Comparing treatments for basal cell carcinoma in terms of long-term treatment-failure: a network meta-analysis.

Although many variations of guidelines have been released, there is limited research that compares multiple treatment strategies for basal cell carcinoma (BCC). The aim of this study was to systematically review the studies reporting on multiple treatments for BCC with systematic review and network meta-analyses. Search formulas for databases, such as PubMed, EMBASE, Web of Science Core Collection and Cochrane Central Register of Controlled Trials, were created with the support of Cochrane Japan. The patient-level and tumour-level meta-analyses were performed for both the long-term treatment-failure and treatment-success. Of the 1464 studies identified from the database and hand searches, 14 met our inclusion criteria. These 14 studies included 2524 patients and 1738 tumours. Our study indicated that the incidence of treatment-failure of invasive treatments such as surgery and Mohs micrographic surgery was significantly lower than that of superficial therapies such as cryotherapy, photodynamic therapy, radiotherapy or topical therapies, in the patient-level and the tumour-level analyses, despite histological-type and pretreatment. Relapse of BCC may be a low life-threatening risk, and there are merits of non-surgical treatment. However, the significant difference in the recurrence rate is essential. Our study can provide useful guidance to clinicians in selecting treatment options for BCC.

Frontal cerebral blood flow change associated with infant-directed speech.

OBJECTIVE: To examine the auditory perception of maternal utterances by neonates using near-infrared spectroscopy (NIRS). METHODS: Twenty full-term, healthy neonates were included in this study. The neonates were tested in their cribs while they slept in a silent room. First, two probe holders were placed on the left and right sides of the forehead over the eyebrows using double-sided adhesive tape. The neonates were then exposed to auditory stimuli in the form of infant-directed speech (IDS) or adult-directed speech (ADS), sampled from each of the mothers, through an external auditory speaker. RESULTS: A 2 (stimulus: IDS and ADS) x 2 (recording site: channel 1 (right side) and channel 2 (left side)) analysis of variance for these relative oxygenated haemoglobin values showed that IDS (Mean = 0.25) increased brain function significantly (F = 3.51) more than ADS (Mean = -0.26). CONCLUSIONS: IDS significantly increased brain function compared with ADS. These results suggest that the emotional tone of maternal utterances could have a role in activating the brains of neonates to attend to the utterances, even while sleeping.

Comparison of in vitro antifungal activities of topical antimycotics launched in 1990s in Japan.

In vitro anti-dermatophyte, anti-Candida albicans and anti-Malassezia furfur activities of amorolfine hydrochloride (AMF), terbinafine hydrochloride (TBF), butenafine hydrochloride (BTF), neticonazole hydrochloride (NCZ) and ketoconazole (KCZ), all of which were introduced for the treatment of dermatomycoses in the 1990s in Japan, were compared. Although all of the test drugs are classified as an ergosterol biosynthesis inhibitor, the antifungal properties were found to be different. TBF and BTF exerted extremely potent antifungal activity against Trichophyton spp. but not against C. albicans and M. furfur, whilst KCZ and NCZ showed potent antifungal activity against C. albicans and M. furfur rather than Trichophyton spp. AMF exhibited potent antifungal activity against all of the fungal species tested. Fungicidal activities of these antifungal agents against T. rubrum were determined by using neutral red staining. The fungicidal potentialities correlated with those obtained in the in vitro susceptibility test as determined by MICs against dermatophytes. TBF, BTF and AMF exerted more potent fungicidal action than NCZ and KCZ.

HTLV-1 p12(I) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells.

The p12(I) protein, encoded by the pX open reading frame I of the human T-lymphotropic virus type 1 (HTLV-1), is a hydrophobic protein that localizes to the endoplasmic reticulum and the Golgi. Although p12(I) contains 4 minimal proline-rich, src homology 3-binding motifs (PXXP), a characteristic commonly found in proteins involved in signaling pathways, it has not been known whether p12(I) has a role in modulating intracellular signaling pathways. This study demonstrated that p12(I) binds to the cytoplasmic domain of the interleukin-2 receptor (IL-2R) beta chain that is involved in the recruitment of the Jak1 and Jak3 kinases. As a result of this interaction, p12(I) increases signal transducers and activators of transcription 5 (STAT5) DNA binding and transcriptional activity and this effect depends on the presence of both IL-2R beta and gamma(c) chains and Jak3. Transduction of primary human peripheral blood mononuclear cells (PBMCs) with a human immunodeficiency virus type 1-based retroviral vector expressing p12(I) also resulted in increased STAT5 phosphorylation and DNA binding. However, p12(I) could increase proliferation of human PBMCs only after stimulation of T-cell receptors by treatment of cells with low concentrations of alphaCD3 and alphaCD28 antibodies. In addition, the proliferative advantage of p12(I)-transduced PBMCs was evident mainly at low concentrations of IL-2. Together, these data indicate that p12(I) may confer a proliferative advantage on HTLV-1-infected cells in the presence of suboptimal antigen stimulation and that this event may account for the clonal proliferation of infected T cells in vivo. (Blood. 2001;98:823-829)

Environmental hyperthermic infant and early childhood death: circumstances, pathologic changes, and manner of death.

Infant and early childhood death caused by environmental hyperthermia (fatal heat stroke) is a rare event, typically occurring in vehicles or beds. The aims of this study were to describe the demographics, circumstances, pathology, and manner of death in infants and young children who died of environmental hyperthermia and to compare these cases with those reported in the literature. Scene investigation, autopsy reports, and the microscopic slides of cases from three jurisdictions were reviewed. The subjects in 10 identified cases ranged in age from 53 days to 9 years. Eight were discovered in vehicles and 2 in beds. When the authors' cases were grouped with reported cases, the profile of those in vehicles differed from those in beds. The former were older, were exposed to rapidly reached higher temperatures, and often had more severe skin damage. The latter were mostly infants and were exposed to lower environmental temperatures. Hepatocellular necrosis and disseminated intravascular coagulation were reported in victims who survived at least 6 hours after the hyperthermic exposure. The consistent postmortem finding among nearly all victims was intrathoracic petechiae, suggesting terminal gasping in an attempt at autoresuscitation before death. The manner of death was either accident or homicide. Recommendations for the scene investigation are made.

Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction.

The lats gene has been identified as a tumour suppressor in Drosophila melanogaster using mosaic screens. Mosaic flies carrying somatic cells that are mutant for lats develop large tumours in many organs. The human LATS1 homologue rescues embryonic lethality and inhibits tumour growth in lats mutant flies, demonstrating the functional conservation of this gene. Biochemical and genetic analyses have revealed that LATS1 functions as a negative regulator of CDC2 (ref. 3). These data suggest that mammalian LATS1 may have a role in tumorigenesis. To elucidate the function of mammalian LATS1, we have generated Lats1-/- mice. Lats1-/- animals exhibit a lack of mammary gland development, infertility and growth retardation. Accompanying these defects are hyperplastic changes in the pituitary and decreased serum hormone levels. The reproductive hormone defects of Lats1-/- mice are reminiscent of isolated LH-hypogonadotropic hypogonadism and corpus luteum insufficiency in humans. Furthermore, Lats1-/- mice develop soft-tissue sarcomas and ovarian stromal cell tumours and are highly sensitive to carcinogenic treatments. Our data demonstrate a role for Lats1 in mammalian tumorigenesis and specific endocrine dysfunction.

Molecular cloning of a novel sex pheromone responsible for the release of a different sex pheromone in Closterium peracerosum-strigosum-littorale complex.

A sex pheromone, protoplast-release-inducing protein (PR-IP) inducer, of the Closterium peracerosum-strigosum-littorale complex is known to induce the release of PR-IP, from mating-type plus (mt+) cells during sexual reproduction. The purified PR-IP inducer was treated with trypsin to obtain internal peptides for determination of partial amino acid sequences. Using these sequences, oligonucleotides were synthesized and used as primers for the combined reverse transcription-PCR. A 296 bp cDNA fragment was amplified, permitting the cloning of corresponding full length cDNA (CpPI; Closterium peracerosum-strigosum-littorale complex PR-IP inducer). The deduced amino acid sequence of CpPI encodes a protein of 212 amino acid residues of M(r) 23,071 whereas portion of the peptide secreted is predicted to have 142 amino acid residues of M(r) 15,717 and shows no significant similarity with known proteins. The predicted protein has three possible consensus sequences for asparagine-linked glycosylation site. The CpPI gene was expressed when mating-type minus (mt-) cells were incubated at a low cell density in the light. Nitrogen deprivation from the medium enhances expression of the CpPI gene. An analysis by genomic Southern hybridization revealed that the cDNA probe hybridized to several DNA fragments obtained from both the genome of mt- and mt+ cells. However, in mt- cells, transcripts for the PR-IP inducer could not be detected by Northern hybridization.

Deletion of the Wilson's disease gene in hereditary hepatitis LEC rats.

LEC rats develop disorder of cooper metabolism and hepatitis similar to those of human Wilson's disease. We recently demonstrated that the gene responsible for hepatitis (hts) of LEC rats is homologous to Wilson's disease gene (WD). The present study showed a deletion of at least 90 base pair of WD cDNA in LEC rats, which corresponds to nucleotides 3981 to 4071 in human WD cDNA sequence. This deletion was linked with hepatic copper accumulation and hepatitis, and considered to be a primary mutation for hepatic disorder in the LEC rat. The WD gene was assigned to rat chromosome 16 at band q12.2-q12.4 by fluorescence in situ hybridization (FISH).

Peroxidation of lipids and growth inhibition induced by UV-B irradiation.

Cotyledons excised from dark-grown seedlings of cucumber (Cucumis sativus L.) were cultured in vitro under UV radiation at different wavelengths, obtained by passage of light through cut-off filters with different transmittance properties. Growth and the synthesis of chlorophyll (Chl) in cotyledons were inhibited and malondialdehyde was accumulated upon irradiation at wavelengths below 320 nm. Exogenous application of scavengers of free radicals reversed the growth inhibition induced by UV-B. Measurement of the fluorescence of Chl a suggested that electron transfer in photosystems was affected by UV-B irradiation. On the basis of these results, the involvement is postulated of active species of oxygen in damages to thylakoid membranes and the growth inhibition that are induced by UV-B irradiation.

[Casting accuracy and shrinkage of titanium castings made with zirconia investments].

To obtain inlay, crown and bridge types of titanium castings with sufficient size accuracy, zirconia investments with 10 mol % calcia were studied for their setting expansion, thermal expansion, total expansion, casting shrinkage compensation deficiency on fabrication method, particle size of zirconia, calcia and mixing liquid. Addition of calcia caused the change from contraction to expansion in setting and the additional thermal expansion at 900-1,200 degrees C. The choice of calcia and mixing liquid makes great influence on setting expansion, which is grouped into saturation type and delayed expansion type. By the use of the saturation type, total expansion could be controlled in the range of -2-(+)3%. Titanium castings of inlay, crown, bridge types with the values -2-(+)2% of casting shrinkage compensation deficiency could be successfully obtained. The casting shrinkage of titanium was estimated as 1.8-2%. The castings have the surface with a metallic brilliance as cast.

[Effect of addition of calcia on the properties of zirconia investments].

The zirconia investments with calcia were studied of the compressive strength, setting expansion, thermal expansion, total expansion, thermogravitometry, differential thermal analysis on fabrication method, concentration, particle size of zirconia, calcia and mixing liquid. Addition of calcia caused the change from contraction to expansion in setting expansion. The optimum concentration of calcia was determined to be 10 mol% as judged from total expansion, strength and operability.

[Development of dental quick casting with zircon-phosphoric acid investments].

The application of zircon (ZrSiO4) that has high refractoriness, high thermal conductivity and a low coefficient of thermal expansion, to quick casting investment was studied. Various zircon powders and phosphoric acid solutions were tested with respect to the higher thermal shock resistance. The formulation and properties of zircon-phosphoric acid investment materials such as water/powder ratio, fluidity of slurry, setting time, setting expansion, thermal expansion, thermal analysis, green and fired compressive strength were measured. Formulation of zircon slurry for coating was zircon flower #600 30%, zircon flower #350 10%, and zircon sand CP 60%, and that for sanding was zircon flower #200. The mixing liquid was 15% phosphoric acid and liquid/powder ratio was 0.1. The slurry using phosphoric acid had good fluidity and good workability. The 24-hour green strength was 1 MPa, fired strength was 10 MPa, 24-hour setting expansion was -0.04% and the thermal expansion at 1000 degrees C was 0.31%. Immediately after coating with zircon slurry, the coating layer was dried, sintered and dewaxed by thermal shock. The thermal shock consisted of the following four-step manipulations. The first is hot air drying (50 degrees C, 5 minutes), the second is heat shock (900 degrees C, 3 seconds), the third is redrying (220 degrees C, 3 minutes) and the fourth is dewaxing (550 degrees C, 3 minutes). Small casting of pure titanium and K-metal could be done successfully by the quick casting method using the zircon-phosphoric acid investments. It was found that the total expansion of the secondary investments influenced the casting adapatability.

Another fatal case involving hydroxyzine.

Blood and tissue concentrations of hydroxyzine, an antihistamine with sedative properties, were determined in a fatal case of accidental hydroxyzine ingestion. Hydroxyzine was extracted at alkaline pH and analyzed by gas chromatography.

Modification of the anticodon triplet of E.coli tRNAMetf by replacement with trimers complementary to non-sense codons UAG and UAA.

E. coli tRNAMetf was hydrolyzed with RNase A using a limited amount of the enzyme to give two half molecules lacking the anticodon trimer and 3'-terminal dimer. Chemically synthesized trimers CUAp and UUAp were joined to the 5'-half molecules by phosphorylation with polynucleotide kinase plus ATP followed by treatment with RNA ligase. These modified tRNAMetf species had anticodons complementary to the termination codons UAG and UAA. Two half fragments were joined by a similar procedure to yield a molecule lacking the anticodon trimer and the 3'-dimer. Methionine acceptor activity of these tRNA was tested under conditions in which the CAU inserted control tRNAMetf accepted methionine. It was found that all three modified molecules were not recognized by the methionyl-tRNA synthetase from E.coli. The other sixteen amino acids were not incorporated with partially purified aminoacyl-tRNA synthetases.

Sudden Infant Death Syndrome: a biochemical profile of postmortem vitreous humor.

Postmortem chemical analysis of vitreous humor from Sudden Infant Death Syndrome (SIDS) infants was done. The results were compared to a pediatric control group. The concentrations of potassium, calcium, phosphorus, glutamic oxaloacetic transaminase, glutamic pyruvate transaminase, creatinine phosphokinase, and lactate dehydrogenase were all significantly different from the pediatric control group. Thus it appears that SIDS infants are a different population from the pediatric control group.

Total synthesis of a RNA molecule with sequence identical to that of Escherichia coli formylmethionine tRNA.

A RNA molecule has been synthesized that is identical in sequence to Escherichia coli tRNAfMet except that it lacks the base modifications present in the E. coli tRNA. This was achieved by enzymatic joining of chemically synthesized oligonucleotides with chain lengths of 3-10 which were synthesized by the phosphodiester or phosphotriester method. First, quarter molecules of tRNA were constructed by joining of chemically synthesized fragments with RNA ligase. The 5'-quarter molecule (bases 1-20) served as an acceptor in joining reactions with the 3',5'-bisphosphorylated donor molecule (bases 21-34). The 5'-half molecule thus obtained was treated with phosphatase and joined to the 3'-half molecule which was prepared by ligation of the other quarter molecules (bases 35-60, acceptor; bases 61-77, donor) followed by 5'-phosphorylation with polynucleotide kinase. The synthetic tRNA was characterized by oligonucleotide pattern and was partially active in aminoacylation with E. coli methionyl-tRNA synthetase.

Synthesis of 5' fragments of formylmethionine transfer ribonucleic acid and their reconstitution with a natural three-quarter molecule.

An eicosanucleotide C--G--C--G--G--G--G--U--G--G--A--G--C--A--G--C--C--U--G--Gp corresponding to the bases 1--20 of the nascent sequence for the Escherichia coli tRNAfMet has been synthesized by the joining of the chemically synthesized oligonucleotides C--G--C--G, G--G--G--U--G--G and A--G--C--A--G--C--C--U--G--Gp using RNA ligase from T4-infected E. coli. The hexanucleotide and decanucleotide were phosphorylated with polynucleotide kinase and [gamma-32P]ATP prior to the joining reactions. The decanucleotide and eicosanucleotide were reconstituted respectively with the 3'-three-quarter molecule obtained by limited digestion with RNase T1 of the natural tRNAfMet from E. coli and the activity of the complex as a methionine acceptor was tested using purified methionyl-tRNA synthetase from E. coli. The amino acid acceptor activity of the reconstituted molecules was 11% and 84% with respect to that of the intact tRNAfMet.

Total synthesis of tRNAfMet.

Oligonucleotides corresponding to the E. coli tRNAfMet fragments and their analogs have been synthesized by the phosphodiester or phosphotriester method. The nascent fragments were joined by using RNA ligase to yield a total tRNA molecule. The synthetic molecule was tested its ability to accept methionine in the presence of purified methionyl-tRNA synthetase from E. coli. The charged tRNA and the hydrolyzed methionine were isolated by gel filtration. The discharged tRNA was characterized by nearest neighbor analysis and 5'-end analysis.