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Peripheral artery disease (PAD) and atrial fibrillation (AF) are associated with major cardiovascular and cerebrovascular events (MACCE). However, outcomes stratified according to the preoperative symptoms of PAD in patients with AF have not been sufficiently investigated. This was a retrospective study of prospectively collected data pertaining to 2237 patients (1179 patients with intermittent claudication [IC] and 1058 patients with critical limb-threatening ischemia [CLTI]) who underwent endovascular therapy at 34 hospitals between August 2014 and August 2016. AF was present in 91 (7.7%) patients with IC and 150 (14.2%) patients with CLTI. In the CLTI group, patients with AF had a higher event rate of MACCE and all-cause death than those without AF (1-year rates of freedom from MACCE: 0.66 and 0.81 in patients with and without AF, respectively, p < 0.001). In contrast, in the IC group, there was no statistically significant difference in the rates of MACCE between patients with and without AF. In the Cox multivariate analysis, AF was a significant predictor of MACCE in patients with CLTI but not in patients with IC, even after adjusting for covariates. The impact of AF on the outcome of patients with PAD was greater in those with CLTI. Further studies are needed to clarify the possible mechanisms underlying these differences., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: Contrast-enhanced computed tomography (CT) is commonly used to diagnose pulmonary embolism (PE). However, a history of iodine contrast allergy presents a dilemma in the management of patients with PE. As an alternative approach, X-ray fluoroscopic video analysis has been recently reported to be useful in diagnosing PE., Case Summary: A 78-year-old man with dyspnoea of 1-month duration visited our hospital. His oxygen saturation was 89%, and echocardiography demonstrated right heart strain. We could not perform contrast-enhanced CT because the patient had a history of contrast allergy and refused to undergo premedicated contrast CT with anti-histamine and/or corticosteroid. Therefore, a video analysis of pulmonary circulation using dynamic chest X-ray (DCR) was performed. The reconstructed pseudo-colour video showed defects of pulmonary circulation in both lung areas. We diagnosed PE and started anticoagulant therapy. Multiple segmental defects were also observed in pulmonary perfusion scintigraphy on Day 3, which confirmed the diagnosis of PE. He was discharged on Day 9, and an improvement of the pulmonary circulation as assessed with DCR was observed. He had no symptoms at the last follow-up visit at 1 year after discharge., Discussion: We describe the successful visualization of PE using DCR in a patient with iodine contrast allergy., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The affinity for K + of silkworm Na + /K + -ATPase, which is composed of α and β subunits, is remarkably lower than that of mammalian Na + /K + -ATPase, with a slightly higher affinity for Na + . Because the α subunit had more than 70% identity to the mammalian α subunit in the amino acid sequence, whereas the β subunit, a glycosylated protein, had less than 30% identity to the mammalian β subunit, it was suggested that the β subunit was involved in the affinities for Na + and K + of Na + /K + -ATPase. To confirm this hypothesis, we examined whether replacing the silkworm β subunit with the mammalian β subunit affected the affinities for Na + and K + of Na + /K + -ATPase. Cloned silkworm α and cloned rat β1 were co-expressed in BM-N cells, a cultured silkworm ovary-derived cell lacking endogenous Na + /K + -ATPase, to construct a hybrid Na + /K + -ATPase, in which the silkworm β subunit was replaced with the rat β1 subunit. The hybrid Na + /K + -ATPase increased the affinity for K + by 4.1-fold and for Na + by 0.65-fold compared to the wild-type one. Deglycosylation of the silkworm β subunit did not affect the K + affinity. These results support the involvement of the β subunit in the Na + and K + affinities of Na + /K + -ATPase., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The human Golgi/secretory pathway Ca 2+ ,Mn 2+ -ATPase 1 (hSPCA1) transports Ca 2+ and Mn 2+ into the Golgi lumen. Studies of the biological functions of hSPCA1 are limited by a lack of selective pharmacological tools for SPCA1 inhibition. The aim of this study was therefore to identify compounds that specifically inhibit hSPCA1 activity. We found that five 1,3-thiazole derivatives exhibited inhibitory action towards the ATP hydrolysis activity of hSPCA1a in a concentration-dependent manner. Among the derivatives tested, compound 1 was the most potent, completely inhibiting hSPCA1a activity with a half-maximal inhibition (IC 50 ) value of 0.8 μM. Compound 1 also partially inhibited the activity of another Ca 2+ ,Mn 2+ -ATPase (hSPCA2) and Ca 2+ -ATPase (rSERCA1a), but had no effect on Na + ,K + -ATPase or H + ,K + -ATPase. Treatment of HeLa cells with compound 1 led to fragmentation of the Golgi ribbon into smaller stacks. In addition, compound 1 mobilized intracellular Ca 2+ in HeLa cells that had been pre-treated with thapsigargin. Therefore, based on its selectivity and potency, compound 1 may be a valuable tool with which to further explore the role of SPCA1 in cellular processes., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The involvement of secretory pathways and Golgi dysfunction in neuronal cells during Alzheimer's disease progression is poorly understood. Our previous overexpression and knockdown studies revealed that the intracellular protein level of Syntaxin-5, an endoplasmic reticulum-Golgi soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE), modulates beta-amyloid precursor protein processing in neuronal cells. We recently showed that changes in endogenous Syntaxin-5 protein expression occur under stress induction. Syntaxin-5 was upregulated by endoplasmic reticulum stress but was degraded by Caspase-3 during apoptosis in neuronal cells. In addition, we showed that sustained endoplasmic reticulum stress promotes Caspase-3-dependent apoptosis during the later phase of the endoplasmic reticulum stress response in NG108-15 cells. In this study, to elucidate the consequences of secretory pathway dysfunction in beta-amyloid precursor protein processing that lead to neuronal cell death, we examined the effect of various stresses on endoplasmic reticulum-Golgi SNARE expression and beta-amyloid precursor protein processing. By using compounds to disrupt Golgi function, we show that Golgi stress promotes upregulation of the endoplasmic reticulum-Golgi SNARE Syntaxin-5, and prolonged stress causes Caspase-3-dependent apoptosis. Golgi stress induced intracellular beta-amyloid precursor protein accumulation and a concomitant decrease in total amyloid-beta production. We also examined the protective effect of the chemical chaperone 4-phenylbutylate on changes in amyloid-beta production and the activation of Caspase-3 induced by endoplasmic reticulum and Golgi stress. The compound alleviated the increase in the amyloid-beta 1-42/amyloid-beta 1-40 ratio induced by endoplasmic reticulum and Golgi stress. Furthermore, 4-phenylbutylate could rescue Caspase-3-dependent apoptosis induced by prolonged organelle stress. These results suggest that organelle stress originating from the endoplasmic reticulum and Golgi has a substantial impact on the amyloidogenic processing of beta-amyloid precursor protein and Caspase-3-dependent apoptosis, leading to neuronal cell death., (Copyright © 2022. Published by Elsevier Inc.)

In e-commerce settings, shoppers can navigate to product-specific pages on which they are asked to make yes-or-no decisions about buying a particular item. Beyond that target, there are often other products displayed on the page, such as those suggested by the retailers' recommendation systems, that can influence consumers' buying behavior. We propose that display items that come from the same category as the target product (matched) may enhance target purchase by increasing the attractiveness of the presented opportunity. Contrasting this, mismatched display items may reduce purchase by raising awareness of opportunity costs. Eye-tracking was used to explore this framework by examining how different types of displays influenced visual attention. Although target purchase rates were higher for products with matched vs. mismatched displays, there was no difference in fixation time for the target images. However, participants attended to mismatched display items for more time than they did for matched ones consistent with the hypothesized processes. In addition, increases in display attractiveness increased target purchase, but only for matched items, in line with supporting the target category. Given the importance of relative attention and information in determining the impact of display items, we replicated the overall purchase effect across varying amounts of available display information in a second behavioral study. This demonstration of robustness supports the translational relevance of these findings for application in industry., Competing Interests: SH is currently affiliated with a program run by Antler. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Karmarkar, Carroll, Burke and Hijikata.)

Background: Coronary artery fistulas are rare and most commonly asymptomatic; however, they can become enlarged and rupture in some cases., Case Summary: We report a case of a 51-year-old woman who was brought to our hospital unconscious in an ambulance. Cardiac tamponade caused by the rupture of an aneurismal coronary-pulmonary artery fistula (CPAF) was detected by contrast-enhanced computed tomography and confirmed by invasive coronary angiography. Due to prompt diagnosis and subsequent surgical intervention, the patient's condition was rapidly improved, and she was discharged from the hospital., Discussion: Coronary-pulmonary artery fistula aneurysm rupture requires rapid diagnosis and treatment, and thus, in cases with cardiac tamponade and coronary aneurysm, CPAF aneurysm rupture should be considered., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) implanted with implantable cardioverter-defibrillators (ICDs) may show a large decrease in R-wave amplitude during long-term follow-up. However, it is unclear whether this decrease is higher in these patients than in those without structural heart disease. This study investigated ICD-lead intracardiac parameters over a long duration in patients with ARVC and HCM and compared these parameters with those of a control group. We included 50 patients (mean age, 55.2 ± 17.2 years; 26% female) with ICD leads in the right ventricular apex, and compared 7 ARVC and 14 HCM patients with 29 control patients without structural heart disease. ICD-lead parameters, including R-wave amplitude, pacing threshold, and impedance during follow-up, were compared. The difference in these parameters between the time of implantation and year 5 were also compared. There were no significant differences in R-wave amplitude at implantation among the 3 groups. The change in R-wave amplitude between the time of implantation and year 5 was significantly greater in the ARVC group (-3.3 ± 5.4 mV, P = 0.012) in comparison to the control group (1.3 ± 2.8 mV); the HCM group showed no significant difference (-0.4 ± 2.3 mV, P = 0.06). Thus, in the ARVC group, R-wave amplitude at year 5 was significantly lower than that in the control group (5.7 ± 4.8 mV versus 12.5 ± 4.5 mV, P = 0.001). In ARVC patients with ICDs, ventricular sensing is likely to deteriorate during long-term follow-up; however, in HCM patients, sensing may not deteriorate.

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Syphilitic aortitis might coexist in a dysfunctional aortic valve, but the etiology remains unclear, because microbiological diagnosis is difficult. A 62-year-old man with low-grade fever was diagnosed with aortitis and infective endocarditis, due to Treponema pallidum infection, using polymerase chain reaction analysis. This case suggests that syphilis might cause infective endocarditis., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Japan is facing problems associated with "heart failure (HF) pandemics" and bed shortages in core hospitals that can accommodate patients with acute HF. The prognosis is currently unknown for acute HF patients who were transferred from core hospitals to collaborating hospitals during the very early treatment phase and whose treatment strategies are in place.We enrolled 166 acute HF patients who were hospitalized between January 1, 2015, and December 31, 2015, and compared the conditions of transferred patients (n = 53, median duration before transfer = 6 days) and nontransferred patients (n = 113). The transferred and nontransferred patients had similar one-year mortality rates (24.5% versus 19.5%, log-rank P = 0.27) and composite one-year mortality and HF readmission rates (35.8% versus 31.0%, log-rank P = 0.32). Multivariate analysis determined that patient transfers were not associated with a higher composite endpoint (hazard ratio, 1.08; 95% confidence interval, 0.58-1.99, P = 0.82). Transferred patients with low composite congestion scores (CCSs) had significantly lower composite endpoints than those with high CCSs (23.5% versus 57.9%, log-rank P = 0.005).Acute HF patients who were transferred did not have inferior prognoses compared with nontransferred patients when the treatment strategies were correctly assumed by cardiologists. The implementation of early and strict decongestion strategies before transfer may be important for reducing cardiovascular events.

Background: Oral anticoagulants, including direct oral anticoagulants (DOACs), are usually required in atrial fibrillation (AF) patients who are at a high risk of thromboembolism (TE), even if they had undergone catheter ablation (CA). Although several studies have reported the safety and efficacy of DOACs around CA in AF patients, there are only limited data regarding the midterm incidence of TE and bleeding complications post-CA among AF patients treated with warfarin or DOACs., Methods: We studied 629 AF patients (mean age: 65.3 ± 10.3 years; 442 men) undergoing CA, to calculate the midterm incidence of TE and bleeding complications associated with warfarin or DOACs., Results: In total, 292 patients used warfarin and 337 used DOACs (dabigatran: 90 patients; rivaroxaban: 137; and apixaban: 110). At baseline, the CHA2DS2-VASc and HAS-BLED scores were similar between the 2 groups. During a median follow-up period of 7 months, no TE complications occurred. The warfarin group had a significantly higher bleeding event rate than did the DOACs group (all bleeding complications: 32 [11.0%] vs 15 [4.5%], respectively, P  = .002). The rate of all bleeding complications was significantly higher in the warfarin group than in the DOACs group (10.1% vs 3.7%, respectively, at 10 months; P  = .024). In Cox proportional hazards modeling, DOAC use was significantly associated with a decreased risk of bleeding (adjusted hazard ratio: 0.497; 95% confidence interval: 0.261-0.906, P  = .022)., Conclusions: Direct oral anticoagulant use in AF patients undergoing CA may be associated with a similar risk of TE as warfarin but is associated with a lower risk of bleeding.

Guideline-directed medical therapy (GDMT) is recommended for patients with heart failure with reduced ejection fraction (HFrEF). However, the prognostic impact of medication optimization at the time of discharge in patients hospitalized with heart failure (HF) is unclear. We analyzed 534 patients (73 ± 13 years old) with HFrEF. The status of GDMT at the time of discharge (prescription of angiotensin converting enzyme inhibitor [ACE-I]/angiotensin receptor blocker [ARB] and β blocker [BB]) and its association with 1-year all-cause mortality and HF readmission were investigated. Patients were divided into 3 groups: those treated with both ACE-I/ARB and BB (Both group: n = 332, 62%), either ACE-I/ARB or BB (Either group: n = 169, 32%), and neither ACE-I/ARB nor BB (None group: n = 33, 6%), respectively. One-year mortality, but not 1-year HF readmission rate, was significantly different in the 3 groups, in favor of the Either and Both groups. A favorable impact of being on GDMT at the time of discharge on 1-year mortality was retained even after adjustment for covariates (Either group: hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.21 to 0.90, p = 0.025 and Both group: HR 0.29, 95% CI 0.13-0.65, p = 0.002, vs None group). For 1-year HF readmission, no such association was found. In conclusion, optimization of GDMT before the time of discharge was associated with a lower 1-year mortality, but not with HF readmission rate, in patients hospitalized with HFrEF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A 55-year-old man presented with dyspnea, edema, and appetite loss. He had undergone coronary artery bypass grafting 8 years previously. He had jugular venous distention and Kussmaul's sign. Contrast-enhanced cardiac magnetic resonance imaging (CMRI) demonstrated an intrapericardial mass compressing the right ventricular (RV) cavity. T1- and T2-weighted black-blood images showed a mass with heterogeneous high signal intensity and a thick and dark rim. The mass was considered to be a chronic hematoma. After pericardiotomy with surgical removal of the hematoma, CMRI showed the marked improvement of the RV function. Late intrapericardial hematoma is rare and CMRI is useful for making a differential diagnosis.

Pericardiocentesis is a definitive strategy to remove pericardial effusion. In this report, we present a rare case of a 23-year-old man with sudden delayed hemorrhagic shock due to branch bleeding of the left internal thoracic artery (LITA) two days after undergoing pericardiocentesis. Angiography, embolization, and drainage were effective. As far as we know, this is the first report that shows delayed bleeding due to branch injury of the LITA as a possible complication after pericardiocentesis. < Learning objective: Pericardiocentesis using an apical approach under echocardiography is considered safe; however, in this case, unexpected complications after pericardiocentesis for hemorrhagic shock occurred. Patients who undergo pericardiocentesis should be observed in the hospital for several days. If sudden changes in vital signs occur, the underlying complications should also be considered, and it is important to act promptly and review the patient's prior procedures.>.

Objective : Although deep vein thrombosis (DVT) followed by pulmonary thromboembolism (PE) is a critical complication during pregnancy, there have been few reports about its intrapartum management. We evaluated intrapartum management by using a temporary inferior vena cava filter (IVCF) in pregnant women with PE/DVT. Materials and Methods : Eleven women with PE/DVT during pregnancy between January 2004 and December 2016 were included. The patients were hospitalized for intravenous unfractionated heparin infusion after acute PE/DVT onset. Seven patients were discharged and continued treatment with subcutaneous injection of heparin at the outpatient unit. IVCF was implanted 1-3 days before delivery in 10 patients. Anticoagulant therapy was discontinued 6-12 h before delivery. We retrospectively analyzed rates of maternal or perinatal death, and recurrence of symptomatic PE/DVT. Results : One patient was diagnosed as having PE/DVT and 10 had DVT alone. One patient suffered hemorrhagic shock during delivery; however, maternal or perinatal death and recurrence of symptomatic PE/DVT did not occur in any patient. Conclusion : Maternal or perinatal death and recurrence of symptomatic PE/DVT was not seen in women diagnosed as having PE/DVT during pregnancy and treated with anticoagulant therapy and IVCF.

Objective : To assess the safety and efficacy of edoxaban for the treatment of venous thromboembolism (VTE) secondary to active malignancy. Materials and Methods : We enrolled 48 patients with newly diagnosed VTE secondary to active malignancy that was treated with oral edoxaban for 1 year between September 2014 and August 2015. We retrospectively examined the presence or absence of recurrent symptomatic VTE, VTE-related mortality, and bleeding events. Results : No recurrent symptomatic VTE or VTE-related deaths were recorded, enabling efficient assessment. Treatment safety was determined based on the reports of bleeding. Bleeding was reported in two patients, with serious bleeding in one of them. Conclusion : Edoxaban is safe and effective for the treatment of VTE secondary to active malignancy.

We report a unique case of recurrent thromboembolism and its histological findings that were revealed in an autopsy. Although it is well known that repeating thrombosis presents organization and recanalization, we also observed rare findings of thickening of the bronchial artery and fixation of the valve of the lower extremity vein in this case., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The prognosis of super-elderly patients (age≥85 years) who undergo bradycardia pacemaker (PM) implantation remains unknown., Methods: We retrospectively enrolled 868 patients (men 49.0%, 76.6±10.6 years) who could walk unassisted and whose expected life expectancy was more than 1 year, receiving their first bradycardia PM implantation between January 1, 2006, and June 30, 2013. Clinical outcomes were compared between super-elderly patients (n=201, mean age 88.6±3.2 years) and younger patients (n=667, 73.0±9.3 years)., Results: At the end of a median 1285-day follow-up, 128 patients (14.7%) died, of which 54 were cardiac deaths (42.2%). Mortality rates were similar between the groups (16.4% vs. 14.2%, log-rank p=0.56) and across different indications for implantation (atrio-ventricular conduction disturbance or sick sinus syndrome, p=0.59), initial rhythms (sinus rhythm or persistent atrial fibrillation, p=0.62), pacing modes (dual chamber pacing or VVI pacing, p=0.26), and ventricular lead positions (septum or apex, p=0.52). On Cox proportional hazard model analysis, hypertension [hazard ratio (HR)=1.74, 95% confidence interval (CI)=1.19-2.54, p=0.004], diabetes mellitus (HR=2.18, 95% CI=1.51-3.14, p<0.001), history of myocardial infarction (HR=3.59, 95% CI=2.49-5.16, p<0.001), and history of stroke (HR=2.26, 95% CI=1.51-3.37, p<0.001) were independent predictors for mortality., Conclusions: The mortality rate of super-elderly patients who had no critical illnesses and were healthy enough to walk unassisted at the time of PM implantation was not inferior to that of younger patients. Prognosis was determined by comorbidities, but not by age, PM indication, initial rhythm, pacing leads, or mode., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

A membrane-anchored cytochrome c-550, which is highly expressed in obligately alkaliphilic Bacillus clarkii K24-1U, was purified and characterized. The protein contained a conspicuous sequence of Gly(22)-Asn(34), in comparison with the other Bacillus small cytochromes c. Analytical data indicated that the original and lipase-treated intermediate forms of cytochrome c-550 bind to fatty acids of C(15), C(16) and C(17) chain lengths and C(15) chain length, respectively, and it was considered that these fatty acids are bound to glycerol-Cys(18). Since there was a possibility that the presence of a diacylglycerol anchor contributed to the formation of dimeric states of this protein (20 and 17 kDa in SDS-PAGE), a C18M (Cys(18) --> Met)-cytochrome c-550 was constructed. The molecular mass of the C18M-cytochrome c-550 was determined as 15 and 10 kDa in SDS-PAGE and 23 kDa in blue native PAGE. The C18M-cytochrome c-550 bound with or without Triton X-100 formed a tetramer as the original cytochrome c-550 bound with Triton X-100, as determined by gel filtration. The midpoint redox potential of cytochrome c-550 as determined by redox titration was +83 mV, while that determined by cyclic voltammetric measurement was +7 mV. The above results indicate that cytochrome c-550 is a novel cytochrome c.

Study Design: Histologic changes in the spinal cord caused by progressive spinal kyphosis were assessed using a new animal model., Objectives: To evaluate the effects of chronic compression associated with kyphotic deformity of the cervical spine on the spinal cord., Summary of Background Data: The spinal cord has remarkable ability to resist chronic compression, however, delayed paralysis is sometimes seen following the development of spinal kyphosis. In the past, no animal model to clarify the mechanism of spinal cord damage due to spinal kyphotic deformity has been available., Methods: Laminectomy and bilateral facetectomy at the C4-C5 level was performed in 52 Japanese small game fowls. Histologic changes in the spinal cord associated with progressive kyphotic deformity were examined at different time points after surgery in each animal. The degree of spinal cord flattening and the severity of demyelination in histologic sections were quantitatively evaluated using an image analyzer, and their association with the kyphotic angle was analyzed. Changes in the microvascular distribution in the spinal cord were also examined by microangiography., Results: In all operated animals, progressive kyphosis developed reproducibly. The kyphotic angle increased gradually until 3 weeks after surgery and stabilized thereafter. There was a significant correlation between the kyphotic angle and the degree of spinal cord flattening. The spinal cord was compressed most intensely at the apex of the kyphosis, where demyelination of the anterior funiculus as well as neuronal loss and atrophy of the anterior horn were observed. Demyelination progressed as the kyphotic deformity became more severe, initially affecting the anterior funiculus and later extending to the lateral and then the posterior funiculus. Angiography revealed a decrease of the vascular distribution at the ventral side of the compressed spinal cord., Conclusions: Progressive kyphosis of the cervical spine resulted in demyelination of nerve fibers in the funiculi and neuronal loss in the anterior horn due tochronic compression of the spinal cord. These histologic changes seem to be associated with both continuous mechanical compression and vascular changes in the spinal cord.

Biodegradable microspheres were prepared through glutaraldehyde cross-linking of gelatin without using any surfactants as a carrier matrix of basic fibroblast growth factor (bFGF). In the in vitro system, bFGF was sorbed to microspheres of acidic gelatin with an isoelectric point (IEP) of 5.0, but not to those of basic gelatin with an IEP of 9.0. The rate of bFGF sorption to the acidic gelatin microsphere in phosphate-buffered saline solution (pH 7.4) was smaller than that in water. Following incorporation of bFGF into the microspheres at 4 degrees C for 12 h, bFGF release from the bFGF-incorporating microspheres was studied. Approximately 30% of incorporated bFGF was released from the acidic gelatin microsphere within the initial 3 h, followed by no substantial release, whereas the basic gelatin microsphere released almost completely the incorporated bFGF within 1 day. It is likely that when basic bFGF molecules were immobilized to the acidic gelatin constituting microspheres through polyion complexation, they were not readily released under the in vitro nondegradation condition of gelatin. Incorporation of anionic carboxylmethyl cellulose (CMC) into the acidic gelatin microspheres reduced the amount of bFGF desorbed initially. This indicates that the initial burst is ascribed to free bFGF which is not ionically interacted with the acidic gelatin. CMC will function as a bFGF sorbent to suppress the initial leakage from the microspheres. When injected subcutaneously into the mouse back, bFGF-incorporating acidic gelatin microspheres were degraded over time and induced neovascularization around the injection site, in marked contrast to bFGF in the solution form. CMC incorporation slowed down the biodegradation and vascularization effect of bFGF-incorporating gelatin microspheres. It was concluded that the gelatin microsphere was a promising carrier matrix of bFGF to enhance the vascularization effect.

S-antigen or interphotoreceptor retinoid-binding protein (IRBP), when injected with Freund's complete adjuvant into mice, does not easily cause experimental autoimmune uveoretinitis (EAU). In this report, we describe the results of injecting IRBP with Freund's complete adjuvant, together with the intraperitoneal administration of Bordetella pertussis, into several types of congenic mice (B10, B10A, B10BR, B10D2). These congenic mice, of C57BL/10 (B10) origin, differ at the H-2 locus on chromosome 17. We were able to produce EAU in 38.5% of B10A mice, and 12.5% of B10BR mice, confirming that EAU can develop in these mice that carry the k genotype at the K, I-A, and I-E regions of the major histocompatibility complex (MHC) H-2 locus. We believe that the k genotype of the K, I-A, and I-E regions is important as a factor in the pathogenesis of EAU in congenic B10 mice.

The water-insoluble aluminium salt of beta-cyclodextrin sulphate (Al.beta-CyD-Sul) was used as a stabilizer and sustained-release carrier for recombinant human basic fibroblast growth factor (bFGF). An adsorbate of bFGF with Al.beta-CyD-Sul was prepared by incubating the protein with a suspension of Al.beta-CyD-Sul in water. The mitogenic activity of bFGF released from the adsorbate, as indicated by the proliferation of kidney cells of baby hamster (BHK-21), was almost comparable with that of the intact bFGF. Al.beta-CyD-Sul significantly protected bFGF from proteolytic degradation by pepsin and alpha-chymotrypsin, compared with the water-soluble sodium salt. The in-vitro release of bFGF from the adsorbate was sustained in proportion to a rise in the ratio of Al.beta-CyD-Sul to the protein in the adsorbate. Of the bFGF preparations evaluated, the adsorbate of bFGF with Al.beta-CyD-Sul, when given subcutaneously to the rat, showed the most prominent increase in the formation of granulation tissues, due to the stabilization and slow-release of the mitogen. The limited data presented here suggest that the adsorbate of bFGF with Al.beta-CyD-Sul has a potent therapeutic efficacy for wound healing, and may be applicable to oral protein formulations for the treatment of intestinal mucosal erosions.

We studied the pathogenesis of IRBP-induced experimental autoimmune uveoretinitis (EAU) by immunohistochemical detection of various immune cells using specific monoclonal antibodies to their surface markers and adhesion molecules. The following results were obtained: (1) During each stage of EAU, CD4 positive T cells predominated over CD8 positive T cells in the retina and the uvea. (2) One day prior to the clinical onset of disease, la positive cells began to appear in the ciliary body. (3) LFA-1 and ICAM-1 were expressed on intraocularly infiltrating cells. (4) ICAM-1 was also expressed on endothelial cells of uveal and retinal vessels. In addition, ICAM-1 was expressed on ciliary body epithelium and retinal pigment epithelium, a finding which may be associated with the breakdown of the blood-ocular barrier. In conclusion, the expression of LFA-1 and ICAM-1 in EAU demonstrates that adhesion molecules, such as these, play an important role in inflammatory ocular disease in vivo.

The present study was designed to assess the validity of the Torque Test as a measure of functional lateral dominance in children. One hundred forty-nine children were administered the Torque Test and The Harris Test of Lateral Dominance. A low but statistically significant correlation was found between torque and total lateral dominance.

Lumbar disc herniations and degenerations are very prevalent lesions, and many surgical approaches have been adopted for these conditions. However, the results of conventional or extensive operations have not always been satisfying. In 1975, the author developed the technique of percutaneous nucleotomy in an effort to avoid the major surgeries then employed. Fenestration of the annulus and partial resection of the nuclear substance are achieved percutaneously by a posterolateral approach. Intradiscal pressure is reduced considerably, and relief of irritation of the nerve root or the pain receptors around the disc is obtained. The extraction of the herniated portion of the disc is not achieved by the procedure. However, the amount of herniated disc substance may be reduced by disc decompression with suction. The procedure can be done in a radiology department under local anesthesia and requires 30 to 60 minutes. Of 136 cases followed, 72% of the patients are satisfied. The concept and theoretical considerations, surgical instruments, details of improved technique, results, and complications of percutaneous nucleotomy are introduced and compared with the original technique.