Transient Hyperintensity of the Infant Thyroid Gland on T1-Weighted MR Imaging: Correlation with Postnatal Age, Gestational Age, and Signal Intensity of the Pituitary Gland.

BACKGROUND AND PURPOSE: The signal intensity of the thyroid in neonates is high on T1WI. It is affected by gestational and postnatal ages. However, the extent of the influence of these ages is unknown. This study investigated the relationship of signal intensities of the infant thyroid with postnatal and gestational ages and anterior pituitary using 3D gradient-echo T1WI. MATERIALS AND METHODS: This retrospective study included 183 T1-weighted images from 181 infants. Using a multiple linear regression analysis, we evaluated the effects of postnatal and gestational ages on the thyroid-muscle signal intensity ratio. The relationship between the thyroid and anterior pituitary signal intensities on T1WI and the age of the infants was evaluated. RESULTS: Multiple linear regression analysis showed that the thyroid signal intensity was affected negatively by postnatal age at examination and positively by gestational age at birth (P < .01 and P = .04, respectively). According to the standardized partial regression coefficients, the influence of postnatal age at examination was stronger than that of gestational age at birth (-0.72 and 0.13, respectively). The thyroid and anterior pituitary signal intensities reached constant values at 12 weeks' postnatal age, and the mean thyroid-anterior pituitary signal intensity ratios were almost 1 throughout the entire period. CONCLUSIONS: The signal intensity of the infant thyroid on T1WI was more strongly influenced by the postnatal age at examination than the gestational age at birth, and it was almost equal to that of the anterior pituitary.

Primary bone adult T cell lymphoma with multiple skeletal lesions and debilitating painful osteolysis: a case report.

There have been only a limited number of reports on primary adult T cell lymphoma/leukemia (ATL) in the bone. This is a case report of a 75-year-old patient initially reporting multiple bone pains that were attributed to osteolytic ATL. The patient developed spontaneous chest/back pain and visited a local hospital. Laboratory tests showed high levels of alkaline phosphatase (ALP), and computed tomography (CT) revealed skeletal lesions with osteolysis. Although multiple myeloma was initially suspected, the results of bone marrow aspiration and bone biopsy were inconsistent. After he was referred to our hospital, mild hypercalcemia (10.4 mg/dL) with low-normal intact parathyroid hormone (PTH) (27 pg/mL), low parathyroid hormone-related protein (PTHrP), and elevated 1,25-dihydroxy vitamin D (1,25OH2D) levels (136 pg/mL) narrowed the differential diagnosis down to lymphomatous and granulomatous diseases, and then, the high serum soluble IL-2 receptor (3,450 U/mL) and the flower cells recognized in the peripheral blood sample suggested the involvement of ATL. Finally, the reevaluation of the iliac bone biopsy sample led us to the histological diagnosis of ATL infiltration in the bone. The subsequent two courses of chemotherapy in addition to denosumab resulted in an objective partial metabolic response indicated in 18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Although very rare, the bone involvement of ATL could be used for the differential diagnosis for local osteolytic bone pain in addition to multiple myeloma and metastatic bone diseases.

Impact of Number of Drug Types on Clinical Outcome in Patients with Acute Hip Fracture.

OBJECTIVES: This study aims to investigate the impact of the number of drug types on clinical outcomes for patients with acute hip fracture. DESIGNS: This is a retrospective cross-sectional study. SETTING: A hospital-based database constructed by the Japan Medical Data Center. PARTICIPANTS: Consecutive patients exhibiting acute hip fractures on admission between April 2014 and November 2017 were included. MEASUREMENTS: Relationships among the numbers of varying drug types of ≥6 and ≤5 as well as clinical outcomes were analyzed in 11,073 patients aged ≥65 years. The primary outcome was defined as the Barthel Index efficiency, with the secondary outcome being the length of hospital stay. RESULTS: Median Barthel Index scores at admission and discharge were 5 (interquartile range: 5-20) and 50 (interquartile range: 20-85). The Barthel Index efficiency was significantly higher in the group having received 5 or fewer drug variations taken (1.45 ± 1.77) than in the group receiving 6 or more drug types taken (0.94 ± 1.18) during hospital stays (p < 0.001). The length of hospital stay was significantly shorter in the group receiving 5 or fewer drug types taken (29.9 ± 23.8) than in the group having 6 or more drug types taken (44.3 ± 30.3) during hospital stays (p < 0.001), with the latter number being independently associated with the Barthel Index efficiency and length of hospital stay. CONCLUSIONS: Number of drug types of 6 or more were associated with lower Barthel Index efficiency and longer lengths of hospital stays.

Fabrication of arrays of tapered silicon micro-/nano-pillars by metal-assisted chemical etching and anisotropic wet etching.

Fabrication of a 2D square lattice array of intentionally tapered micro-/nano-silicon pillars by metal-assisted chemical etching (MACE) of silicon wafers is reported. The pillars are square rod shaped with the cross-sections in the range 0.2 × 0.2-0.9 × 0.9 µm2 and heights 3-7 µm. The spacing between pillars in the 2D square lattice was controlled between 0.5 and 3.0 µm. While the pillars after MACE had the high aspect ratio ∼1:5, subsequent anisotropic wet etching in potassium hydroxide solution led to 80°-89.5° tapers with smooth sidewalls. The resulting taper angle showed the relation with geometry of pillar structures; the spacing 0.5-3.0 µm led to the tapering angle 89.5°-80° for 3 and 5 µm tall pillars but 7 µm tall pillars showed no dependency between the tapering angle and the inter-pillar spacing. Such an array of silicon tapered-rods with smooth sidewalls is expected to be applicable as a mold in nanoimprinting applications.

Fetal developmental change in topographical relationship between the human lateral pterygoid muscle and buccal nerve.

In adults, the lateral pterygoid muscle (LPM) is usually divided into the upper and lower heads, between which the buccal nerve passes. Using sagittal or horizontal sections of 14 fetuses and seven embryos (five specimens at approximately 20-25 weeks; five at 14-16 weeks; four at 8 weeks; seven at 6-7 weeks), we examined the topographical relationship between the LPM and the buccal nerve. In large fetuses later than 15 weeks, the upper head of the LPM was clearly discriminated from the lower head. However, the upper head was much smaller than the lower head in the smaller fetuses. Thus, in the latter, the upper head was better described as an 'anterior slip' extending from the lower head or the major muscle mass to the anterior side of the buccal nerve. The postero-anterior nerve course seemed to be determined by a branch to the temporalis muscle (i.e. the anterior deep temporal nerve). At 8 weeks, the buccal nerve passed through the roof of the small, fan-like LPM. At 6-7 weeks, the LPM anlage was embedded between the temporobuccal nerve trunk and the inferior alveolar nerve. Therefore, parts of the LPM were likely to 'leak' out of slits between the origins of the mandibular nerve branches at 7-8 weeks, and seemed to grow in size during weeks 14-20 and extend anterosuperiorly along the infratemporal surface of the prominently developing greater wing of the sphenoid bone. Consequently, the topographical relationship between the LPM and the buccal nerve appeared to 'change' during fetal development due to delayed development of the upper head.

Overexpression and gene amplification of BAG-1L in hormone-refractory prostate cancer.

BAG-1L (Bcl-2-associated anthanogene 1) has been found to interact with androgen receptor (AR), and has been suggested to be involved in the development of prostate cancer. In order to determine the presence of genetic and/or expression alterations of BAG-1L in prostate cancer, we analysed human prostate cancer cell lines and xenografts as well as patient samples of untreated, hormone-naïve, and hormone-refractory prostate carcinomas for sequence variations using denaturing high-performance liquid chromatography (DHPLC), for gene copy number using fluorescence in situ hybridization (FISH), and for expression using both quantitative RT-PCR and immunostaining. Only one sequence variation was found in all 37 cell lines and xenografts analysed. BAG-1 gene amplification was detected in two xenografts. In addition, gene amplification was found in 6 of 81 (7.4%) hormone-refractory clinical tumours, whereas no amplification was found in any of the 130 untreated tumours analysed. Additionally, gain of the BAG-1 gene was observed in 27.2% of the hormone-refractory tumours and in 18.5% of the untreated carcinomas. In a set of 263 patient samples, BAG-1L protein expression was significantly higher in hormone-refractory tumours than in primary tumours (p = 0.002). Altogether, these data suggest that amplification and overexpression of BAG-1L may be involved in the progression of prostate cancer.

Photo-oxidation of biodegraded crude oil and toxicity of the photo-oxidized products.

We investigated the physicochemical changes resulting from irradiation by sunlight of biodegraded crude oil. An Arabian light crude oil sample was first subjected to microbial degradation. n-Alkanes and aromatic compounds such as naphthalenes, fluorenes, dibenzothiophenes and phenanthrenes possessing short, alkyl side chain(s) were almost completely degraded, while the contents of the saturated and aromatic fractions were reduced by 70% and 40%, respectively. This biodegraded oil was then suspended in seawater and exposed to sunlight irradiation for several weeks. The most remarkable change caused by the irradiation was a substantial decline in the aromatic fraction with a concomitant increase in the resin and asphaltene fractions. A 13C-nuclear magnetic resonance (NMR) spectroscopic analysis showed that the aromaticity of the biodegraded oil was significantly lower in the irradiated sample. A field desorption-mass spectrometric (FD-MS) analysis showed that sunlight irradiation reduced the average molecular weight of the oil components and formed oxygenated compounds. Consistent with this observation is that the oxygen content in the oil increased as the irradiation was prolonged. The bioavailability of the biodegraded oil was increased by the photo-oxidation: the growth of seawater microbes was minimal when the non-irradiated biodegraded oil was used as the source of carbon and energy; however, growth was significant when irradiated biodegraded oil was used. The concentration of dissolved organic carbon (DOC) increased linearly during the sunlight irradiation of the biodegraded oil, and this increase was matched by an increase in ultraviolet-absorptive materials in the seawater. The photochemically formed, water-soluble fraction (WSF) showed acute toxicity against the halophilic crustacean, Artemia.

Protective effect of neurotropin against lipopolysaccharide-induced hypotension and lethality linked to suppression of inducible nitric oxide synthase induction.

Neurotropin is a non-protein extract from the dermis of rabbits inoculated with vaccinia virus and has been clinically used as an analgesic in Japan. We present in the current report evidence for its potential therapeutic value against endotoxin shock. Administration of this compound prior to lipopolysaccharide (LPS) challenge resulted in a reversal of a decrease of the mean arterial pressure in rats and also amelioration of lethality in mice. Anti-inducible nitric oxide synthase (iNOS) Western blotting of tissue extracts from LPS-treated mice revealed almost complete suppression of iNOS induction by Neurotropin. The findings in vivo were reproduced in in vitro experiments in which cultured human umbilical vascular endothelial cells were challenged with LPS. Simultaneous treatment of the cells with Neurotropin resulted in complete suppression of iNOS induction and significant reduction of cell death. These results suggested a therapeutic value of Neurotropin in the treatment of endotoxin shock that was linked, at least in part, to suppression of iNOS induction and reduced cell damage in vascular endothelial cells.

A Web-based home helper support system.

A web-based "Home Helper" support system has been developed for improving scheduling and record keeping efficiency and for eliminating unnecessary travel. This support system consists of a wireless internet mobile phone for each "Home Helper" and a server at the main office. After each visit, the Home Helpers send their care reports via the mobile phone to the office server. This server computer then creates the "filings" automatically and in appropriate format for insurance and government use.

Katanosin B and plusbacin A(3), inhibitors of peptidoglycan synthesis in methicillin-resistant Staphylococcus aureus.

Both katanosin B and plusbacin A(3) are naturally occurring cyclic depsipeptide antibiotics containing a lactone linkage. They showed strong antibacterial activity against methicillin-resistant Staphylococcus aureus and VanA-type vancomycin-resistant enterococci, with MICs ranging from 0.39 to 3.13 microg/ml, as well as against other gram-positive bacteria. They inhibited the incorporation of N-acetylglucosamine, a precursor of cell wall synthesis, into peptidoglycan of S. aureus whole cells at concentrations close to their MICs. In vitro studies with a wall-membrane particulate fraction of S. aureus showed that katanosin B and plusbacin A(3) inhibited the formation of lipid intermediates, with 50% inhibitory concentrations (IC(50)s) of 2.2 and 2.3 microg/ml, respectively, and inhibited the formation of nascent peptidoglycan, with IC(50)s of 0.8 and 0.4 microg/ml, respectively. Vancomycin, a well-known inhibitor of transglycosylation, did not inhibit the formation of lipid intermediates but did inhibit the formation of nascent peptidoglycan, with an IC(50) of 4.1 microg/ml. Acetyl-Lys-D-Ala-D-Ala, an analog of the terminus of the lipid intermediates, effectively suppressed the inhibition of transglycosylation by vancomycin, but did not suppress those by katanosin B and plusbacin A(3). These results indicate that the antibacterial activity of katanosin B and plusbacin A(3) is due to blocking of transglycosylation and its foregoing steps of cell wall peptidoglycan synthesis via a mechanism differing from that of vancomycin.

Directionality of DNA replication fork movement strongly affects the generation of spontaneous mutations in Escherichia coli.

Using a pair of plasmids carrying the rpsL target sequence in different orientations to the replication origin, we analyzed a large number of forward mutations generated in wild-type and mismatch-repair deficient (MMR(-)) Escherichia coli cells to assess the effects of directionality of replication-fork movement on spontaneous mutagenesis and the generation of replication error. All classes of the mutations found in wild-type cells but not MMR(-) cells were strongly affected by the directionality of replication fork movement. It also appeared that the directionality of replication-fork movement governs the directionality of sequence substitution mutagenesis, which occurred in wild-type cells at a frequency comparable to base substitutions and single-base frameshift mutations. A very strong orientation-dependent hot-spot site for single-base frameshift mutations was discovered and demonstrated to be caused by the same process involved in sequence substitution mutagenesis. It is surprising that dnaE173, a potent mutator mutation specific for sequence substitution as well as single-base frameshift, did not enhance the frequency of the hot-spot frameshift mutation. Furthermore, the frequency of the hot-spot frameshift mutation was unchanged in the MMR(-) strain, whereas the mutHLS-dependent mismatch repair system efficiently suppressed the generation of single-base frameshift mutations. These results suggested that the hot-spot frameshift mutagenesis might be initiated at a particular location containing a DNA lesion, and thereby produce a premutagenic replication intermediate resistant to MMR. Significant numbers of spontaneous single-base frameshift mutations are probably caused by similar mechanisms.

Preclinical in vivo antitumor efficacy of nedaplatin with gemcitabine against human lung cancer.

The antitumor efficacy of the combination of nedaplatin (NDP) with gemcitabine (GEM) was evaluated. We also compared the antitumor activity of NDP plus GEM with that of cisplatin (CDDP) plus GEM or carboplatin (CBDCA) plus GEM. Ma44, which is a human lung cancer sensitive to GEM, and NCI-H460, which is a human lung cancer refractory to GEM, were used in this study. GEM was injected i.v. once followed by i.v. injection of NDP at an interval of approximately 30 min into tumor-bearing athymic mice. GEM was administered again 3 or 4 days thereafter. Combined dosing of NDP with GEM resulted in synergistically enhanced inhibition of tumor growth in the Ma44 tumor model. NDP plus GEM was also effective against Ma44 cells when given late in the therapy, a model for advanced disease. Potent augmentation of growth inhibition by NDP with GEM was also found with the NCI-H460 tumor model. The combination effect of NDP plus GEM appeared to be superior to that of CDDP plus GEM or CBDCA plus GEM in both tumor models. Toxicity in terms of blood cell numbers was not enhanced by the combination of NDP with GEM. These results suggest the effectiveness of combination of NDP with GEM for clinical therapy.

Spontaneous loss of heterozygosity in diploid Saccharomyces cerevisiae cells.

To obtain a broad perspective of the events leading to spontaneous loss of heterozygosity (LOH), we have characterized the genetic alterations that functionally inactivated the URA3 marker hemizygously or heterozygously situated either on chromosome III or chromosome V in diploid Saccharomyces cerevisiae cells. Analysis of chromosome structure in a large number of LOH clones by pulsed-field gel electrophoresis and PCR showed that chromosome loss, allelic recombination, and chromosome aberration were the major classes of genetic alterations leading to LOH. The frequencies of chromosome loss and chromosome aberration were significantly affected when the marker was located in different chromosomes, suggesting that chromosome-specific elements may affect the processes that led to these alterations. Aberrant-sized chromosomes were detected readily in approximately 8% of LOH events when the URA3 marker was placed in chromosome III. Molecular mechanisms underlying the chromosome aberrations were further investigated by studying the fate of two other genetic markers on chromosome III. Chromosome aberration caused by intrachromosomal rearrangements was predominantly due to a deletion between the MAT and HMR loci that occurred at a frequency of 3.1 x 10(-6). Another type of chromosome aberration, which occurred at a frequency slightly higher than that of the intrachromosomal deletion, appeared to be caused by interchromosomal rearrangement, including unequal crossing over between homologous chromatids and translocation with another chromosome.

All-artery multigraft coronary artery bypass grafting with only internal thoracic arteries possible and safe: a randomized trial.

BACKGROUND: The internal thoracic artery (ITA) bypass to the left anterior descending coronary artery is of proven benefit in multigraft coronary artery bypass. Total ITA grafts, if reoperation is averted by avoiding saphenous vein grafts (SVGs), are attractive. The safety of the total ITA graft operation (all-ITA) is a concern. METHODS: A randomized trial of multiple-ITA bypass graftings with the use of bilateral sequential ITA without SVGs was performed. Control patients received 1 ITA plus SVG. Inclusion criteria were those used in the Coronary Artery Surgery Study, extended to age 76 years, and any angina class, except emergent. One hundred sixty-two patients were randomized (81 patients per group) from January 1, 1990, to December 31, 1994. RESULTS: Baseline traits were similar as were cross-clamp times, pump times, and number of arteries bypassed (average, 4.3 arteries). Patients who received multiple ITA grafts had no myocardial infarctions, per reference laboratory. One patient died, and 2 patients returned for bleeding. The ITA-SVG group had similar results. The all-ITA group experienced successful completion in 93% of cases. Complications did not differ from control patients. CONCLUSIONS: Early and 5-year outcomes were not different between the all-ITA group and the ITA with SVGs group. We believe experienced surgeons can safely extend the ITA to multibypass coronary artery bypass without use of SVG to achieve an all-ITA operation.

Two DNA polymerases of Escherichia coli display distinct misinsertion specificities for 2-hydroxy-dATP during DNA synthesis.

The insertion specificities of an oxidized dATP analogue, 2-hydroxydeoxyadenosine 5'-triphosphate (2-OH-dATP), were determined using the alpha (catalytic) subunit of Escherichia coli DNA polymerase III and the exonuclease-deficient Klenow fragment of DNA polymerase I. In contrast to our previous observation that mammalian DNA polymerase alpha incorporated the oxidized nucleotide opposite T and C, these two E. coli DNA polymerases incorporated 2-OH-dATP opposite T and G on the DNA template. Steady-state kinetic studies indicated that the alpha subunit incorporated 2-OH-dATP 10 times more frequently opposite T than opposite G. On the other hand, the incorporation of 2-OH-dATP opposite T by the exonuclease-deficient Klenow fragment was 2 orders of magnitude more efficient than that opposite G. These results indicate that the misinsertion specificity of 2-OH-dATP differs between replicative and repair-type DNA polymerases, and provide a biochemical basis for the mutations induced by 2-OH-dATP in E. coli.

Epstein-Barr virus-associated lymphoproliferative disease after a cord blood transplant for Diamond-Blackfan anemia.

A 7-year-old boy with Diamond-Blackfan anemia (DBA) developed lymphoproliferative disease (LPD) after a cord blood transplant (CBT). 3.1 x 107/kg mononuclear cells from an HLA one-locus mismatched CB were transplanted after conditioning with total body irradiation (8 Gy), cyclophosphamide (200 mg/kg) and antithymocyte globulin (10 mg/kg). Complete engraftment occurred on day 33 post transplant. Despite the resolution of grade II graft-versus-host disease (GVHD), he died of lymphoma on day 130 post transplant. The tumor was of donor origin, indicating clonal proliferation of Epstein-Barr virus (EBV)-infected B cells. This is the first report of EBV-LPD after CBT. Post-transplant LPD can be a serious EBV-associated complication of CB grafts. Bone Marrow Transplantation (2000) 25, 209-212.

Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor.

The anti-metastatic efficacy and safety of a newly-developed matrix metalloproteinase (MMP) inhibitor were examined. MMI-166, a N-sulfonylamino acid derivative, inhibited the enzyme activity of MMP-2, 9, and 14 but not MMP-1, 3 or 7. Daily oral administration of MMI-166 resulted in potent inhibition of metastatic lung colonization of Lewis lung carcinoma injected via the tail vein and liver metastasis of C-1H human colon cancer implanted into the spleen at inhibition levels of 43% and 63%, respectively. Daily administration of MMI-166 also resulted in prolonged survival of mice given intraperitoneal implantation of Ma44 human lung cancer cells. The anti-metastatic activity of MMI-166 was as effective as that of other MMP inhibitors with broad inhibitory spectrum. MMI-166 did not affect in vitro tumor cell growth. Neither body weight losses nor hematotoxicity was observed during long-term treatment, indicating the safety of MMI-166 in mice. These results indicate that the selective MMP inhibitor MMI-166 has therapeutic potential as an anti-metastasis agent.

An infant with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation.

Here we report a case with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation. A 7-month-old Japanese boy was diagnosed to have NK cell leukemia based on the existence of abnormal cells in the bone marrow with the phenotype of CD3(-) /CD4(+) /CD7(-) /CD8(-) /CD16(-) /CD33(+) /CD34(-) /CD56(+) /HLA-DR(+) /NKB1(+) / CD94(+). The leukemic cells showed few azurophilic granules in the cytoplasm and weak cytotoxic activity. Although he presented with a huge mass occupying the bilateral paranasal sinuses and hepatosplenomegaly, he achieved complete remission by the conventional chemotherapeutic regimen for acute myelogenous leukemia, followed by an unrelated cord blood transplantation. He has remained in complete remission for 14 months posttransplant. To our knowledge, this is the youngest reported case with precursor NK cell leukemia; cord blood transplantation may thus be the treatment of choice for this disease.

Strand asymmetry of +1 frameshift mutagenesis at a homopolymeric run by DNA polymerase III holoenzyme of Escherichia coli.

We have recently shown that single-base frameshifts were predominant among mutations induced within the rpsL target sequence upon oriC plasmid DNA replication in vitro. We found that the occurrence of +1 frameshifts at a run of 6 residues of dA/dT could be increased proportionally by increasing the concentration of dATP present in the in vitro replication. Using single-stranded circular DNA containing either the coding sequence of the rpsL gene or its complementary sequence, the +1 frameshift mutagenesis by DNA polymerase III holoenzyme of Escherichia coli was extensively examined. A(6) --> A(7) frameshifts occurred 30 to 90 times more frequently during DNA synthesis with the noncoding sequence (dT tract) template than with the coding sequence (dA tract). Excess dATP enhanced the occurrence of +1 frameshifts during DNA synthesis with the dT tract template, but no other dNTPs showed such an effect. In the presence of 0.1 mM dATP, the A(6) --> A(7) mutagenesis with the dT tract template was not inhibited by 1.5 mM dCTP, which is complementary to the residue immediately upstream of the dT tract. These results strongly suggested that the A(6) --> A(7) frameshift mutagenesis possesses an asymmetric strand nature and that slippage errors leading to the +1 frameshift are made during chain elongation within the tract rather than by misincorporation of nucleotides opposite residues next to the tract.