The HIV capsid mimics karyopherin engagement of FG-nucleoporins.

HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus1,2. Remarkably, the intact HIV capsid is more than 1,000 times larger than the size limit prescribed by the diffusion barrier of the nuclear pore3. This barrier in the central channel of the nuclear pore is composed of intrinsically disordered nucleoporin domains enriched in phenylalanine-glycine (FG) dipeptides. Through multivalent FG interactions, cellular karyopherins and their bound cargoes solubilize in this phase to drive nucleocytoplasmic transport4. By performing an in vitro dissection of the nuclear pore complex, we show that a pocket on the surface of the HIV capsid similarly interacts with FG motifs from multiple nucleoporins and that this interaction licences capsids to penetrate FG-nucleoporin condensates. This karyopherin mimicry model addresses a key conceptual challenge for the role of the HIV capsid in nuclear entry and offers an explanation as to how an exogenous entity much larger than any known cellular cargo may be able to non-destructively breach the nuclear envelope.

Successfully treated superficial basal cell carcinomas with ingenol mebutate 0.05% gel: Report of twenty cases.

Surgery is the therapy of choice in the guidelines to treat basal cell carcinomas (BCCs) but a variety of non-surgical options are available. The objective of this study is to evaluate the efficacy and safety of ingenol mebutate 0.05% gel for the treatment of superficial BCCs. We accepted twenty patients with superficial BCCs on the body and we treated them once daily for two consecutive days with ingenol mebutate 0.05% gel. We examined the lesions at the screening visit and after four days from the gel application to describe the local skin reaction due to the therapy. Then we followed the patients after two and six months from the first visit. All the lesions were clinically and dermoscopically documented with a digital camera and we used the LSR (local skin reaction) grading scale based on a 0-4 numerical index of severity with specific clinical parameters and a characteristic photographic image for each rating, to assess the local side effects related to the therapy.

The diagnosis of early psoriatic arthritis in an outpatient dermatological centre for psoriasis.

BACKGROUND: Most of the data currently available on early psoriatic arthritis (EPsA) derive from studies performed in rheumatological settings. However, in recent years, there has been an increase in the amount of data from dermatologic centres. OBJECTIVES: To describe the prevalence, clinical, laboratory and imaging characteristics of psoriatic patients with EPsA seen at a dermatological outpatient psoriasis centre. METHODS: From January 2007 to May 2010, all patients with psoriasis who visited the psoriasis centre were asked about inflammatory joint involvement. A diagnosis of psoriatic arthritis was made on the basis of clinical, laboratory and imaging studies. The patients were diagnosed with early PsA (EPsA) if their inflammatory articular symptoms had been present for ≤ 1 year. RESULTS: We diagnosed EPsA in 33 patients. Joint involvement was polyarticular (>5 joints involved) in 20 patients (60.6%) and oligoarticular (≤5 joints involved) in the remaining 13 patients. Quality of life due to skin involvement and the degree of functional impairment due to joint inflammation were only mildly affected, as measured by DLQI and HAQ, respectively. A direct correlation between the number of tender joints (ACR 68) and HAQ was found (r = 0.36; P = 0.04). Imaging studies showed that in spite of the absence of radiologic findings of peripheral joint damage, ultrasonography and contrast enhanced ultrasonography showed signs of articular inflammation in all patients. CONCLUSIONS: A diagnosis of EPsA can be correctly performed in a dermatologic outpatient facility. To do so, a close collaboration among dermatologists, rheumatologists and radiologists is necessary.

Pulmonary sarcoidosis in a patient with psoriatic arthritis during infliximab therapy.

The occurrence of sarcoidosis during anti-TNF-alpha therapy has occasionally been published. We report the case of a psoriasis patient who developed pulmonary sarcoidosis during a cycle of therapy with infliximab.

In vitro susceptibility of Pseudomonas mallei to antimicrobial agents.

Pseudomonas mallei was isolated from pus samples obtained from 34 mallein-positive horses. The isolates were subjected to in vitro sensitivity test using 16 different antimicrobial discs. All isolates (34) were sensitive to sulfamethizole, gentamycin, tetracycline, sulfathiazole, kanamycin, tobramycin, streptomycin and a combination of trimethoprim and sulfamethoxazole while none of them were sensitive to cephalothin, colistin, ampicillin, penicillin and nitrofurantoin. Rifapicin, chloramphenicol and carbenicillin were effective against 32, 26 and 18 isolates respectively. The minimum inhibitory concentrations (MICs) of gentamycin, tetracycline, tobramycin, sulfamethizole, streptomycin, rifampicin and a combination of trimethoprim and sulfamethoxazole were 0.28, 0.38, 0.67, 1.40, 3.40, 5.86 and 5.30 micrograms/ml, respectively.

Effect of Corynebacterium parvum on bone marrow macrophage colony production, peripheral blood leukocytes, and histologic changes of tissues in calves.

An IV injection of formalin-killed Corynebacterium parvum in calves did not cause a marked increase in the number of bone marrow macrophage colonies or peripheral blood monocytes, granulocytes, or lymphocytes. In treated calves, the spleen increased in weight and there were macrophage infiltrations in liver, lungs, spleen, and lymph nodes. Lymphoid hyperplasia was observed in bronchial-associated lymphoid tissue, cortical areas of the thymus, and in primary and secondary follicles and the paracortical area of lymph nodes.

Proliferative, morphologic, and cytochemical characteristics of bovine bone marrow macrophage colonies in liquid culture.

Bovine macrophage colonies were grown in liquid medium. Serum collected from a heifer 3 hours after injection of Pseudomonas aeruginosa endotoxin promoted the growth of macrophage colonies. The optimum concentration of postendotoxin serum was 16%. The numbers of colonies increased exponentially between 3 and 6 days of incubation and leveled off at 6 days. Monoblasts, promonocytes, and macrophages were observed in these colonies. A direct linear relationship between the number of nucleated bone marrow cells cultured and the number of colonies formed was found. The macrophage colony cells were positive for nonspecific esterase activity and were negative for chloroacetate esterase activity. Weak peroxidase activity was noticed in monoblasts, promonocytes, and occasionally in macrophages.

The kinetics of mononuclear phagocytes in normal calves given Corynebacterium parvum.

Two groups of calves, three in each group, were used to determine the kinetics of mononuclear phagocytes in normal calves and in calves given Corynebacterium parvum intravenously, using tritiated thymidine as an in vivo deoxyribonucleic acid label. In normal calves, the mean production time of labelled monocytes in the bone marrow was 36.4 +/- 2.04 hours. The turnover rate of labelled monocytes from the bone marrow into the peripheral blood was 5.4 +/- 0.3% per hour and the disappearance rate of labelled monocytes from the circulation was 0.9 +/- 0.3%. The half lives of labelled blood monocytes were 22.5 hours for cells with 16-30 grains and 19.5 hours for cells with 31-50 grains. Alveolar macrophages were derived from peripheral blood monocytes. In calves given C. parvum, the production time, turnover rate and half lives of labelled monocytes did not differ significantly (p greater than 0.05) from the values in normal calves.

Morphology and cytochemistry of bovine bone marrow mononuclear phagocytes.

Bone marrow samples were collected from five normal calves and mononuclear cells were separated using Ficoll-Hypaque. Mononuclear cells were cultured on coverslips in Leighton tubes for six hours. The adherent cells were differentiated using Wright's and nonspecific esterase stains. Monoblasts, promonocytes and monocytes were present in the proportion of 1:2.31:4.96.

The pulmonary clearance of Pasteurella haemolytica in calves given Corynebacterium parvum and infected with parainfluenza-3 virus.

Four control calves were aerosolized with parainfluenza-3 and one week later with Pasteurella haemolytica. Three calves were given Corynebacterium parvum at a dose of 15 mg/m2 body surface area, infected with parainfluenza-3 virus one week later, and aerosolized with P. haemolytica two weeks after C. parvum injection. All calves were killed four hours after P. haemolytica exposure and the bacterial retention in the lung was determined. Parainfluenza-3 viral infection did not exert any suppressive effect on pulmonary clearance of P. haemolytica in six out of seven calves used. However, the bacterial colony counts in the lungs of control calves were higher (P less than 0.05) than those in calves given C. parvum. Hence, C. parvum appeared to enhance bacterial clearance. Despite the marked influx of neutrophils into the lungs after the bacterial inoculation, the neutrophil:macrophage ratio in lavage samples was less in calves given C. parvum than in the control calves. The alveolar macrophages in C. parvum treated calves were generally larger but did not differ significantly (P less than 0.05) from those in the controls. There was no significant (P less than 0.05) correlation between the percentages of alveolar macrophages and the bacterial clearance. In calves given C. parvum, bacterial clearance was enhanced in those calves which had larger macrophages.

Selective killing of macrophages in the peritoneal cavity by carrageenan and its effect on normal infection of Eimeria tenella in chickens.

An in vivo method is described showing how selective killing of macrophages in the peritoneal cavity by carrageenan affects Eimeria tenella infection in chickens. Killing of macrophages was demonstrated by the increasing loss of cytoplasmic contents under light microscopy, by the disappearance of mitochondria and endoplasmic reticulum ultrastructurally, and by the about 10%-per-hr loss of nonspecific esterase activity as uptake of carrageenan increased. Heterophils were apparently unaffected. Effect of such a selective killing on E. tenella infection seemed to be greatest when the carrageenan was injected intraperitoneally 24 hr before oocyst inoculation per os, but effect after the oocysts were inoculated was minimal or nonexistent. That chickens injected with carrageenan twice (once 24 hr before and once 48 hr after E. tenella inoculation) showed higher lesion scores with 15,000 oocysts than the controls showed with 60,000 oocysts further demonstrated the participation of macrophages in E. tenella infection.