Utility of 5-aminolaevulinic acid fluorescence-guided endoscopic biopsy for malignant mesothelioma in a cat and dog.

Malignant mesothelioma (MM) is uncommon in cats and dogs and can be challenging to diagnose. Adequate tissue sampling is required for superior diagnostic accuracy. Protoporphyrin IX, a metabolite of 5-aminolaevulinic acid (5-ALA), is a photosensitiser for photodynamic diagnosis (PDD). To the best of our knowledge, no study has reported the use of 5-ALA-PDD to detect MM in veterinary medicine. The present study describes the use of 5-ALA-PDD for MM diagnosis in a cat and dog, as well as the effectiveness of intracavitary chemotherapy. We evaluated the use of PDD with 5-ALA hydrochloride (5-ALA-PDD) in two cases of MM. A 12-year-old cat presented with a 1-month history of respiratory distress, and a 9-year-old dog presented with a 3-month history of mild abdominal distention. We endoscopically biopsied lesions in both the cases using 5-ALA-PDD. Histopathological examination revealed mesothelioma, and immunohistochemical staining was positive for calretinin. Both patients were treated with carboplatin. The cat died of respiratory failure. Although, the dog's condition improved 21 days after the first chemotherapeutic drug administration, the dog died on day 684 owing to cardiac-related issues. 5-ALA-PDD is thus, safe and feasible for the diagnosis of MM in veterinary medicine.

Photon number resolving SiPM detector with 1 GHz count rate.

We demonstrate 1 GHz count rate photon detection with photon number resolution by using a multi-pixel photon counter (MPPC) and performing baseline correction. A bare MPPC chip mounted on a high-frequency circuit board is employed to increase response speed. The photon number resolving capability is investigated at high repetition rates. This capability remains at a repetition rate of 1 GHz and at rates as high as an average of 2.6 photons detected per optical pulse. The photon detection efficiencies are 16% at λ = 450 nm and 4.5% at λ = 775 nm with a dark count rate of 270 kcps and an afterpulse probability of 0.007.

Is response rate increment obtained by molecular targeted agents related to survival benefit in the phase III trials of advanced cancer?

BACKGROUND: It remains unclear whether response rate (RR) is related to survival benefit in phase III trials of advanced cancer treated with molecular targeted agents (MTA) in combination with standard therapies. MATERIALS AND METHODS: We carried out a systematic search of PubMed for randomized phase III trials of four solid tumors examining the efficacy of MTA when added to a standard therapy. We examined whether there were any associations between RR increment obtained by the addition of targeted agents (DeltaRR) and survival benefit in phase III trials. RESULTS: We identified 26 phase III trials of MTA with a total of 21 156 patients and 29 experimental arms of MTA. Studies which showed significant survival benefit had higher DeltaRR compared with those which did not show significant benefit. In the receiver operating characteristic curve analysis, using a 7% gain as threshold value for DeltaRR allowed assessment of survival benefit with high sensitivity and specificity. There were also significant relationships between DeltaRR and hazard ratios for overall survival and progression-free survival in the linear regression analysis. CONCLUSION: RR increment obtained by the addition of MTA to a standard therapy may be useful to predict survival benefit in clinical phase III trials of advanced cancer.

Multipixel silicon avalanche photodiode with ultralow dark count rate at liquid nitrogen temperature.

Multipixel silicon avalanche photodiodes (Si APDs) are novel photodetectors used as silicon photomultipliers (SiPMs), or multipixel photon counter (MPPC), because they have fast response, photon-number resolution, and a high count rate; one drawback, however, is the high dark count rate. We developed a system for cooling an MPPC to liquid nitrogen temperature and thus reduce the dark count rate. Our system achieved dark count rates of <0.2 cps. Here we present the afterpulse probability, counting capability, timing jitter, and photon-number resolution of our system at 78.5 K and 295 K.

Antibody mimicking the action of RAS proteins on yeast adenylyl cyclase: implication for RAS-effector interaction.

Polyclonal antisera were raised against various subregions of Saccharomyces cerevisiae adenylyl cyclase in order to examine the molecular mechanism of interaction between adenylyl cyclase and RAS proteins. One of the antisera was found to activate adenylyl cyclase to an extent comparable to that activated by saturating amounts of yeast RAS2 protein produced in Escherichia coli. The stimulatory effect of this antiserum was shown to be additive with RAS2 protein when both antisera and RAS2 protein were present at low concentrations. At saturating amounts of RAS2 protein, the antisera did not exhibit additional stimulatory effects, suggesting that the actions of RAS2 protein and the antisera are complementary with each other. The antigenic determinant for the antibody involved in the activation was mapped to a 14-amino-acid segment, 1452-NSVDNGADVANLSY-1465, located between the leucine-rich repeats and the catalytic domain of adenylyl cyclase. Certain missense mutations affecting this 14-amino acid segment significantly reduced the response of adenylyl cyclase to both activating antibody and RAS proteins. These results suggest that this segment of adenylyl cyclase is intimately involved in the mechanism by which RAS proteins activate this downstream effector.

Clinical outcomes of orbital irradiation combined with or without systemic high-dose or pulsed corticosteroids for Graves' ophthalmopathy.

PURPOSE: To evaluate the outcomes of orbital irradiation with or without high-dose or pulsed corticosteroids in patients with Graves' ophthalmopathy (GO). METHODS AND MATERIALS: One hundred and twenty-one patients with moderate to severe GO who received orbital irradiation from 1987 to 1997 were retrospectively analyzed. A total dose of 20 Gy in 10 fractions was delivered to the bilateral retrobulbar volume. Eighty-six patients were treated in combination with high-dose or pulsed corticosteroids and irradiation. Univariate and multivariate analyses were performed to assess the prognostic variables. RESULTS: The median follow-up period was 26 months. The overall clinical response was evaluated as excellent in 17 patients (14%), good in 65 (54%), fair in 31 (25%), no response in 7 (6%), and worse in 1 (1%). The best responses were noted for soft-tissue signs, extraocular muscle involvement, and sight loss, while a limited response was noted for proptosis. Multivariate analysis revealed that the use of high-dose corticosteroid or pulsed corticosteroids, female gender, and a shorter duration of ophthalmopathy before radiotherapy were significantly correlated with favorable outcomes. No long-term complications related to radiotherapy were observed. CONCLUSION: Orbital irradiation combined with high-dose or pulsed corticosteroids is an effective treatment for moderate to severe GO, especially in cases with major manifestations of soft-tissue signs, extraocular muscle impairment, or sight loss.

Dosimetric predictors of radiation esophagitis in patients treated for non-small-cell lung cancer with carboplatin/paclitaxel/radiotherapy.

PURPOSE: To establish dosimetric predictors of radiation esophagitis (RE) in patients treated with a combination of carboplatin, paclitaxel, and radiotherapy. METHODS AND MATERIALS: Three-dimensional radiotherapy plans of 26 patients with non-small-cell lung cancer who received 50-60 Gy of radiotherapy concurrently with weekly administration of carboplatin (AUC 2) and paclitaxel (40-45 mg/m(2)) were reviewed in conjunction with RE. The factors analyzed included the following: percentages of organ volumes receiving >40 Gy (V40), >45 Gy (V45), >50 Gy (V50), and >55 Gy (V55); the length of esophagus (total circumference) treated with >40 Gy (LETT40), >45 Gy (LETT45), >50 Gy (LETT50), and >55 Gy (LETT55); the maximum dose in the esophagus (Dmax); and the mean dose in the esophagus (Dmean). Data were obtained on the basis of superposition algorithm. RESULTS: All factors except Dmax showed statistical correlation with RE. Good correlations were shown between RE and LETT45 (rho = 0.714) and V45 (rho = 0.686). CONCLUSIONS: LETT45 and V45 appear to be useful dosimetric predictors of RE. It is also suggested that Dmax does not predict RE.

Endoscopic findings of radiation esophagitis in concurrent chemoradiotherapy for intrathoracic malignancies.

BACKGROUND AND PURPOSE: The incidence and extent of radiation esophagitis were assessed endoscopically in patients treated with concurrent chemoradiotherapy. PATIENTS AND METHODS: Eighty-two patients who received thoracic radiotherapy for lung, thymic, or esophageal cancer were investigated endoscopically from July 1991 to the end of 1997. Among them, 23 esophageal cancer patients were treated with radiation alone, and the others were treated with concurrent chemoradiotherapy. Esophageal endoscopy was performed during or just after radiotherapy. The presence of radiation esophagitis was assessed and assigned an endoscopic score (i.e. grade 0 for normal, 1 for erythema, 2 for erosion or sloughing, 3 for ulcer, hemorrhage, or stricture). The symptomatic grade was assessed using the RTOG (Radiation Therapy Oncology Group) acute radiation morbidity score. RESULTS: A correlation was seen between endoscopic and RTOG scores. However, even some patients with RTOG grade 0 to 1 had endoscopic grade 3 esophagitis. Endoscopic grade 3 was observed in 16 (27.1%) patients in the concurrent chemoradiotherapy group, whereas it did not occur in any patient in the radiation alone group (P=0.004). CONCLUSIONS: Our results suggest that (1) RTOG score correlates closely to esophageal mucosal damage, and (2) more severe esophagitis occurs in those undergoing concurrent chemoradiotherapy than those undergoing radiotherapy alone [corrected].

Glucose-forming amylase in human urine.

This paper describes the isolation and study of glucose-forming amylase existing in human urine as a normal component. After removing alpha-amylase [EC 3.2.1.1] by adsorption onto raw starch, urine was treated with DEAE-cellulose and Bio Gel P-150, and three fractionated proteins (F-1, F-2, and F-3), isolated in a homogeneous state by gel filtration, were shown to display glucose-formine amylase activity. They all hydrolyzed starch and glycogen, releasing glucose as the sole product, and also hydrolyzed maltose. However, their molecular weights, as estimated by gel filtration, isoelectric points, stabilities, and several enzymatic properties were different. The implications of the results are discussed.

Isozymes of alpha-amylase in human urine.

Some physicochemical properties of crystalline alpha-amylase [EC 3.2.1.1] isolated from normal human urine were investigated. A crystalline preparation of the enzyme was homogeneous on velocity sedimentation, gel filtration, and sodium dodecyl sulfate disc electrophoresis, and its molecular weight was estimated to be 4.5 X 10-4. However, electrophoretic analyses revealed that the crystalline alpha-amylase consisted of at least five isozymes. The implications of the experimental results are discussed.

Phosphocholine-bonded galactosylceramides having a tri-unsaturated long-chain base from the clam worm, Marphysa sanguinea.

Seven glycosphingolipids were obtained in the pure state from the clam worm, Marphysa sanguinea, by preparative HPLC with a reversed-phase column in a recycling mode. Their structures were elucidated based on detailed analyses of 1H- and 13C-NMR spectra of the intact compounds. The position and the geometry of double bonds in the long-chain base (LCB) were determined by the two-dimensional NMR (COSY, NOESY, and HMBC) analyses. All compounds are phosphocholine-bonded monogalactosylceramides and two of them have tri-unsaturated long-chain bases.

Morphological characteristics of a transplantable histiocytic sarcoma (HS-J) in F344 rats and appearance of renal tubular hyaline droplets in HS-J-bearing rats.

A transplantable tumour (HS-J) was established from a spontaneous histiocytic sarcoma found in a 24-month-old male F344 rat. Serial transplantations (seven generations) were made in syngeneic male and female rats by means of intraperitoneal or subcutaneous implants, with a 100% take rate. Rats given HS-J implants developed large nodules locally, with metastasis to distant organs. HS-J tumours consisted mainly of round to oval cells with abundant cytoplasm, arranged in a compact sheet. Enzyme- and immuno-histochemical examination showed that neoplastic cells reacted with ED1 (rat monocyte/macrophage-specific antibody), lysozyme, alpha 1-antitrypsin and lysosomal enzymes (acid phosphatase and non-specific esterase), indicating derivation from cells of the monocyte/macrophage lineage. The majority of neoplastic cells were negative for ED2 (rat tissue macrophage-specific antibody). Abnormal accumulations of hyaline droplets in the proximal renal tubular epithelial cells were seen in HS-J-bearing rats. The droplets were faintly immunopositive for lysozyme, but negative for alpha-2u globulin and albumin. It was considered that excessive production of the protein by tumour cells might lead to subsequent overload in renal tubules. HS-J may prove beneficial for studying the biological behaviour of monocyte/macrophage-derived tumours in the rat.

Macrophage populations and apoptotic cells in the liver before spontaneous hepatitis in Long-Evans Cinnamon (LEC) rats.

The inbred mutant strains of Long-Evans Cinnamon (LEC) rats spontaneously develops acute hepatitis as a result of abnormal copper accumulation, followed by chronic hepatitis, cholangiofibrosis and hepatocellular carcinoma. To shed some light on the role of macrophages in the liver failure, immunohistochemical methods were used to investigate the kinetics of macrophage populations in the liver of male LEC rats, in relation to the appearance of myofibroblastic cells and hepatocyte apoptosis. Rats examined at 24 weeks of age and moribund rats killed at 22-25 weeks of age had increased serum concentrations of aspartate aminotransferase and alanine aminotransferase, with jaundice and histological changes indicative of hepatic failure, whereas rats examined at 8, 12, 16 or 20 weeks old showed no such abnormal findings. Immunolabelling with ED1 (a monoclonal antibody recognizing rat macrophages) and ED2 (a monoclonal antibody specific for rat resident macrophages) revealed that numbers of blood monocyte-derived macrophages and Kupffer cells began to increase markedly at 16 weeks of age (before the onset of hepatitis). However, alpha-smooth muscle actin (SMA)-positive myofibroblastic cells (modulated perisinusoidal cells) and hepatocyte apoptosis, demonstrable by the TUNEL method, were rarely seen at 8, 12, 16, 20 or 24 weeks. There was no close relationship between macrophage expansion and the appearance of myofibroblastic cells or hepatocyte apoptosis. In moribund rats, only a few SMA-positive cells were seen in the periportal zones; hepatocytes undergoing apoptosis increased in number, and macrophages engulfing apoptotic bodies were observed occasionally, suggesting that apoptosis was related to hepatic failure as an early event. In addition, immunohistochemical examination demonstrated abnormal deposits of laminin along the sinusoids from 20 weeks, as an initial extracellular matrix protein in LEC rat livers.

Influence of progesterone and oestrogen on growth and morphology of a transplantable rat uterine smooth muscle tumour (SMT-Y).

Tumours of uterine smooth muscle are poorly understood neoplasms in which the effects of steroid sex hormones are complex. The influence of progesterone and oestrogen on a transplantable rat uterine smooth muscle tumour line (SMT-Y) was investigated. Female F344 rats given subcutaneous transplants of tumour fragments developed tumours, 1.5-2 cm in diameter, and were then treated with progesterone (10 mg/rat) or 17 beta-oestradiol (50 mg/rat). Tumours in treated groups were compared with those in untreated controls. During a 9-week observation period after treatment, progesterone promoted tumour growth from 4 weeks, with increased numbers of proliferating cells. In contrast, oestradiol inhibited tumour growth from 6 weeks; the degraded tumours, consisting mainly of vacuolated neoplastic cells, had decreased numbers of proliferating cells and increased numbers of apoptotic cells, demonstrable by in-situ terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick labelling. Immunohistochemically, tumours in control and progesterone groups were labelled positively for alpha-smooth muscle actin (SMA) and desmin but not for vimentin, whereas the degraded tumours in the oestradiol group had reduced reactivity for SMA and desmin but an increased reactivity for vimentin. These results indicate that progesterone may act as a promoter for uterine smooth muscle tumour growth by stimulating mitotic activity, whereas oestrogen may have suppressive effects on tumour growth, accompanied by morphological changes.

Expression of pulmonary mRNA encoding ICAM-1, VCAM-1, and P-selectin following thoracic irradiation in mice.

PURPOSE: Recent studies have revealed that ionizing radiation induces the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin in vitro. The purpose of this study was to investigate the expression of these adhesion molecules in mouse lung following whole thoracic irradiation. MATERIALS AND METHODS: C57BL/6J mice were irradiated with a single dose of 12 Gy to the thoraces and sacrificed at 4, 12, 24, and 48 hours and 1, 2, 4, and 8 weeks after irradiation. Expression of total lung mRNA for ICAM-1, VCAM-1, and P-selectin was quantified by the Northern blot method and normalized to beta-actin. RESULTS: There were increases in mRNA for ICAM-1 of 42% at 4 hours (p < 0.05), 76% at 24 hours (p < 0.01), and 51% at 48 hours (p < 0.05) compared with the controls. These returned to the control level at 1 week. The expression of VCAM-1 mRNA was also increased by 49% (p < 0.01) at 12 hours and was still increased by 25% at 1 week. P-selectin mRNA was transiently increased by 59% at 12 hours. CONCLUSIONS: These early inductions of mRNA for ICAM-1, VCAM-1, and P-selectin in mouse lung following thoracic irradiation were transient but significant, and are one of the most immediate changes reported in vivo.

[Serological cross-reaction among Bartonella henselae, Chlamydia pneumoniae and Coxiella burnetii by indirect fluorescence antibody method].

We studied the serological cross-reactions among Bartonella henselae, Chlamydia pneumoniae and Coxiella burnetii by indirect fluorescence antibody (IFA) method, using sera from 8 patients with cat scratch disease (CSD), 13 patients with C. pneumoniae infection and 12 patients with acute Q fever. B. henselae IgG antibody was negative in 13 patients with C. pneumoniae infection, and was positive in 3 (titers being 1:64) of 12 patients with Q fever, whereas B. henselae IgM antibody was negative in all the patients with C. pneumoniae infection or Q fever. C. burnetii IgG antibody was removed by absorption of these 3 sera with C. burnetii antigens, whereas B. henselae IgG antibody did not change. C. pneumoniae IgG antibody was positive in 3 (titers being 1:125 in two, 1:32 in one) of 8 patients with CSD. Both C. pneumoniae and B. henselae IgG antibody titers were significantly reduced by absorption of these 3 sera with B. henselae antigens. C. burnetii IgG or IgM antibodies were negative in all patients with CSD. In conclusion, no serological cross-reaction between B. henselae and C. burnetii was observed. On the other hand. B. henselae IgG antibody cross-reacted to C. pneumoniae antigens, whereas C. pneumoniae IgG antibody did not cross-react to B. henselae antigens. Our findings suggest that determination of B. henselae IgG or IgM antibodies were not influenced by C. pneumoniae and C. burnetii antigens.

A longitudinal study of the growth and development of the dental arch width from childhood to adolescence in Japanese.

The purpose of this study was to evaluate the longitudinal changes in arch width from childhood to adolescence. The subjects were 28 persons (13 males and 15 females) with untreated normal occlusion. Dental casts were taken at bimonthly intervals from childhood to adolescence. These materials were measured; the changes in the dental arch were compared on the basis of the status of the tooth emergence of certain permanent teeth and also on the chronological age from 3 years to 20 years of age. In the maxilla and mandibula, the width between the deciduous canines, the width between the first deciduous molars, and the width between the second deciduous molars were nearly stable or slightly increased until 6 years of age. After that, all of the deciduous tooth widths gradually increased, especially in the width between the deciduous canine at the emergence of the permanent incisors. The width between the canines decreased until 13 years of age in the maxilla and until 15 years of age in the mandibula. After that, the width between the canines were nearly stable. Until 1 year after emergence, the width between the canines decreased, in particular during the transition to the canines, based on dental age observation. The maxillary first premolar width decreased until 6 months after emergence, based on dental age observation. Thereafter, the width between the maxillary first premolars showed no clear change. The width between the mandibular first premolars, the width between the maxillary second premolars, and the width between the mandibular second premolars increased until about 2-3 years after emergence, but they showed no clear changes thereafter. The width between the maxillary first molars gradually increased until 15 years of age; there was no clear change thereafter. The width between the mandibular first molars was nearly stable throughout the observation period. The width between the maxillary second molars decreased until 2 years after emergence; no clear change was observed thereafter. The width between the mandibular second molars was unstable until after about 2-3 years after emergence and then became nearly stable.

The horizontally impacted maxillary canine situated in a labial position.

Surgical management of unerupted teeth depends upon a thorough understanding of anatomic, physiologic and pathologic factors. Attention has been given to problems of eruption in the maxillary anterior region. It is a region where a variety of anomalies occur. Since the maxillary anterior region influences appearance so greatly, early detection of difficulties and careful planning and treatment can be extremely beneficial to patients. The purpose of this case report is to present a case of maxillary permanent canine impaction in a horizontal displacement that developed after loss of the deciduous canine to chronic apical periodontitis, and incomplete root resorption of the deciduous canine.