Comparison of clinical characteristics of patients with Mycobacterium avium complex disease by gender.

The clinical characteristics of male patients with pulmonary Mycobacterium avium complex disease have not been clearly defined. We aimed to clarify the clinical characteristics of male patients with pulmonary Mycobacterium avium complex disease compared with female patients.We retrospectively reviewed the medical records of patients with pulmonary Mycobacterium avium complex disease who visited the outpatient clinic of the Shinshu University Hospital between 2003 and 2016 and compared the clinical characteristics of male and female patients.A total of 234 patients with pulmonary Mycobacterium avium complex disease were identified (68 men and 166 women). Male patients were significantly older than female patients. Blood examination results showed that the lymphocyte count, total protein level and albumin level were significantly lower in men than in women. Chest imaging findings were broadly categorised into the fibrocavitary and nodular bronchiectasis types. There were no significant differences in chest imaging findings and the time from diagnosis to disease exacerbation between men and women.During the study period, the incidence of the nodular bronchiectasis type of pulmonary Mycobacterium avium complex disease in male patients increased compared with previous reports. Men had no difference in time to exacerbation compared with women.

Health-related quality of life in patients with pulmonary non-tuberculous mycobacteria infection.

BACKGROUND: The health-related quality of life (HRQoL) in patients with pulmonary non-tuberculous mycobacteria (pNTM) infection has not yet been quantified. OBJECTIVE: To evaluate the reliability and validity of the COPD Assessment Test (CAT) and St George's Respiratory Questionnaire (SGRQ) in quantifying the HRQoL of patients with pNTM. METHODS: We performed a cross-sectional study of 52 patients with pNTM. All the subjects completed the CAT, SGRQ and Short Form-36 Health Survey (SF-36) questionnaires and underwent pulmonary function testing (PFT). A test-retest was performed and Cronbach α was calculated to assess reliability. Correlations of the CAT and SGRQ with SF-36 and PFT were performed to assess validity. RESULTS: The mean age of the patients was 67 years; 96% (50/52) were female. Both individual and total CAT and SGRQ scores showed good correlation between the test on Day 1 and the repeat test on Day 5. Cronbach's α (0.77-0.92) indicated satisfactory internal consistency. All scores were moderately or strongly correlated with the SF-36 Physical Component Summary score. CONCLUSION: The SGRQ and CAT questionnaires showed statistically significant validity in assessing HRQoL in patients with pNTM.

Effects of petrissage massage on fatigue and exercise performance following intensive cycle pedalling.

OBJECTIVE: Petrissage is assumed to influence circulation as well as interstitial drainage of both superficial and deep tissues. To study its effect it was applied between consecutive bouts of supramaximal exercise performed by the lower leg muscles. METHODS: Subjects were 11 healthy female students actively engaged in sports. Exercise bouts of ergometer cycling at loads determined individually (0.075 kp x body weight (kg)) for 5 s repeated eight times at intervals of 20 s had to be performed twice on an experimental day with 35 min intermittent bed rest. Each subject was investigated on two occasions with a minimum interval of 1 week, once without (control, CO) and once with 10 min petrissage (massage, MA) of the exercising lower leg during the bed rest phase. Effects of exercise bouts on blood lactate, muscle stiffness and perceived lower limb fatigue and their recovery before and after the second exercise bout were determined. RESULTS: For the first exercise bouts total power did not differ between MA and CO. Courses of blood lactate did not differ between MA and CO. However, recovery from measured muscle stiffness (p<0.05) and perceived lower limb fatigue (p<0.05) were more pronounced and total power during the second exercise bout was enhanced (p<0.01) in MA as compared with CO subjects. CONCLUSION: Petrissage improved cycle ergometer pedalling performance independent of blood lactate but in correlation with improved recovery from muscle stiffness and perceived lower limb fatigue.

Sequence analysis of the pro-opiomelanocortin (POMC) gene in obese/diabetic Japanese.

Pro-opiomelanocortin (POMC)-derived peptides play a critical role in body weight regulation in the central nervous system. Mice deficient in POMC developed obesity. We sought mutations in the POMC gene in 50 morbidly obese (body mass index 35-60 kg/m(2)) Japanese subjects with diabetes by direct sequencing. Apart from two silent mutations (C6982T and C7285T), no other mutations were detected. Frequencies of these mutations were not significantly different between 100 obese subjects and 100 controls. Also, the frequencies did not differ in the subjects with or without diabetes. These results suggest that mutations in the POMC gene are unlikely to be a major factor of obesity or diabetes in Japanese subjects.

A rare case of a facial-nerve neurofibroma in the parotid gland.

The incidence of solitary neurofibroma of the facial nerve originating in the parotid region is extremely low. We report a case of a solitary neurofibroma in a 30-year-old male, who initially presented with a parotid mass without facial paresis or paralysis. A chain of small nodules had been palpable in the right parotid region for the previous 2-3 years. MRI and CT scans revealed several small ovoid lesions extending from the frontal margin of the parotid gland to the retromandibular region. The lesions were surgically removed. The main trunk of the facial nerve was adherent to the dorsal side of the largest nodule; however, this mass was resected atraumatically. Histopathological examination indicated neurofibroma. The incidence, presentation, diagnosis and surgical treatment of intraparotid neurofibroma are discussed and compared with those of Schwannoma.

Induction of photoreceptor-specific phenotypes in adult mammalian iris tissue.

We show that iris tissue in the adult rat eye, which is embryonically related to the neural retina, can generate cells expressing differentiated neuronal antigens. In addition, the Crx gene transfer induced the specific antigens for rod photoreceptors in the iris-derived cells, which was not seen in the adult hippocampus-derived neural stem cells. Our findings demonstrate a remarkable plasticity of adult iris tissue with potential clinical applications, as autologous iris tissue can be feasibly obtained with peripheral iridectomy.

Superantigens and autoantigens may be involved in the pathogenesis of gastric mucosa-associated lymphoid tissue lymphoma.

To clarify the origin of tumor cells and the possible role of antigens in the pathogenesis of mucosa-associated lymphoid tissue lymphoma (MALTL) of the stomach, we analyzed the DNA sequences of the immunoglobulin (Ig) variable region gene from tumor cells of 4 patients with low-grade and 2 patients with high-grade MALTL associated with Helicobacter pylori infection. There were few somatic mutations in the Ig variable region gene, but intraclonal variations were observed in 2 of the 4 low-grade MALTL cases. In the remaining 2 low-grade MALTL and 1 of the 2 high-grade MALTL cases, somatic mutations and intraclonal variations were evident. In contrast, somatic mutations in the Ig variable region gene were prominent, but intraclonal variation was absent in the other high-grade MALTL cases. The deduced amino acid sequences of the antigen-binding fragments (Fab) from 2 MALTL cases revealed homology with anti-thyroglobulin antibodies, 3 MALTL cases with lupus anti-DNA antibodies, and 1 MALTL case with a rheumatoid factor. Furthermore, the heavy-chain variable region 3 (V(H)3) family genes were used in 5 of the 6 MALTL cases and had conserved amino acid residues for binding to staphylococcal protein A (SpA), a superantigen of B cells. Considering that another superantigen, protein Fv, competes for binding to Fab with SpA and has been shown to play a major role in immune defenses against gut pathogens, SpA and possibly protein Fv may contribute to the development of MALTL. Thus, these observations suggest that most gastric MALTLs arise from memory B cells that are preliminarily activated by superantigens and autoantigens.

Cloning, sequencing, and expression of the gene encoding an intracellular beta-D-xylosidase from Streptomyces thermoviolaceus OPC-520.

The intracellular beta-xylosidase was induced when Streptomyces thermoviolaceus OPC-520 was grown at 50 degrees C in a minimal medium containing xylan or xylooligosaccharides. The 82-kDa protein with beta-xylosidase activity was partially purified and its N-terminal amino acid sequence was analyzed. The gene encoding the enzyme was cloned, sequenced, and expressed in Escherichia coli. The bxlA gene consists of a 2,100-bp open reading frame encoding 770 amino acids. The deduced amino acid sequence of the bxlA gene product had significant similarity with beta-xylosidases classified into family 3 of glycosyl hydrolases. The bxlA gene was expressed in E. coli, and the recombinant protein was purified to homogeneity. The enzyme was a monomer with a molecular mass of 82 kDa. The purified enzyme showed hydrolytic activity towards only p-nitrophenyl-beta-D-xylopyranoside among the synthetic glycosides tested. Thin-layer chromatography analysis showed that the enzyme is an exo-type enzyme that hydrolyze xylooligosaccharides, but had no activity toward xylan. High activity against pNPX occurred in the pH range 6.0-7.0 and temperature range 40-50 degrees C.

Interleukin-1 beta enhances and interferon-gamma suppresses activin A actions by reciprocally regulating activin A and follistatin secretion from bone marrow stromal fibroblasts.

Activin A is a multi-functional cytokine with a potent stimulation on erythroid cell differentiation in the bone marrow. The actions of activin A are determined by a balance of the levels of activin A and its inhibitor, follistatin (FS). However, the regulation of its actions in the bone marrow has been unclear. Here we show that bone marrow-derived stromal fibroblasts are the major source of activin A and FS in the bone marrow, and that the production of activin A is enhanced by interleukin-1beta (IL-1beta) and lipopolysaccharide (LPS), whereas interferon-gamma (IFN-gamma) inhibits the secretion of activin A by stromal fibroblasts. Concomitantly, IL-1beta as well as LPS inhibits and IFN-gamma stimulates FS secretion from stromal fibroblasts. Thus, these cytokines potently regulate activin A actions by reciprocal modulation of activin A and FS secretion from stromal fibroblasts. Because activin A exhibits anti-inflammatory effects in various tissues, up-regulation of activin A actions by IL-1beta and endotoxin in the bone marrow may play a protective role against inflammatory processes as well as anaemia. The present results also suggest that the inhibitory effect of IFN-gamma on erythropoiesis is mediated at least in part by a suppression of activin A actions in bone marrow.

The intensely positively charged perineuronal net in the adult rat brain, with special reference to its reactions to oxine, chondroitinase ABC, hyaluronidase and collagenase.

Light microscopic observations of healthy adult rat brain sections stained with anionic iron colloid indicated that 5-10% of neurons in the hippocampal subiculum and all neurons in the medial cerebellar nucleus possessed an intensely positively charged perineuronal net. This net was demonstrated to react to oxine, and therefore suggested to consist of guanidino compounds. It was further shown that the intensely positively charged perineuronal net, in accordance with the intensely negatively charged perineuronal net of proteoglycans, was digested by chondroitinase ABC, hyaluronidase, and collagenase, but not by endo-alphaN-acetylgalactosaminidase. This finding suggested that the former positively charged net might be linked to the latter negatively charged one.

Preparation of potent cytotoxic ribonucleases by cationization: enhanced cellular uptake and decreased interaction with ribonuclease inhibitor by chemical modification of carboxyl groups.

Carboxyl groups of bovine RNase A were amidated with ethylenediamine (to convert negative charges of carboxylate anions to positive ones), 2-aminoethanol (to eliminate negative charges), and taurine (to keep negative charges), respectively, by a carbodiimide reaction. Human RNase 1 was also modified with ethylenediamine. Surprisingly, the modified RNases were all cytotoxic toward 3T3-SV-40 cells despite their decreased ribonucleolytic activity. However, their enzymatic activity was not completely eliminated by the presence of excess cytosolic RNase inhibitor (RI). As for native RNase A and RNase 1 which were not cytotoxic, they were completely inactivated by RI. More interestingly, within the cytotoxic RNase derivatives, cytotoxicity correlated well with the net positive charge. RNase 1 and RNase A modified with ethylenediamine were more cytotoxic than naturally occurring cytotoxic bovine seminal RNase. An experiment using the fluorescence-labeled RNase derivatives indicated that the more cationic RNases were more efficiently adsorbed to the cells. Thus, it is suggested that the modification of carboxyl groups could change complementarity of RNase to RI and as a result endow RNase cytotoxicity and that cationization enhances the efficiency of cellular uptake of RNase so as to strengthen its cytotoxicity. The finding that an extracellular human enzyme such as RNase 1 could be effectively internalized into the cell by cationization suggests that cationization is a simple strategy for efficient delivery of a protein into cells and may open the way of the development of new therapeutics.

Hyperthermic enhancement of the apoptotic and antiproliferative activities of paclitaxel.

The antineoplastic agent paclitaxel (PTX), a microtubule-stabilizing agent, is known to arrest cell cycle progression and induce apoptosis. Mild hyperthermia (HT) also disrupts the microtubule system and triggers apoptosis. We therefore investigated whether concurrent exposure of murine breast cancer cells to 10 micromol/l PTX and 43 degrees C HT will promote improved anticancer effects. To do this, we exposed FM3A murine cancer cells to: (1) 10 micromol/l PTX for 1 h at 37 degrees C followed by exposure at 43 degrees C HT for 1 h; (2) 10 micromol/l PTX at 37 degrees C for 2 h; (3) 37 degrees C for 1 h followed by 43 degrees C HT for 1 h, and (4) untreated cells at 37 degrees C for 2 h which served as the control. Treatment No. 1 resulted in an enhanced cell cycle arrest, apoptosis and cytotoxicity. Exposure to 43 degrees C HT alone or 10 micromol/l PTX alone induced lesser apoptosis and cytotoxicity than the two treatments concurrently applied. The apoptotic cell death occurred in a time-dependent manner as follows: (1) concurrently applied 43 degrees C HT and 10 micromol/l PTX (5.6 +/- 0.5, 16.5 +/- 2 and 27.6 +/- 1%); (2) 43 degrees C HT alone (4.3 +/- 1, 6.6 +/- 0.3 and 12.7 +/- 1%) and (3) 10 micromol/l PTX alone (4.4 +/- 0.3, 8.6 +/- 1 and 12.8 +/- 1%) at 1, 6 and 24 h postexposure respectively compared to control of 2.0%. These data indicate that while both HT and PTX can individually induce apoptosis and antiproliferation in FM3A cancer cells, they may offer synergistic benefits when used concurrently.

In vivo NMR micro-imaging of kidney and liver of mouse at 9.4 T.

NMR micro-images of the kidney and liver were measured at 9.4 T in intact mouse, schistosoma Mansoni-infected mouse, and lupus nephritis in an MRL/lpr mouse. High-field NMR imaging has the advantages of sensitivity, spatial resolution, and tissue contrasts based on longitudinal and transverse relaxations, magnetic susceptibility differences and blood flow.

Oculocardiac reflex induced by zygomatic fracture; a case report.

Oculocardiac reflex has been recognized as the result of mechanical stimulation to the orbital tissue. The authors encountered a case of severe arrhythmia due to oculocardiac reflex in a patient with a zygomatic fracture. Previous health examinations suggested no abnormalities in the heart in his schooldays, and the initial diagnosis of his arrhythmia as complete A-V block due to injury (using ECG and cardiac ultrasonography). Because his arrhythmia did not improve spontaneously, he underwent cardiac pacing. After repair of the fracture, his arrhythmia completely disappeared. The pacemaker was removed on the first postoperative day. The pathogenesis of this rare case will be discussed.

[Treatment of 522 patients with sudden deafness performed oxygenation at high pressure].

INTRODUCTION: Oxygenation at high pressure (OHP) is thought to be useful, even though regional blood flow is decreased, because increasing dissolved oxygen prevents the death of nerve tissue. In this report, we retrospectively investigated the effect of OHP on sudden deafness. OBJECT AND METHOD: We reviewed 522 patients treated with OHP at Kagawa Rosai Hospital over a ten-year period (January 1989 to December 1998). We discussed some prognostic factors: comparison between cases which had been treated with OHP previously and those which had not, number of days between onset and beginning of the treatment which included OHP, age, initial averaged five-frequency hearing level, vertigo, tinnitus, complications of OHP, cases of relapse and the time of the onset, which is about season, month and week. OHP was administered at a pressure of 2.5 atmospheres for 80 minutes a day from 10 to 15 times. All patients also received a course of intravenous administration of steroid, vitamin B12, Prostaglandin E1, ATP, and low-molecular dextran. RESULTS: Overall, complete recovery occurred in 19.7% of the patients, definite improvement in 34.9% (complete recovery included), and slight improvement in 58.1% (definite improvement included). Most of the patients (78.0%) were referred by other hospitals, because our hospital was the only one in the Sikoku area which had a big equipment of OHP. All 161 patients had already been treated in other hospitals over 8 days, but they had shown little improvement after the initial therapy. Of this group, complete recovery after the second course of treatment occurred in 13.0% of the patients, definite improvement in 19.3%, and slight improvement in 39.1%. OHP was thus effective for about 40% of patients who had been unresponsive to the initial therapy. Delay in treatment usually produces poor hearing recovery. There was a significant difference between those patients treated within 14 days and those treated 15 days or more after onset. The improvement rate also decreased with age. The prognosis of patients with vertigo was worse than those without vertigo. Tinnitus had no influence on the prognosis. There were no severe complications during the course of OHP, but otitis media with effusion occurred in 90 patients, and paracentesis was performed for 53 patients. CONCLUSION: The treatment of sudden deafness with OHP has been discussed in this report. Important prognostic factors were time between onset and beginning of the treatment which included OHP, age, vertigo, and the initial averaged five-frequency hearing level. We conclude that OHP should be performed within 14 days from onset, and that OHP was able to achieve hearing improvement in many cases unresponsive to the initial therapy if it was performed very early.