Polyhedron-like Inclusion Body Formation by a Mutant Nucleopolyhedrovirus Expressing the Granulin Gene from a Granulovirus

The polyhedrin gene inBombyx morinucleopolyhedrovirus (BmNPV) was replaced with the granulin gene ofTrichoplusia nigranulovirus (TnGV). The substitution was verified by Southern hybridization, and expression of granulin by the mutant virus, BmGran, was demonstrated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and by amino acid sequencing of the predominant protein of BmGran inclusion bodies (IBs). Light and electron microscopy examination of BmGran-infectedB. moriand BmN cells revealed large, cuboidal, polyhedron-like IBs in the nucleus and cytoplasm, but granules were not seen. IBs contained small, parallel, electron-dense streaks, which defined the geometric pattern of crystallization. Geometric patterns of nuclear IBs were frequently disrupted by occlusion of polyhedron envelope fragments, resulting in IB instability and fracturing. Virions were not embedded in most of the polyhedron-like IBs, but accumulated with polyhedron envelope fragments. Some virions were coated with matrix protein and were partially wrapped by polyhedron envelope. These results suggested that (1) the amino acid sequence of granulin is insufficient for determining IB morphology in TnGV-infected cells, and TnGV may have genes, not present in BmNPV, that control granule formation, and (2) interactions among the virion, the IB envelope, and the matrix protein may be important in virion occlusion and IB morphology and stability.     

ASO Author Reflections: Do Shorter Tumor-to-Nipple Distances Compromise the Local Oncologic Safety of Nipple-Sparing Mastectomy?

Annals of Surgical Oncology -     

Treatment of Recurrent Hemarthrosis Following Total Knee Arthroplasty Using Surgical Interventions

BackgroudRecurrent hemarthrosis following total knee arthroplasty (TKA) is a rare complication. Its pathophysiology and standard treatments have not yet been established. In this study, we report 7 cases of recurrent hemarthrosis after TKA in which failure of the initial conservative treatment was followed by angiographic embolization; in 1 of the 7 cases, arthroscopic electrocauterization was also performed after treatment failure with selective embolization.MethodsFrom January 2015 to May 2018, 7 patients visited our hospital due to recurrent hemarthrosis after TKA. Their medical records and serologic test results were reviewed to check for the presence of any bleeding disorder and history of anticoagulant use. Implant malalignment and instability were checked using X-ray. In all cases, the conservative treatment failed, so interventional angiography with selective embolization was performed, which was also followed by arthroscopic electrocauterization if the outcome was unsatisfactory.ResultsThe interval between TKA and the onset of hemarthrosis ranged from 3 to 76 months (average, 34.1 months). There was no coagulopathy and instability. All patients underwent conservative treatment at an interval of 4.3 months and the rate of relapse was 3.1 on average. On the interventional angiography, 6 cases showed vascular blush, and 1 case had pulsatile bleeding. The average duration for interventional angiography was 90.9 minutes. The average length of follow-up was 38.8 months. Embolization was successfully performed in 4 cases. In 2 of 3 failed cases, the symptoms improved without further treatment. In the remaining 1 failed case, the patient had a relapse of hemarthrosis, so an arthroscopic procedure was performed, which led to identification of the suspicious bleeding point by using preoperative angiographic findings. Electrocauterization was performed and active bleeding was stopped. All cases with recurrent hemarthrosis achieved improvement.ConclusionsInterventional angiography was used to aid in the diagnosis of recurrent hemarthrosis, and therapeutic selective embolization provided satisfactory clinical results. Even if selective embolization fails, interventional angiography may be helpful for further surgical procedures because it reveals vascular blush of a bleeding site. Therefore, interventional angiography and selective embolization should be considered to be a useful treatment for recurrent hemarthrosis after TKA.     

Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma

BACKGROUND: Chinese herbal medicine has a long history of human use. A novel herbal formula, anti-asthma herbal medicine intervention (ASHMI), has been shown to be an effective therapy in a murine model of allergic asthma. OBJECTIVE: This study was undertaken to compare the efficacy, safety, and immunomodulatory effects of ASHMI treatment in patients with moderate-severe, persistent asthma with prednisone therapy. METHODS: In a double-blind trial, 91 subjects underwent randomization. Forty-five subjects received oral ASHMI capsules and prednisone placebo tablets (ASHMI group) and 46 subjects received oral prednisone tablets and ASHMI placebo capsules (prednisone group) for 4 weeks. Spirometry measurements; symptom scores; side effects; and serum cortisol, cytokine, and IgE levels were evaluated before and after treatment. RESULTS: Posttreatment lung function was significantly improved in both groups as shown by increased FEV(1) and peak expiratory flow findings (P<.001). The improvement was slightly but significantly greater in the prednisone group (P<.05). Clinical symptom scores, use of beta(2)-bronchodilators, and serum IgE levels were reduced significantly, and to a similar degree in both groups (P<.001). T(H)2 cytokine levels were significantly reduced in both treated groups (P<.001) and were lower in the prednisone-treated group (P<.05). Serum IFN-gamma and cortisol levels were significantly decreased in the prednisone group (P<.001) but significantly increased in the ASHMI group (P<.001). No severe side effects were observed in either group. CONCLUSION: Anti-asthma herbal medicine intervention appears to be a safe and effective alternative medicine for treating asthma. In contrast with prednisone, ASHMI had no adverse effect on adrenal function and had a beneficial effect on T(H)1 and T(H)2 balance.     

Facilitating visuospatial attention for the contralateral hemifield by repetitive TMS on the posterior parietal cortex

Previous studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) could modulate the visuospatial functions. In this study, we investigated the effect of off-line high frequency subthreshold rTMS, when applied over the right or left posterior parietal cortex (PPC), on the visuospatial attention of the bilateral hemispaces. The subjects underwent visuospatial tasks before and immediately after receiving 1000 pulses of 10 Hz rTMS for a period of 20 min, and their responses were recorded. Our results demonstrated that the high frequency rTMS applied over the PPC produced facilitative effects on the visuospatial attention to the contralateral hemispace. The inhibitory effect to the ipsilateral hemispace was noticeable only in the left PPC.     

Induction of Alzheimer antigens by an uncoupler of oxidative phosphorylation

Since previous studies have suggested that the coupling of oxidation to phosphorylation is impaired in Alzheimer brain and fibroblasts, the effects of carbonyl cyanide m-chlorophenylhydrazone, a hydrazone known to uncouple mitochondrial oxidative phosphorylation, were tested on the development of immunoreactivity with antibodies to "Alzheimer antigens" in cultured fibroblasts from cognitively intact subjects. The fibroblasts were exposed for 10 to 14 days to a medium (DMd) modeled on media that favor neuronal differentiation in fetal brain cultures. The addition of a 10-microns concentration of carbonyl cyanide m-chlorophenylhydrazone to the DMd culture medium increased by more than 10-fold the proportion of cells reacting immunocytochemically with antibodies to paired helical filaments and by 157-fold the proportion of cells reacting with the Alz-50 monoclonal antibody. These observations suggest that the oxidative abnormalities previously described in tissues from patients with Alzheimer's disease may contribute to the accumulation of abnormal cytoskeletal materials in this disorder.     

Various medico-social aspects of children's disability in the Kirghiz SSR

Disability of children is an urgent, little investigated and medicosocial problem. It is characterised by high level, severity, very slow dynamics and stipulates the formation of population of "invalids from childhood" among adult population. The main causes of disability are congenital and genetic diseases, mainly neuropsychic. Hereditary factors, diseases during pregnancy, the use of drugs, consumption of alcohol, complicated delivery also play a major role. The lack of watchfulness both on the part of physicians and the parents themselves also results in the birth of affected children. Prevention priorities include medico-genetic counseling, the improvement of obstetric care and increasing awareness of the importance of family planning among young people. The disability of children should be regarded as an important qualitative indicator of joint activities of obstetrician-gynaecologists, general practitioners and pediatricians.     

Effect of hepatic cirrhosis on the pharmacokinetics of theophylline in rats

The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethylnitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life (t_1/2) in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL (8.67±4.85%) decreased about four-folds, but in DMNA (73.00±9.85%) similar result, was observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.     

Prevention of liver-tumor colonization by combined immunomodulation and liver lectin blocking

The protective effect of combined treatment (immunomodulation with Propionibacterium avidum KP-40; liver lectin blocking by D-galactose administration) on the liver colonization of RAW 117-H10 lymphosarcoma was investigated in BALB/c-mice. Both, immunomodulation with P. avidum KP-40 as well as liver lectin blocking by D-galactose treatment significantly decreased the number of liver tumor colonies in this experimental model. However, the combination of P. avidum KP-40 and D-galactose obviously proved to be superior to each monotherapy since the liver colonization by RAW 117-H 10 lymphosarcoma could be completely inhibited.     

PCNA immunostaining combined with AgNOR staining in esophageal squamous cell carcinoma to identify patients with a poor prognosis

Immunostaining of the proliferating cell nuclear antigen (PCNA) provides important information about cell kinetics and is easily performed on routinely obtained formalin-fixed, paraffin-embedded materials. We report herein the results of a retrospective study on PCNA staining in esophageal cancer undertaken to determine its significance. As this study indicated that immunoreactivity was preserved in specimens fixed within 24 h, only 31 specimens from surgical patients were available for this investigation. The mean PCNA index of the patients without invasion to the adventitia (35.7±17.9) was significantly lower than that of those with invasion to the adventitia or neighboring structures (49.7±14.5), while the PCNA index did not correlate with other clinicopathologic parameters such as histologic type, lymph node metastases, or prognosis. However, when an analysis of PCNA staining was combined with an analysis of argyrophilic nucleolar organizer region (AgNOR) staining, a correlation with prognosis was found. In fact, seven patients with a high PCNA index (44) and AgNOR count (6) had a significantly poorer prognosis than the remaining 22 (P=0.0014), and six of these seven patients died within 2 years. These results indicate that this combined evaluation may be useful for the identification of patients with a poor prognosis among those undergoing surgery for esophageal squamous cell carcinoma.