this study we report the use of existing enzymatic amplification methods in order to detect incipient amplification of the thymidylate synthase gene upon resistance to cisplatin. The assay utilizes a modification of the polymerase chain reaction in which a sequence of the thymidylate synthase gene is amplified including two flanking oligonucleotides acting as primers for DNA synthesis. This method exhibits greater sensitivity than conventional nucleic acid detection methods and requires less than 100 ng of total RNA from patient tumors and no in vitro culturing of patient cells.

Structure model of core proteins in photosystem I inferred from the comparison with those in photosystem II and bacteria; an application of principal component analysis to detect the similar regions between distantly related families of proteins.

A principal component analysis based on the physico-chemical properties of amino acid residues is developed to assign similar regions between distantly related families of proteins, taking account of the species diversities in respective families. The most important advantage of this analysis should be that it reflects different physico-chemical properties and thus can predict more detailed structural properties, including the transmembrane helices, than the hydropathy analysis. Its first application reconfirms the similarity between the core proteins of photosynthetic reaction center in purple bacteria and those of photosystem II, indicating that the low percentage of identical amino acid residues estimated previously between them is due to much allowance for amino acid substitutions in purple bacteria. The application of this analysis to the core proteins of photosystem I reveals that any of these proteins includes two domains, each showing high similarity to the amino acid sequences of core proteins in photosystem II and purple bacteria. A core structure model of A1 and A2 proteins folded into four layers of sheets of transmembrane helices is proposed to provide a molecular basis for the electron pathway suggested by spectroscopic experiments as well as for the interaction sites with plastocyanin, 9 kDa protein and LHC proteins.

Levofloxacin- versus metronidazole-based rescue therapy for H. pylori infection in Japan.

BACKGROUND: The ideal second-line treatment regimens for Helicobacter pylori infection may differ between the areas, countries and races. AIM: The aim was to confirm which was the better regimen for second-line therapy after treatment failure with a standard triple therapy in Japan, a high dosage of levofloxacin- or metronidazole-based therapy. PATIENTS: Sixty outpatients with persistent H. pylori infection after a standard triple therapy were enrolled in this prospective, open-label and randomised trial. METHODS: The subjects were randomly administered levofloxacin (300 mg b.d.)- or metronidazole (500 mg b.d.)-based therapy with lansoprazole (30 mg b.d.) and amoxicillin (1000 mg b.d.) for 7 days, and the cure rates and side effects were analysed. Antimicrobial susceptibility was also examined before second-line therapy using the E-test. RESULTS: Good compliance was obtained without severe side effects in both the groups except for two patients. The cure rates, expressed as intention-to-treat and per-protocol analyses, respectively, were 70.0 and 72.4% in the levofloxacin group, and 96.7 and 100% in the metronidazole group. Each regimen often overcame even clarithromycin-resistant strains. CONCLUSION: Metronidazole-based triple therapy is recommended as second-line therapy in Japan, and levofloxacin-based therapy can be an alternative treatment option.

DNA-dependent protein kinase activity correlates with Ku70 expression and radiation sensitivity in esophageal cancer cell lines.

We investigated the relationship between DNA-dependent protein kinase (DNA-PK) activity and radiation sensitivity using 14 esophageal cancer cell lines, TE 1-14. DNA-PK activities differed significantly among the cell lines. The highest DNA-PK activity observed in TE-8 was more than two times higher than the lowest DNA-PK activity observed in TE-5. Significant correlation was observed between DNA-PK activity and D0 (r = 0.766; P = 0.0008). Western blots analysis revealed a significant correlation between DNA-PK activity and Ku70 expression, suggesting that the regulation in DNA-PK activity was associated with Ku70 expression. The data suggest that the measurement of DNA-PK activity and/or Ku70 expression may provide a useful way to predict radiation sensitivity.

Novel biological response modifiers: phthalimides with tumor necrosis factor-alpha production-regulating activity.

Novel N-substituted phthalimides (2-substituted 1H-isoindole-1,3-diones) were prepared, and their effects on tumor necrosis factor-alpha (TNF-alpha) production by human leukemia cell line HL-60 stimulated with 12-O-tetradecanoylphorbol 13-acetate (TPA) or okadaic acid (OA) were examined. A structure-activity relationship study of the N-phenylphthalimides and N-benzylphthalimides revealed that their enhancing effect on TPA-induced TNF-alpha production by HL-60 cells and their inhibiting effect on OA-induced TNF-alpha production by HL-60 cells are only partially correlated.

Expression of variant dihydrofolate reductase with decreased binding affinity to antifolates in MOLT-3 human leukemia cell lines resistant to trimetrexate.

Various alterations of the dihydrofolate reductase (DHFR) gene are involved in resistance. In order to understand the mechanism that induce such gene alterations in human leukemia cells, we studied the expression products of DHFR gene in trimetrexate (TMQ)- and/or methotrexate (MTX)-resistant sublines derived from a MOLT-3 human leukemia cell line. A 200-fold TMQ-resistant subline (MOLT-3/TMQ200) expressed the mutated DHFR mRNA, with a base change (T-->C) at the second position of codon 31, as well as the wild type gene. A MTX-resistant subline derived from MOLT-3/TMQ200 (MOLT-3/TMQ200-MTX500) showed a further increase in the expression of the mutated DHFR mRNA, compared to MOLT-3/TMQ200, with a marked decrease of expression of the wild type DHFR mRNA, which is confirmation of amplification of the mutated DHFR gene. By contrast, a 10,000-fold MTX-resistant subline (MOLT-3/MTX10,000) over-expressed the wild type DHFR mRNA, which is confirmation of amplification of the wild type gene. Increased levels of the DHFR enzyme in these sublines were proportional to expression levels of the DHFR mRNA. The DHFR enzyme expressed in MOLT-3/TMQ200-MTX500 cells showed a 40-fold increase in the Ki values for both MTX and TMQ, compared with values for the wild type DHFR expressed in both MOLT-3/MTX10,000 and its parent cell line. These findings suggest that the altered DHFR gene, which was introduced in MOLT-3 cells by exposure to TMQ, gave rise to a variant enzyme with reduced affinity to antifolates, and that complex DHFR alterations confer drug-resistant phenotypes in antifolate-resistance. Structural difference between the antifolates could be important in the introduction of the differential DHFR gene alterations in the antifolate resistance.

Effect of verapamil on the class I major histocompatibility complex antigen expression in K562 chronic myelogenous leukemia cells treated with recombinant human interferon-gamma.

The effects of various compounds which modulated the intracellular signal transduction on the induction of class I major histocompatibility complex (MHC) antigens by recombinant human interferon-gamma (rIFN-gamma) were investigated using K562, chronic myelogenous leukemia cells. Class I or class II MHC antigens were not expressed in untreated K562 cells and rIFN-gamma (600 units/ml) weakly induced class I antigens on the cells. Among the compounds tested, verapamil but not the calcium ionophore A23187 enhanced the rIFN-gamma-induced class I antigen expression at both the surface molecule and mRNA levels and enhancement by verapamil occurred in a dose-dependent manner at non-toxic concentrations examined (approximately 50 microM). Verapamil alone had no inducible effect on MHC antigen expression. Deprivation of Ca2+ in culture medium by ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) could not cause an enhancement of class I antigen induction by rIFN-gamma. Simultaneous exposure of K562 cells to rIFN-gamma (600 units/ml) and recombinant human tumor necrosis factor (rTNF; 1000 units/ml) in combination with verapamil (50 microM) resulted in a further increase of class I antigens in the cells. The expressions of c-myc oncogene in K562 cells were not changed when the cells were treated with rIFN-gamma (600 units/ml) or verapamil (50 microM), either alone or in combination. These results indicate that verapamil synergistically interacts with rIFN-gamma on the class I antigen induction in K562 cells irrespective of c-myc gene expression and that class I antigen induction in this cell line may not be relevant to calcium influx triggered by IFN-gamma.