Biosynthesis of biotin-vitamers by family Enterobacteriaceae

The biosynthesis of biotin-vitamers from various carbon sources by the members of the Enterobacteriaceae as one of the groups of intestinal bacteria was investigated. The biotin-vitamers synthesized in each case included one or more of dethiobiotin (main product), 7-keto-8-aminopelargonic acid, and biotin. True biotin was shown to be synthesized under aerobic conditions but not under anaerobic conditions by each of several strains belonging to one of the genera, Erwinia, Escherichia, Proteus, and Serratia, and using culture media containing one of galactose, peptone, Polypepton, or casamino acid. In addition, a biotin precursor, pimelic acid, was also synthesized by several bacteria utilizing carbon sources such as maltose, mannose, galactose, peptone, or casamino acid.     

Triad of thymoma,myasthenia gravis and pure red cell aplasia combined with Sjögren’s syndrome

A 36-year-old woman complained of cough and high fever. Computed tomographic scans demonstrated a mediastinal mass. A couple of months later, she developed dryness in her eyes and mouth. Biopsy of the lip confirmed the diagnosis of Sjögren’s syndrome. She underwent thymo-thymomectomy. Pathological findings of the mass revealed thymoma. At two months after surgery, she developed ptosis and dysphagia that were compatible with myasthenia gravis. The clinical symptoms were adequately controlled with prednisolone. At eleven months after surgery, she presented with severe anemia, which led to the diagnosis of pure red cell aplasia. The following treatment with cyclosporin caused hemoglobin concentration to rise. However, she continues to suffer from dryness of her eyes and mouth. The case is the first to be reported with Sjögren’s syndrome and the triad of thymoma, myasthenia gravis and pure red cell aplasia, and is compared with previously reported cases of the three conditions.     

Independent association of antibodies against human papillomavirus type 16 and E7 proteins with cervical cancer

The E4 open reading frame (ORF) of human papillomaviruses (HPVs) is transcribed in abundant mRNAs encoding an fusion gene during the productive infection, and the HPV 16 E7 ORF encodes an oncoprotein detectable in the cell lines derived from cervical carcinoma. We examined 421 human sera, which included 108 samples from the patients with cervical carcinoma, for the presence of IgG antibodies against the HPV 16 E4 and E7 proteins by enzyme-linked immunosorbent assay. Bacterially expressed fusion protein lac- and nonfusion protein E7 were purified and used as antigens. All of the 22 serum samples positive for anti-E7 antibody and the 11 out of 15 samples positive for anti- antibody were from the patients with cervical carcinoma, but only one sample was found to contain both anti- and anti-E7 antibodies. These findings show specific and independent association of these antibodies with cervical carcinoma.     

The effect of the neurokinin antagonist FK-224 on the cough response to inhaled capsaicin in a new model of guinea-pig eosinophilic bronchitis induced by intranasal polymyxin B

Eosinophilic bronchitis without asthma can cause a persistent non-productive cough which is resistant to bronchodilator therapy. To understand the mechanism of the cough in this disorder, an animal model of eosinophilic bronchitis was developed. Guinea-pigs were treated with transnasal administration of polymyxin B or saline twice a week for 3 weeks. The number of eosinophils in bronchoalveolar lavage fluid increased in polymyxin B-treated animals when compared with those treated with saline. In addition, histological examination showed that the number of eosinophils infiltrated into the tracheal epithelium increased; injury to the tracheal epithelium was greater in polymyxin B-treated animals. The numbers of coughs induced by saline and each concentration of capsaicin (10^–18, 10^–16, 10^–14M) were greater in the polymyxin B-treated animals. FK-224 (a neurokinin receptor antagonist) decreased the heightened cough reflex in this animal model of eosinophilic bronchitis. These findings suggest that neuropeptides, and particularly neurokinins, are involved in the heightened cough receptor sensitivity in eosinophilic bronchitis without asthma. This has implications for better understanding of this disorder and its treatment.     

Intense and prolonged Tl-201 accumulation in a slow growing bronchioloalveolar carcinoma

Thallium-201 SPECT was performed to evaluate a pulmonary lesion in a 73-year-old male which had been considered to be an inflammatory lesion for two years. The lesion has slowly increased in size on x-CT. Tl-201 was intensely taken up and retained in the lesion, suggesting a malignant lesion. Histological examination revealed that the lesion was bronchioloalveolar carcinoma. This case suggested that Tl-201 uptake of pulmonary carcinoma would not be necessarily related to cell growth rate.     

Histological evaluation of medial patellofemoral ligament reconstructed using the Leeds-Keio ligament prosthesis

In a total of 15 knees from 15 patients undergoing medial patellofemoral ligament reconstruction using an artificial substitute and a medial retinaculum slip coverage for recurrent patellar dislocation, the reconstructed ligaments were histologically evaluated using hematoxilin-eosin and elastic van Gieson stains. The artificial substitute was a mesh-type Leeds-Keio ligament. The mean age of the patients at the time of surgery was 20 years (range; 13-38 years). The mean interval from initial reconstruction to gathering was 53 months (range; 11-109 months). In the tissue over the artificial ligament, longitudinally aligned collagen fiber bundles with spindle-shaped nuclei were formed in all specimens except one specimen of 11 months postsurgery, but it seemed to be mature ligament only in specimens more than 60 months postsurgery. The tissue inside the artificial ligament was immature as a whole in all specimens, although 13 out of the 15 specimens had regularly aligned collagen fiber bundles slightly or in some portions.     

Activities of a soluble extract from lymphoid cells of MRL mice. Effect on B cell differentiation in vitro

Soluble extract (sEx) was prepared from lymphoid cells of MRL/Mp-lpr/lpr(MRL/l) mice with early lupus nephritis and also of MRL/Mp-+/+ (MRL/n) mice. sEx from lymph node and spleen T cells of MRL/l mice had an activity for B cells to differentiate into immunoglobulin-producing cells but that of MRL/n mice did not show such an activity. sEx of MRL/l mice also enhanced the in vitro response of B cells to a suboptimal dose of lipopolysaccharide. Implication of these phenomena in the development of lupus nephritis is discussed.     

Altered EphA5 mRNA expression in rat brain with a single methamphetamine treatment

Methamphetamine is a potent and indirect dopaminergic agonist which can cause chronic brain dysfunctions including drug abuse, drug dependence and drug-induced psychosis. Methamphetamine is known to trigger molecular mechanisms involved in associative learning and memory, and thereby alter patterns of synaptic connectivity. The persistent risk of relapse in methamphetamine abuse, dependence and psychosis may be caused by such alterations in synaptic connectivity. EphA5 receptors constitute large families of tyrosine kinase receptor and are expressed almost exclusively in the nervous system, especially in the limbic structures. Recent studies suggest EphA5 to be important in the topographic projection, development, and plasticity of limbic structures, and to be involved in dopaminergic neurotransmission. We used in situ hybridization to examine whether methamphetamine alters EphA5 mRNA expression in the brains of adult male Wister rats. EphA5 mRNA was widely distributed in the medial frontal cortex, cingulate cortex, piriform cortex, hippocampus, habenular nucleus and amygdala. Compared to baseline expression at 0 h, EphA5 mRNA was significantly decreased (by 20%) in the medial frontal cortex at 24 h, significantly increased (by 30%) in the amygdala at 9 and 24 h, significantly but transiently decreased (by 30%) in the habenular nucleus at 1 h after a single injection of methamphetamine. Methamphetamine did not change EphA5 mRNA expression in the cingulate cortex, piriform cortex or hippocampus. Our results that methamphetamine altered EphA5 mRNA expression in rat brain suggest methamphetamine could affect patterns of synaptic connectivity, which might be responsible for methamphetamine-induced chronic brain dysfunctions.     

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.