Genetic aspects of immunoglobulins and cyclophilin A in milk as potential indicators of mastitis resistance in Holstein cows.

Mastitis is one of the most frequent and costly diseases affecting dairy cattle. Natural antibodies (immunoglobulins) and cyclophilin A (CyPA), the most abundant member of the family of peptidyl prolyl cis/trans isomerases, in milk may serve as indicators of mastitis resistance in dairy cattle. However, genetic information for CyPA is not available, and knowledge on the genetic and nongenetic relationships between these immune-related traits and somatic cell score (SCS) and milk yield in dairy cattle is sparse. Therefore, we aimed to comprehensively evaluate whether immune-related traits consisting of 5 Ig classes (IgG, IgG1, IgG2, IgA, and IgM) and CyPA in the test-day milk of Holstein cows can be used as genetic indicators of mastitis resistance by evaluating the genetic and nongenetic relationships with SCS in milk. The nongenetic factors affecting immune-related traits and the effects of these traits on SCS were evaluated. Furthermore, the genetic parameters of immune-related traits according to health status and genetic relationships under different SCS environments were estimated. All immune-related traits were significantly associated with SCS and directly proportional. Additionally, evaluation using a classification tree revealed that IgA, IgG2, and IgG were associated with SCS levels. Genetic factor analyses indicated that heritability estimates were low for CyPA (0.08) but moderate for IgG (0.37), IgA (0.44), and IgM (0.44), with positive genetic correlations among Ig (0.25-0.96). We also evaluated the differences in milk yield and SCS of cows between the low and high groups according to their sires' estimated breeding value for immune-related traits. In the high group, IgA had a significantly lower SCS in milk at 7 to 30 d compared with that in the low group. Furthermore, the Ig in milk had high positive genetic correlations between healthy and infected conditions (0.82-0.99), suggesting that Ig in milk under healthy conditions could interact with those under infected conditions, owing to the genetic ability based on the level of Ig in milk. Thus, Ig in milk are potential indicators for the genetic selection of mastitis resistance. However, because only the relationship between immune-related traits and SCS was investigated in this study, further study on the relationship between clinical mastitis and Ig in milk is needed before Ig can be used as an indicator of mastitis resistance.

Discovery of a novel acaricide, acynonapyr.

Acynonapyr, discovered by Nippon Soda Co., Ltd., is a novel acaricide with N-pyridyloxy azabicycle as a unique core structure. Acynonapyr exhibits high activity against the spider mite species in the genera Tetranychus and Panonychus, with good efficacy at all life stages. Early in this research, cyclic amines substituted with (hetero)aryl(oxy) moieties were designed as target molecules and diversely synthesized, and 4-[4-(trifluoromethyl)phenoxy]-1-[5-(trifluoromethyl)-2-pyridyl]piperidine was found to show weak acaricidal activity. The structural optimization of this acaricidal active piperidine as the first lead compound led to the discovery of acynonapyr. In this report, our research process that led to the discovery of acynonapyr is described.

Comprehensive Assessment of the Universal Healthcare System in Dentistry Japan: A Retrospective Observational Study.

Japan's universal healthcare insurance is facing economic challenges due to the advanced aging society, however, objective data of dental expenditure has never been introduced. This study aimed to identify the associated factors with dental expenditures using government-provided digitized insurance claims data and calculated the spending in the context of dental cost per person (DCPP). Seven associated factors analyzed were age, demographic, geographic, socioeconomic, regional wealth, the impact of the 8020-national campaign implementation (keep 20 teeth at age 80), and the effect of the home-visit dentistry for the elders. The average DCPP was high in older populations (75+) in all prefectures. The prefectures with the highest and lowest DCPP were significant compared to other states and retained their respective places in the cost hierarchy over the four years. The prefectures with more citizens participating in government assistance programs (GAP) had greater DCPPs. Dental costs were significantly related to geographic regions, age, per capita income, government assistance program prevalence, office complete denture frequency, and home visit care per patient. With a growing aging population, dental care costs will continue to increase, burdening its fiscal future. Associated factors identified should be considered to control the contentious increase of healthcare cost.

Prevention of mastitis in multiparous dairy cows with a previous history of mastitis by oral feeding with probiotic Bacillus subtilis.

Mastitis is a very common inflammatory disease of the mammary gland of dairy cows, resulting in a reduction of milk production and quality. Probiotics may serve as an alternative to antibiotics to prevent mastitis, and the use of probiotics in this way may lessen the risk of antibiotic resistant bacteria developing. We investigated the effect of oral feeding of probiotic Bacillus subtilis (BS) C-3102 strain on the onset of mastitis in dairy cows with a previous history of mastitis. BS feeding significantly decreased the incidence of mastitis, the average number of medication days and the average number of days when milk was discarded, and maintained the mean SCC in milk at a level substantially lower than the control group. BS feeding was associated with lower levels of cortisol and TBARS and increased the proportion of CD4+ T cells and CD11c+ CD172ahigh dendritic cells in the blood by flow cytometry analysis. Parturition increased the migrating frequency of granulocytes toward a milk chemoattractant cyclophilin A in the control cows, however, this was reduced by BS feeding, possibly indicating a decreased sensitivity of peripheral granulocytes to cyclophilin A. These results reveal that B. subtilis C-3102 has potential as a probiotic and has preventative capacity against mastitis in dairy cows.

Study of the Structure-Activity Relationship of an Anti-Dormant Mycobacterial Substance 3-(Phenethylamino)Demethyl(oxy)aaptamine to Create a Probe Molecule for Detecting Its Target Protein.

The current tuberculosis treatment regimen is long and complex, and its failure leads to relapse and emergence of drug resistance. One of the major reasons underlying the extended chemotherapeutic regimen is the ability of Mycobacterium tuberculosis to attain a dormant state. Therefore, the identification of new lead compounds with chemical structures different from those of conventional anti-tuberculosis drugs is essential. The compound 3-(phenethylamino)demethyl(oxy)aaptamine (PDOA, 1), isolated from marine sponge of Aaptos sp., is known as an anti-dormant mycobacterial substance, and has been reported to be effective against the drug resistant strains of M. tuberculosis. However, its target protein still remains unclear. This study aims to clarify the structure-activity relationship of 1 using 15 synthetic analogues, in order to prepare a probe molecule for detecting the target protein of 1. We succeeded in creating the compound 15 with a photoaffinity group that retained antimicrobial activity, which proved to be a suitable probe molecule for identifying the target protein of 1.

Jailed double-microcatheter technique following horizontal stenting for coil embolization of intracranial wide-necked bifurcation aneurysms: A technical report of two cases.

The horizontal stenting technique facilitates endovascular treatment of wide-necked bifurcation intracranial aneurysms. Previous literature shows, however, that subsequent coil embolization at initial treatment results in incomplete obliteration in many cases. The authors present two consecutive cases of wide-necked large bifurcation aneurysms to describe an additional coil embolization technique following horizontal stenting. The patients were a 53-year-old female with an unruptured internal carotid artery terminus aneurysm and a 57-year-old female with a recurrent basilar artery tip aneurysm. Both patients underwent endovascular treatment with horizontal stenting followed by coil embolization with jailed double-microcatheters. Immediate complete obliteration was achieved with no complications, and no recanalization was observed at the one-year follow-up in both cases. Coil embolization with jailed double-microcatheter technique following horizontal stenting is a safe and effective strategy for wide-necked bifurcation aneurysms.

Intraprocedural detection of cerebral hyperperfusion by flat detector computed tomography in the evaluation of cerebral blood volume during carotid artery stenting. A case report.

Cerebral blood volume (CBV) can be measured using a C-arm flat detector angiographic system. The present report describes a case in which cerebral hyperperfusion was detected with the Neuro parenchymal blood volume (PBV) system (syngo Neuro PBV IR, Siemens Medical Solutions, Erlangen, Germany) during carotid artery stenting (CAS). An 89-year-old man was referred to our hospital for cerebral brain infarction and severe stenosis of the left carotid artery. CAS was performed, and Neuro PBV was used to measure CBV both during and after the procedure. Postoperative Neuro PBV revealed dramatically increased CBV, and a hyperperfusion state was suspected. The next day, subarachnoid hemorrhage along the sulcus of the left hemisphere was revealed on computed tomography. Strict management of blood pressure was instituted just after the detection of hyperperfusion, and the patient was ultimately discharged from the hospital without any new neurological deficits. Neuro PBV has the advantage that it can be performed in the angiography suite and does not require patient transfer to an alternate setting. Therefore, intracranial hemodynamic changes can be detected during the procedure. We conclude that the Neuro PBV system is useful for monitoring intracranial hemodynamics during endovascular procedures.

Improving precise positioning of surgical robotic instruments by a three-side-view presentation system on telesurgery.

For faultless collaboration among the surgeon, surgical staffs, and surgical robots in telesurgery, communication must include environmental information of the remote operating room, such as behavior of robots and staffs, vital information of a patient, named supporting information, in addition to view of surgical field. "Surgical Cockpit System, " which is a telesurgery support system that has been developed by the authors, is mainly focused on supporting information exchange between remote sites. Live video presentation is important technology for Surgical Cockpit System. Visualization method to give precise location/posture of surgical instruments is indispensable for accurate control and faultless operation. In this paper, the authors propose three-side-view presentation method for precise location/posture control of surgical instruments in telesurgery. The experimental results show that the proposed method improved accurate positioning of a telemanipulator.

Immunogenicity of hylan g-f 20 in Guinea pigs and mice.

OBJECTIVE: To determine the product-specific immunogenicity of a chemically-modified sodium hyaluronate derivative, hylan G-F 20, that is used in the treatment of osteoarthritis of the knee. METHODS: Guinea pigs were subcutaneously immunized with hylan G-F 20 (Synvisc) once a week for 3 weeks. After resting, these animals received an intradermal challenge with hylan to elicit allergic skin reactions. Animal sera were tested for the presence of hylan-specific antibodies by homologous passive cutaneous anaphylaxis (PCA) assay and of anti-hylan IgG by ELISA. Further, mice were similarly immunized with hylan, and their sera were analyzed by heterologous PCA assay in rats and by ELISA for anti-hylan Ig(G+M) and anti-hylan IgE. RESULTS: In the guinea pig studies, acute and delayed erythematous skin reactions were elicited in immunized animals after the intradermal challenge with hylan. The sera of hylan-immunized guinea pigs showed positive reaction in the homologous PCA assay and significantly high amount of anti-hylan IgG, whereas the sera did not show any cross-reactivity against sodium hyaluronate. Hylan also exhibited immunogenicity in mice of 3 inbred strains, and C3H/HeN mice showed higher production of anti-hylan antibodies than Balb/c and C57BL/6 mice. CONCLUSION: Hylan G-F 20 exhibited immunogenicity in guinea pigs and mice. Recent reported severe acute inflammatory reactions in human patients after repeated intraarticular injections of hylan G-F 20 might involve product-specific, immune-mediated mechanisms.

A case of Vogt-Koyanagi-Harada disease with good visual acuity in spite of subfoveal fold.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease patients with the complication of subretinal pigmented proliferative tissue tend to have a poor visual prognosis. CASE: We herein report a case of VKH with good visual acuity despite a prominent subretinal fold. OBSERVATIONS: A 24-year-old woman, who experienced several recurrent episodes of VKH disease, had bilateral serous retinal detachment with poor vision (RE 20/40 and LE 20/25). After the administration of high doses of systemic corticosteroids and D-mannitol, the subretinal fluid disappeared and the sensory retinas gradually became reattached. During the course of therapy, prominent pigmented subretinal strands were formed in both eyes. Optical coherence tomography disclosed that the strands existed at the retinal pigment epithelium level. Amazingly, we observed a change in the location of the fold in the posterior retina during the course of the disease. The patient finally showed the "sunset glow" fundi and a subretinal fold that was located almost directly beneath both fovea. Fortunately, this patient was able to recover and finally achieve a good visual acuity (RE 20/17 and LE 20/17). CONCLUSION: We reported a VKH disease patient with a good visual acuity despite a remarkable subfoveal fold, which changed its location during the course of the disease.

Anti-CD23 monoclonal antibody inhibits germline Cepsilon transcription in B cells.

A chimeric macaque/human (PRIMATIZED) anti-CD23 antibody, p6G5G1, demonstrated a strong inhibitory effect on IL-4 and anti-CD40 antibody-stimulated IgE production by human peripheral blood mononuclear cells (PBMCs). RNA analysis by both reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot showed that p6G5G1 inhibited germline Cepsilon RNA synthesis, but had no effect on CD23 mRNA levels. These data suggest that p6G5G1 may inhibit immunoglobulin class switching to IgE through the inhibition of germline Cepsilon RNA synthesis. Early addition of p6G5G1 after stimulation by IL-4 and anti-CD40 was critical for IgE inhibition. In contrast, later addition of p6G5G1 still showed inhibition of increased levels of surface CD23, which is normally upregulated by stimulation with IL-4 and anti-CD40.