CD11c(+) macrophages and levels of TNF-α and MMP-3 are increased in synovial and adipose tissues of osteoarthritic mice with hyperlipidaemia.

To understand more clearly the link between osteoarthritis and hyperlipidaemia, we investigated the inflammatory macrophage subsets and macrophage-regulated matrix metalloprotease-3 (MMP-3) and A disintegrin and metalloprotease with thrombospondin motifs-4 (ADAMTS4) in synovial (ST) and adipose tissues (AT) of osteoarthritic mice with hyperlipidaemia (STR/Ort). CD11c(+) F4/80(+) CD11b(+) macrophage populations in the ST and AT of 9-month-old STR/Ort and C57BL/6J mice were characterized and compared by flow cytometry and real-time polymerase chain reaction (PCR) analyses. Expression of tumour necrosis factor (TNF)-α, MMP-3 and ADAMTS4, and the response of these factors to anionic liposomal clodronate induced-macrophage depletion were also evaluated by real-time PCR. Expression of TNF-α in CD11c(+) cells, which were isolated by magnetic beads, was compared to CD11c(-) cells. In addition, the effect of TNF-α on cultured synovial fibroblasts and adipocytes was investigated. CD11c(+) F4/80(+) CD11b(+) macrophages were increased in ST and AT of STR/Ort mice. The CD11c(+) cell fraction highly expressed TNF-α. Expression of TNF-α and MMP3 was increased in ST and AT, and was decreased upon macrophage depletion. TNF-α treatment of cultured synovial fibroblasts and adipocytes markedly up-regulated MMP-3. CD11c(+) F4/80(+) CD11b(+) macrophages were identified as a common inflammatory subset in the AT and ST of STR/Ort mice with hyperlipidaemia. The induction of inflammation in AT and ST may be part of a common mechanism that regulates MMP3 expression through TNF-α. Our findings suggest that increased numbers of CD11c(+) macrophages and elevated levels of TNF-α and MMP-3 in AT and ST may explain the relationship between hyperlipidaemia and OA.

Neutron-scattering measurement of incommensurate short-range order in single crystals of the S=1 triangular antiferromagnet NiGa(2)S(4).

Neutron scattering is used to investigate spin correlations in ultrapure single crystals of the S=1 triangular lattice NiGa(2)S(4). Despite a Curie-Weiss temperature of Θ(CW)=-80(2) K, static (τ>1 ns) short-range (ξ(ab)=26(3) Å) incommensurate order prevails for T>1.5 K. The incommensurate modulation Q(0)=(0.155(3),0.155(3),0), Θ(CW), and the spin-wave velocity (c=4400 m/s) can be accounted for by antiferromagnetic third-nearest-neighbor interactions J(3)=2.8(6) meV and ferromagnetic nearest-neighbor coupling J(1)=-0.35(9) J(3). Interplane correlations are limited to nearest neighbors and weakened by an in-plane field. These observations show that the short-range ordered glassy phase that has been observed in a number of highly degenerate systems can persist near the clean limit.

Cigarette smoking, CYP1A1 MspI and GSTM1 genotypes, and colorectal adenomas.

Cigarette smoking has been related to increased risk of colorectal adenomas, but the underlying mechanisms are unknown. Genetic polymorphisms are known for enzymes involved in the activation of polycyclic aromatic hydrocarbons and other tobacco-related carcinogens. Polycyclic aromatic hydrocarbons are activated by cytochrome P4501A1 (CYP1A1) and detoxified by glutathione S-transferases. We investigated the relation of CYP1A1 MspI and GSTM1 genotypes to the risk of colorectal adenomas with special reference to interaction with cigarette smoking among 205 cases of colorectal adenomas and 220 controls with normal total colonoscopy in a male Japanese population. Cigarette smoking was strongly associated with increased risk of colorectal adenomas. Overall, neither the CYP1A1 MspI genotype nor the GSTM1 genotype was related to colorectal adenomas. A significant trend for increased risk of colorectal adenomas associated with smoking was observed for each of the CYP1A1 MspI genotypes, and the increasing trends did not differ by MspI genotype. The positive association between smoking and colorectal adenomas did not vary much with GSTM1 genotypes. Among former and current smokers, adenoma risk did not differ according to the combination of CYP1A1 MspI and GSTM1 genotypes. CYP1A1 MspI and GSTM1 genotypes do not seem to modify the risk of colorectal adenomas associated with cigarette smoking.

Methylenetetrahydrofolate reductase polymorphism and risk of colorectal adenomas.

A homozygous mutation at bp 677 in the gene for the methylenetetrahydrofolate reductase (MTHFR) was previously shown to be associated with a decreased risk of colorectal cancer. We examined the relation between the MTHFR genetic polymorphism and risk of colorectal adenoma in Japanese men using 205 cases of colorectal adenomas and 220 controls of normal total colonoscopy. The homozygous mutation was not measurably associated with colorectal adenomas. The findings corroborate the lack of an association between the MTHFR genotype and colorectal adenomas, but do not deny the possibility that the genotype may be involved in the late stage of colorectal carcinogenesis.

Pigmented intraosseous odontogenic carcinoma of the maxilla: a pediatric case report and differential diagnosis.

We report a pigmented intraosseous odontogenic carcinoma of the maxilla occurring in a 6-year-old Japanese boy. Grossly, the tumor showed solid, gray-yellow, and markedly pigmented appearance. Histology showed neoplastic growths of atypical epithelial cells that occasionally contained melanin pigments. Melanocytes with dendritic processes were often found in the tumor cell clusters, and solitary or aggregated melanophages were scattered within the dense fibrovascular stroma. The tumor cells were diffusely positive for cytokeratins and epithelial membrane antigen, and focally positive for vimentin, neuron specific enolase, neurofilament protein, carcinoembryonic antigen, and amelogenin. Ultrastructural studies showed well-developed intercellular junctions, mainly desmosomes, and glycogen particles. In addition, some tumor cells contained melanosomes and/or a few neurosecretory granules. We consider that the present tumor suggests a close association of ectoderm, mesenchyma, and neuroectoderm in embryogenesis of the tooth, and can raise a diagnostic confusion with melanotic neuroectodermal tumor.

Analysis of physician ability in the measurement of pulsus paradoxus by sphygmomanometry.

CONTEXT: Measurement of pulsus paradoxus (PP) is one of several measures previously advocated in the National Heart, Lung, and Blood Institute asthma management guidelines: a pulsus of > 12 mm Hg warranted hospital admission. It is one of only a few measures that is not effort dependent and therefore important in the evaluation of patients with asthma. OBJECTIVE: Determination of physician accuracy in measuring PP. DESIGN: A model of induced PP in a trained healthy subject without respiratory disease was constructed with a fixed inspiratory resistance with measurement of inspiratory air pressure and beat-to-beat BP noninvasively. SETTING: Laboratory. PARTICIPANTS: Attending physicians from emergency medicine and critical care disciplines who served as consecutive examiners of the trained reference subject generating known PP. INTERVENTIONS: A total of 19 attending physicians were assessed for ability in measuring PP by sphygmomanometry and by palpation. The reference subject generated 4 degrees of PP sequentially, with each examiner blinded to the value of negative inspiratory pressure and PP. Examiners first assessed PP qualitatively by palpation, followed by its measurement within 2 min. MAIN OUTCOME MEASURE: Proximity of physician-measured PP (PPm) to true PP (PPt). RESULTS: At inspiratory pressures of - 10, - 15, - 20, and - 25 mm Hg, PPt was 13.7, 16.2, 19.1, and 20.7 mm Hg, respectively (F = 14.8, p < 0. 0001; analysis of variance [ANOVA]). At the same pressures, PPm was 13.1, 17.5, 17.7, and 18.0 mm Hg (p > 0.10; ANOVA). Linear regression of PPm against PPt for each examiner revealed a slope (SE) of 0.53 (0.23), and not a 1:1 relationship. CONCLUSIONS: Past and present guidelines do not account for the challenges in measuring PP, especially in tachypneic patients. Sphygmomanometric determination of PP should be augmented by new aids developed through technological innovation.

Calcium phosphate clusters.

The potential energy surfaces associated with [Ca3(PO4)2n clusters are analyzed in detail using ab initio calculations for n ranging from one to four. Considering separated clusters, energy criteria favor the so-called Posner's cluster Ca9(PO4)6, which is the core of the actual structural model of amorphous calcium phosphate. This is rationalized through the existence of a distinct CaO bonding pattern in this cluster. Considering aggregated clusters as a possible model for amorphous calcium phosphate, the aggregation of Ca3(PO4)2 clusters appears as an alternative to Posner's hypothesis.

In vitro bioactivity of starch thermoplastic/hydroxyapatite composite biomaterials: an in situ study using atomic force microscopy.

The in vitro bioactivity of a composite composed by a biodegradable starch-based polymeric matrix and hydroxyapatite fillers was investigated, in situ, as a function of immersion time in a simulated body fluid (SBF) using atomic force microscopy (AFM). The surface roughness of the composite started to increase after the initial 8h because of both the degradation of the polymer matrix and the nucleation of calcium phosphate. After 24h of immersion the surface of the composite was fully covered with calcium phosphate nuclei with diameters around 126 nm. As the immersion time increased, the nuclei increased both in number and size, and coalesced leading to the formation of a dense and uniform calcium phosphate layer on the surface of the composite only after 126 h of SBF immersion. The results of in situ AFM observation agreed with those of standard in vitro bioactivity tests in combination with scanning electron microscopy observations. Thin-film X-ray diffraction demonstrated that the ratio of apatite to the polymer matrix was higher within the surface layer (40 microm deep from the surface) than that in the bulk after the immersion for 7 days. The water-uptake capability of the polymer contributes to the nucleation and growth of the calcium phosphate layer. These results suggest the great potential of the composite for a range of temporary applications in which bone-bonding ability is a desired property.

Mechanical properties of hydroxyapatite and OH-carbonated hydroxyapatite single crystals.

Single-crystal hydroxyapatite and OH-carbonated hydroxyapatite have bending strength much higher than that of dense hydroxyapatite ceramic, indicating potential applicability to a load-bearing biomaterial. However, the effects of carbonate on the strength are less clear. The objective of the present study was to determine the bending strength and Young's modulus of these single crystals with carbonate contents from 0 to 0.62 in CO2 wt%. Three-point bending tests were performed by means of a modified ultra-microhardness tester with a span of 380 microm and a bending direction <210> of the single crystals. The crystals were broken in air, water, and air after immersion in a cell culture medium for 3 wks. The average Young's modulus of the single crystals was from 54 to 79 GPa. The average bending strength of the single crystals in air was 500+/-184, 468+/-205, 513+/-151, and 450+/-162 MPa for those with 0, 0.09, 0.37, and 0.62 wt% carbonate, respectively. No significant decrease in strength was found for hydroxyapatite single crystals both in water and after the immersion in the medium. However, the strength of OH-carbonated hydroxyapatite single crystals decreased significantly by 23 to 43% in water in proportion to the carbonate content. The strength of single crystals with 0.37 and 0.62 wt% carbonate decreased significantly, even after the immersion in the medium. Therefore, hydroxyapatite single crystals are superior to OH-carbonated hydroxyapatite single crystals as a biomaterial for a load-bearing purpose.

[New inactivating enzyme of aminoglycoside antibiotics produced by genes on R-plasmid of Serratia spp. and nosocomial infection].

Though incident due to Serratia spp. has decreased with the use of third generation cephems, S. marcescens with multiple drug resistance are still clinically occasionally isolated S. marcescens strains 218, 219 and 220 we isolated clinically, were found to possess aminoglycoside inactivating enzyme activities which had not been expected to exist in Serratia spp. These isolates inactivated aminoglycoside antibiotics except strains 218 and 219 were sensitive to isepamicin whereas strain 220 was sensitive to isepamicin and gentamicin. It was found that strains 218 and 219 possessed aminoglycoside inactivating enzyme AAC(2'), and strain 220 AAC (6'). The genes coding for these inactivating enzymes were found to be on R-plasmid and transferred between bacterial cells. Frequencies of transfer of the R-plasmid from Serratia to Escherichia coli chi-1037 were be low, but the transfer definitely occurred as frequencies of 4.3 x 10(-7) from strain 218, 5.2 x 10(-7) from strain 219, and 8.3 x 10(-7) from 220 were determined. To prevent nosocomial infections, the eradication of multi-resistant Serratia strains is strongly recommended when they are isolated even apparent symptoms of infections are not observed.

[Clinical examination of ceftibuten in acute bronchitis].

Clinical evaluation of ceftibuten (CETB, 7432-S) was performed in 20 patients with acute bronchitis. They were consisted of 10 males and 10 females aged from 20 to 80 years old. CETB was given orally in daily dose of 300 mg (18 cases) or 600 mg (2 cases) in three divided portions. The duration of administration was 3 to 14 days. Especially they were given for 7 days in 16 cases. A total of 11 strains comprising 4 strains of Staphylococcus aureus, 2 strains of beta-Streptococcus and 1 strain each of Streptococcus pneumoniae, Branhamella catarrhalis, Klebsiella oxytoca, Serratia marcescens, Acinetobacter lwoffii were identified from sputa before administration. All of the above bacteria were eradicated but, in 1 case, a strain of Streptococcus pyogenes appeared after the treatment (eradication ratio = 100%). The clinical efficacy rate was 100%: Responses were excellent in 3 cases and good in 17 cases. There was no side effect and no abnormal changes in laboratory test results. From the avobe results, it is concluded that CETB is effective, safe and useful new oral cephem on acute bronchitis.

Spin disorder and order in quasi-2D triangular Heisenberg antiferromagnets: comparative study of FeGa2S4, Fe2Ga2S5, and NiGa2S4.

Our single crystal study reveals that the single-layer S=2 triangular Heisenberg antiferromagnet FeGa2S4 forms a frozen spin-disordered state, similar to the S=1 isostructural magnet NiGa2S4. In this state, the magnetic specific heat C{M} is not only insensitive to the field, but shows a T2 dependence that scales to C{M} of NiGa2S4, suggesting the same underlying mechanism of the 2D coherent behavior. In contrast, the bilayer system Fe2Ga2S5 exhibits a 3D antiferromagnetic order.

Prevention of inflammation-mediated acquisition of metastatic properties of benign mouse fibrosarcoma cells by administration of an orally available superoxide dismutase.

Weakly tumorigenic and nonmetastatic QR-32 cells derived from a fibrosarcoma in C57BL6 mouse are converted to malignant cells once they have grown after being coimplanted with a gelatine sponge which induces inflammation. We administered a newly developed peroral superoxide dismutase (SOD), oxykine, and as control vehicle, gliadin and saline, starting 2 days before the coimplantation and continued daily throughout the experiment. In the oxykine group, tumour incidence was lower (41%) than in the gliadin or saline group (83 and 79%, respectively). The inhibitory effect of oxykine was lost when an individual component of oxykine was administered, that is, SOD alone and gliadin alone. The effect was also abolished when administered by intraperitoneal route. When perfused in situ with nitroblue tetrazolium, an indicator of superoxide formation, the tumour masses from gliadin and saline groups displayed intense formazan deposition, whereas, those from oxykine group had less deposition. Enzymatic activity of SOD was also increased in oxykine group. Arising tumour cells in gliadin and saline groups acquired metastatic phenotype, but those in oxykine group showed reduced metastatic ability. These results suggested that the orally active SOD derivative prevented tumour progression promoted by inflammation, which is thought to be through scavenging inflammatory cell-derived superoxide anion.

Clinical study of drug fever induced by parenteral administration of antibiotics.

The incidence and clinical features of drug fever induced by antibiotics were investigated. Of a total of 390 patients analyzed, 193 had malignant diseases (lung cancer in most cases) and the remaining 197 had non-malignant diseases, of which the majority comprised pulmonary infectious diseases such as pneumonia, lung abscess and chronic infections. beta-Lactams most frequently induced drug fever. Piperacillin induced drug fever in 18 of 108 (17%), cefotaxime in 11 of 72 (15%), ceftizoxime in 7 of 49 (14%) and cefoperazone in 6 of 74 patients (8%). In contrast, the incidence of drug fever caused by ampicillin and that by cefazolin were in one of 39 (3%) and in none of 44 (0%), respectively. On the other hand, antimicrobial agents other than beta-lactams only rarely induced drug fever. The higher incidence of drug fever caused by newer derivatives of beta-lactam antibiotic suggests that the side chain attached to their core moiety might be involved in the mechanism of drug fever. In patients with malignancy who were on antibiotics, respiratory infection was the most frequent cause of fever exceeding 38 degrees C. In contrast, in patients with non-malignant diseases, the use of antibiotic per se was the most frequent cause of the fever which recurred during antibiotic therapy after a previous febrile episode had subsided. The most common feature of drug fever induced by the use of an antibiotic was as follows: A low-grade fever at the time of onset is followed by a high and remittent fever. The highest diurnal body temperature rises gradually, and then the fever subsides promptly after cessation of the causative antibiotic. The fever of this type accounted for 70% of all the drug fever in this study. A transient elevation of serum level of lactic dehydrogenase was associated with drug fever in one half (25/49, 51%) of the patients. A transient and slight decrease from the normal range in counts of neutrophils and platelets were observed in 11 (23%) and in 4 (8%) of 48 patients with drug fever, respectively. These changes in laboratory findings were considered as the possible consequence of allergic processes involved in the development of drug fever and thus seem to be a helpful index for establishing the diagnosis of drug fever.

Correlation between the airway branching patterns and the heterogeneous distribution of the lesions in bleomycin-injured mouse lung: a 3-D morphometric study.

The possible roles of airway branching patterns on the pathogenesis of lung diseases, especially on the heterogeneous distribution of the lesions, were examined through three-dimensional (3-D) morphometric analysis of a mouse lung injury, induced by bleomycin. On serial sections of a mouse lung damaged by subcutaneous injection of bleomycin, we performed a computer-assisted reconstruction of the lung for visualizing the relation of airways with the distribution of the lesions, and defined the features of bronchial routes to each lesion by four parameters: LTB; the distance from the hilum, Ng; generation numbers, RD(min); irregularity of airway branching, and thetaTB; the grade of airway recurrence. Among these four parameters, only thetaTB was found to correlate with the severity of lesions (p < 0.05 by an ANOVA test), which was proved by a posthoc test (p < 0.0001). These results showing the acini supplied by recurrent branches are more prone to be damaged than those by non-recurrent branches suggest that branching patterns may underlie the heterogeneous distribution of lesions in diffuse interstitial lung diseases.

Irregularity of airway branching in a mouse bronchial tree: a 3-D morphometric study.

Limited information on the degree of irregularity of branching patterns of a bronchial tree may obscure the cause of heterogeneous distribution of the lesions in a variety of lung diseases. We reconstructed three dimensional (3-D) images from hilum to terminal bronchioles of a mouse lung, and defined the irregularity of airway branching by diameter-based morphometric analysis. The relative diameter ratios of a daughter to the parent branch (D1/D0) and those of a minor to major daughter branches (D1/D2) were calculated, and irregular dichotomies were found to be distributed in 48% of bifurcations. D1/D0 is well correlated with D1/D2, and is proved to indicate regular and irregular branching, as well as D1/D2. Irregular branches with D1/D0 smaller than 0.4 correspond to typical lateral branches, taking off from major bronchi. Our novel 3-D morphometric analysis showed the first portrayal of the 3-D structures of mouse bronchial airways, which provides a quantitative description of branching patterns leading to the correlation with distribution of lesions in the diseased lung.

In Situ Observation of Growth Process of alpha-L-Glutamic Acid with Atomic Force Microscopy.

The growth kinetics of the (111) and (001) faces of an alpha-L-glutamic acid crystal was investigated from the measurements of the growth rates, coupling with in situ surface observation using atomic force microscopy (AFM). The data of the growth rates were examined by applying the theoretical equations of the BCF and NaN models. The results indicate that the growth mechanism is not due to the screw dislocation but to the two-dimensional nucleation, i.e., the NaN model. It was confirmed by AFM observation that both the (111) and (001) faces grew with the "nucleus above nucleus" (NaN) mechanism. However, the difference of the two-dimensional nucleation behavior was observed between the faces. The growing surface of the (111) face was also observed in the presence of L-phenylaline (L-Phe) and the pinning effect by L-Phe on the growing step on the (111) face was confirmed. This result supports the mechanism of the additive effect, which was proposed previously. Copyright 2000 Academic Press.

Bending strength of synthetic OH-carbonated hydroxyapatite single crystals.

Although hydroxyapatite (HAP) is applied to medical implants because of its biocompatibility, no data on mechanical strength of HAP single crystals were yet available, partly due to the difficulty in obtaining sufficiently large single crystals. In the present study the bending strength of OH-carbonated hydroxyapatite (CHAP) single crystals containing carbonate of 0.09 CO2 wt % prepared hydrothermally was determined in three-point bending tests. The three-point bending tests were performed using a modified ultra micro-hardness tester with a span of 380 micrograms and a bending direction of <210>. The CHAP single crystals were broken in air, water, and air after immersion in alpha minimum essential medium (alpha MEM) + 10% fetal bovine serum (FBS) for 3 weeks. The average bending strength of the CHAP single crystals was 468 +/- 205, 361 +/- 199 and 501 +/- 212 MPa in air, water, and air after immersion in alpha MEM + 10% FBS, respectively. In all cases the maximum strength at each crystal thickness value decreased in inverse proportion to the thickness.