Activity of a novel 1,3-beta-D-glucan Synthase Inhibitor, Ibrexafungerp (formerly SCY-078), Against Candida glabrata.

Ibrexafungerp (formerly SCY-078), a novel glucan synthase inhibitor with oral availability, was evaluated for activity against Candida glabrata Susceptibility of clinical strains to Ibrexafungerp was determined by microdilution and time kill assays. The MIC range against wild type strains was 1-2 µg/mL. IBX was also active against the majority of echinocandin-resistant strains. Time kill studies showed a 4 to 6-log reduction in growth at concentrations of 0.25 to 4 µg/ml at 24 and 48 hr.

The importance of international collaboration for rare diseases research: a European perspective.

Over the last two decades, important contributions were made at national, European and international levels to foster collaboration into rare diseases research. The European Union (EU) has put much effort into funding rare diseases research, encouraging national funding organizations to collaborate together in the E-Rare program, setting up European Reference Networks for rare diseases and complex conditions, and initiating the International Rare Diseases Research Consortium (IRDiRC) together with the National Institutes of Health in the USA. Co-ordination of the activities of funding agencies, academic researchers, companies, regulatory bodies, and patient advocacy organizations and partnerships with, for example, the European Research Infrastructures maximizes the collective impact of global investments in rare diseases research. This contributes to accelerating progress, for example, in faster diagnosis through enhanced discovery of causative genes, better understanding of natural history of rare diseases through creation of common registries and databases and boosting of innovative therapeutic approaches. Several examples of funded pre-clinical and clinical gene therapy projects show that integration of multinational and multidisciplinary expertize generates new knowledge and can result in multicentre gene therapy trials. International collaboration in rare diseases research is key to improve the life of people living with a rare disease.

Evaluation of the Efficacy of ME1111 in the Topical Treatment of Dermatophytosis in a Guinea Pig Model.

The treatment of dermatophytoses, including onychomycosis, has come a long way over the past few decades with the introduction of oral antifungals (e.g., terbinafine and itraconazole). However, with these advancements in oral therapies come several undesirable effects, such as kidney and liver toxicity, along with drug-drug interactions. Consequently, there is a need for new topical agents that are effective against dermatophytosis. ME1111 is a topical antifungal under development. In this study, thein vivoefficacy of ME1111 was compared to that of ciclopirox in the topical treatment of dermatophytosis caused byTrichophyton mentagrophytesusing a guinea pig model. Animals were treated with the topical antifungals starting at 3 days postinfection, with each agent being applied once daily for seven consecutive days. After the treatment period, the clinical and mycological efficacies were evaluated. The data showed that both antifungals demonstrated significant clinical and mycological efficacies; however, ME1111 showed clinical efficacy superior to that of ciclopirox (46.9% and 25.0%, respectively, with aPvalue of <0.001). The potent efficacy of ME1111 could be attributed to its properties, such as low keratin binding.

Anterior cruciate ligament injury about 20 years post-treatment: A kinematic analysis of one-leg hop.

Reduced dynamic knee stability, often evaluated with one-leg hops (OLHs), is reported after anterior cruciate ligament (ACL) injury. This may lead to long-standing altered movement patterns, which are less investigated. 3D kinematics during OLH were explored in 70 persons 23 ± 2 years after ACL injury; 33 were treated with physiotherapy in combination with ACL reconstruction (ACL(R)) and 37 with physiotherapy alone (ACL(PT)). Comparisons were made to 33 matched controls. We analyzed (a) maximal knee joint angles and range of motion (flexion, abduction, rotation); (b) medio-lateral position of the center of mass (COM) in relation to knee and ankle joint centers, during take-off and landing phases. Unlike controls, ACL-injured displayed leg asymmetries: less knee flexion and less internal rotation at take-off and landing and more lateral COM related to knee and ankle joint of the injured leg at landing. Compared to controls, ACL(R) had larger external rotation of the injured leg at landing. ACL(PT) showed less knee flexion and larger external rotation at take-off and landing, and larger knee abduction at Landing. COM was more medial in relation to the knee at take-off and less laterally placed relative to the ankle at landing. ACL injury results in long-term kinematic alterations during OLH, which are less evident for ACL(R).

Anterior cruciate ligament injury after more than 20 years: I. Physical activity level and knee function.

Little is known about physical activity level and knee function including jump capacity and fear of movement/reinjury more than 20 years after injury of the anterior cruciate ligament (ACL). Seventy persons with unilateral ACL injury participated (23 ± 2 years post-injury): 33 treated with physiotherapy in combination with surgical reconstruction (ACLR ), and 37 treated with physiotherapy alone (ACLPT ). These were compared with 33 age- and gender-matched controls. Assessment included knee-specific and general physical activity level [Tegner activity scale, International Physical Activity Questionnaire (IPAQ)], knee function [Lysholm score, Knee injury and Osteoarthritis Outcome Score (KOOS)], jump capacity (one-leg hop, vertical jump, side hops), and fear of movement/reinjury [Tampa Scale for Kinesiophobia (TSK)]. Outcomes were related to degree of osteoarthritis (OA). ACL-injured had lower Lysholm, KOOS, and Tegner scores than controls (P < 0.001), while IPAQ score was similar. ACL-injured demonstrated inferior jump capacity in injured compared with noninjured leg (6-25%, P < 0.001-P = 0.010 in the different jumps), while noninjured leg had equal jump capacity as controls. ACL groups scored 33 ± 7 and 32 ± 7 of 68 on TSK. Lower scores on Lysholm and KOOS symptom were seen for persons with moderate-to-high OA than for no-or-low OA, while there were no differences for physical activity and jump capacity. Regardless of treatment, there are still negative knee-related effects of ACL injury more than 20 years later.

Anterior cruciate ligament injury after more than 20 years. II. Concentric and eccentric knee muscle strength.

The long-term consequences on knee muscle strength some decades after rupture of the anterior cruciate ligament (ACL) are not established. The aims of our study were to examine peak torque more than 20 years after ACL injury and to compare their knee muscle strength to that of healthy controls. We tested 70 individuals with unilateral ACL injury 23 ± 2 years after injury, whereof 33 (21 men) were treated with physiotherapy in combination with ACL reconstruction (ACLR ) and 37 (23 men) with physiotherapy alone (ACLPT ). These were compared with 33 age- and gender-matched controls (21 men). A Kin-Com(®) dynamometer (90°/s) was used to measure peak torque in knee flexion and extension in both concentric and eccentric contractions. Knee extension peak torque, concentric and eccentric, was ∼10% lower for the injured leg compared with the non-injured leg for both ACLR (P < 0.001; P < 0.001) and ACLPT (P = 0.007; P = 0.002). The ACLPT group also showed reduced eccentric knee flexion torque of the injured leg (P = 0.008). The strength of the non-injured leg in both ACL groups was equal to that of controls. No difference was seen for those with no-or-low degree of knee osteoarthritis compared to those with moderate-to-high degree of osteoarthritis. ACL injury may lead to a persistent reduction of peak torque in the injured leg, which needs to be considered across the lifespan.

Reliability and validity of surface EMG assessments combined with isometric muscle strength testing in patients with abdominal rectus diastasis and asymptomatic controls.

PURPOSE: Patients with abdominal rectus diastasis (ARD) may have muscular functional impairments, but clinics lack appropriate objective assessment tools. The aim was to establish the relative and absolute reliability, and convergent validity, of muscular activity using Surface Electromyography (SEMG) during isometric abdominal muscle strength testing in patients with ARD and controls without ARD. METHODS: Twenty-six patients with ARD were matched for age, sex and BMI with controls without ARD. Participants were tested twice during isometric muscular contractions using SEMG located on six abdominal sites. Mean amplitude, fatigue, and recruitment order were analyzed. Relative reliability was evaluated with Intraclass Correlation Coefficients (ICC), while absolute reliability was estimated by calculating the Standard Error of Measurement and Minimal Detectable Change. Convergent validity was addressed in relation to participant characteristics, functional ability, and symptoms. RESULTS: Mean SEMG amplitude for all abdominal wall muscle contractions showed moderate to excellent relative test-retest reliability, with ICC values ranging from 0.46 to 0.97. In contrast, fatigue and recruitment order displayed poor to moderate relative reliability in both groups. Absolute reliability measures were generally high. A moderate to high convergent validity (ARD: rho-value 0.41-0.70; Controls: rho-value 0.41-0.75) was observed for mean amplitude in relation to a functional sit-to-stand test, abdominal circumference, BMI, back pain, and quality-of-life. CONCLUSIONS: The results of applying SEMG during isometric abdominal muscle support practicing the method in clinics, although additional development is needed with further standardization and more functional testing. Furthermore, the method demonstrates construct validity in patients with ARD and in age- and sex-matched controls.

New geochronological constraints on the thermal and exhumation history of the Lesser and Higher Himalayan Crystalline Units in the Kullu-Kinnaur area of Himachal Pradesh (India).

New geochronological, petrological and structural data from the Beas-Sutlej area of Himachal Pradesh (India) are used to reconstruct the tectonothermal and exhumation history of this part of the Himalayan orogen. Sm-Nd garnet ages at 40.5 ± 1.3 Ma obtained on a pegmatoid from the inverse metamorphic High Himalayan Crystalline (HHC) in the Malana-Parbati area probably mark local melting during initial decompression. Ongoing exhumation in ductilely deformed leuco-gneiss is constrained by Sm-Nd garnet ages at 29 ± 1 Ma and white mica Rb-Sr ages around 24-20 Ma, while Bt Rb-Sr ages indicate a drop of regional metamorphic temperatures below 300 °C between 15 and 12 Ma. The deep Sutlej gorge exposes medium-grade paragneisses and Proterozoic orthogneisses of the Lesser Himalayan Crystalline (LHC), overthrust by the HHC along the Main Central Thrust (MCT). Mica cooling ages in the HHC are in the range of 14-11 Ma. Above the extruded wedge of the HHC, the Leo Pargil leucogranite and associated dykes intrude the Haimanta Unit (HU) below the weakly metamorphic Palaeo-Mesozoic sediments of the Tethyan Himalayas (TH). The Leo Pargil leucogranite yielded a mean Sm-Nd garnet age of 19 ± 1 Ma and Rb-Sr muscovite and biotite cooling ages between 16.4 and 11.6 Ma. Marked young extrusion of LHC units resulted in differentiated exhumation/cooling of more frontal parts of the orogen. Very young ductile deformation of LHC gneisses near Wangtu is constrained by late-kinematic pegmatite intrusions crosscutting the main mylonitic foliation. Sm-Nd garnet and Rb-Sr muscovite ages of these pegmatites range between 7.9 ± 0.9 and 5.5 ± 0.1 Ma. Published apatite FT ages down to 0.6 Ma also document accelerated diachronous sub-recent exhumation of different parts of the orogen. Together with geochronological data from the literature, the new results demonstrate that the HHC and the HU were deformed by shortening and crustal thickening during the Eohimalayan phase (Late Eocene-Oligocene), followed by a strong thermal overprint and intrusions of granitoids during the Neohimalayan Phase (Early to Middle Miocene). The LHC experienced amphibolite facies metamorphic conditions in the Late Miocene prior to extrusion between the HHC and the very low-grade Lesser Himalayan sediments. In conjunction with climate changes, young tectonic activity in this central part of the Himalayan orogen may have strongly influenced fluvial incision and erosion, and therefore, contributed to the accelerated uplift, as indicated by extensive accumulation of Late Miocene to Early Pleistocene fluviatile-lacustrine sediments in the Zanda basin, the Transhimalayan headwaters of the Sutlej, in Western Tibet.

Angle-specific torque profiles of concentric and eccentric thigh muscle strength 20 years after anterior cruciate ligament injury.

Thigh muscle weakness prevails following anterior cruciate ligament (ACL) injury, as usually evaluated by peak concentric quadriceps strength. Assessment throughout the range of motion (ROM), and for antagonists may provide more comprehensive information. We evaluated angle-specific torque profiles and ratios of isokinetic thigh muscle strength in 70 individuals 23 ± 2 years post-ACL injury (44males, 46.9 ± 5.4 years); 33 treated with ACL-reconstruction (ACL-R), and 37 treated only with physiotherapy (ACL-PT), and 33 controls. Quadriceps and hamstrings torques for concentric/eccentric contractions (90°/s) and ratios between hamstrings/quadriceps strength (HQ) were compared between and within groups using inferential functional data methods. The injured ACL-R leg had lower concentric and eccentric quadriceps strength compared to non-injured leg throughout the ROM, and lower concentric (interval 70-79°) and eccentric (64-67°) quadriceps strength compared to controls. The injured ACL-PT leg showed lower eccentric quadriceps strength (53-77°) than non-injured leg and lower concentric (41-79°) and eccentric (52-81°) quadriceps and eccentric hamstrings (30-77°) strength than controls. There were no group differences for HQ-ratios. The injured ACL-R leg had higher HQ-ratio (34-37°) than non-injured leg. Angle-specific torque profiles revealed strength deficits, masked if using only peak values, and seem valuable for ACL-injury rehabilitation.

Spontaneous isolated midtrimester fracture of tibia and fibula in a normal fetus with in utero healing and good long-term outcome.

We report a case of spontaneous intrauterine fracture of the right tibia and fibula in an otherwise healthy fetus at 20 weeks of gestation. The fracture healed in utero in an abnormal position. Postnatal development of the baby was normal with spontaneous correction of the angulation, and no underlying disease could be discovered. Spontaneous isolated fetal fractures are rare and need to be differentiated from fractures that occur due to trauma or underlying skeletal diseases.

Systemic inflammatory markers in older persons: the effect of oral nutritional supplementation with prebiotics.

OBJECTIVE: To evaluate the effect of oral nutritional supplementation with and without oligosaccharides on gut bacteriology, in particular the bifidogenic flora, and on immunology and inflammatory parameters in older persons at risk of malnutrition. DESIGN: Prospective, randomized, double-blind, controlled study. SETTING: Division of Geriatric Medicine, St. Louis University, Missouri, United States. PARTICIPANTS: Seventy-four community dwelling elderly and/or nursing home subjects (age superior 70 y; 84 +/- 7 years) either undernourished or at risk of undernutrition. INTERVENTION: Daily liquid supplements, with (1.3 g/250 ml) and without oligosaccharides (OS) for 12 weeks. MEASUREMENTS: Nutritional evaluation, serum immunoglobulins, lymphocyte subsets, various cytokines and the endotoxin soluble receptor CD14 (sCD14) in serum, and cytokines specific mRNA in peripheral blood mononuclear cells at baseline and 12 weeks, and fecal bacteriologicy. RESULTS: Specific mRNA extracted from blood leucocytes showed a different level of pro-inflammatory gene activation: TNF-alpha mRNA and IL-6 mRNA diminished in the OS group after 12 weeks, while no changes were detected in the control group (P=0.05 and P=0.04 respectively). Serum levels of sCD14, a product shed by activated macrophages, decreased only in the OS group without reaching statistical significance (P=0.08). No significant differences were detected in the fecal gut flora or in the nutritional parameters. CONCLUSIONS: This study shows that the administration of supplements in older persons at risk of malnutrition may benefit from the addition of prebiotics that can improve the low noise inflammatory process frequently observed in this population.

The Sheep Grimace Scale as an indicator of post-operative distress and pain in laboratory sheep.

The EU Directive 2010/63/EU changed the requirements regarding the use of laboratory animals and raised important issues related to assessing the severity of all procedures undertaken on laboratory animals. However, quantifiable parameters to assess severity are rare, and improved assessment strategies need to be developed. Hence, a Sheep Grimace Scale (SGS) was herein established by observing and interpreting sheep facial expressions as a consequence of pain and distress following unilateral tibia osteotomy. The animals were clinically investigated and scored five days before surgery and at 1, 3, 7, 10, 14 and 17 days afterwards. Additionally, cortisol levels in the saliva of the sheep were determined at the respective time points. For the SGS, video recording was performed, and pictures of the sheep were randomized and scored by blinded observers. Osteotomy in sheep resulted in an increased clinical severity score from days 1 to 17 post-surgery and elevated salivary cortisol levels one day post-surgery. An analysis of facial expressions revealed a significantly increased SGS on the day of surgery until day 3 post-surgery; this elevated level was sustained until day 17. Clinical severity and SGS scores correlated positively with a Pearson´s correlation coefficient of 0.47. Further investigations regarding the applicability of the SGS revealed a high inter-observer reliability with an intraclass correlation coefficient of 0.92 and an accuracy of 68.2%. In conclusion, the SGS represents a valuable approach for severity assessment that may help support and refine a widely used welfare assessment for sheep during experimental procedures, thereby meeting legislation requirements and minimizing the occurrence of unrecognized distress in animal experimentation.

Changes of gut microbiota and immune markers during the complementary feeding period in healthy breast-fed infants.

INTRODUCTION: Little is known about changes in intestinal microbiota during the important period of complementary feeding (weaning). This descriptive study investigated changes of selected gut microbiota and markers of gut permeability and the immune system in breast fed infants during the complementary feeding period. METHODS: 22 healthy, exclusively breast fed infants (from birth to 4 months) with no antibiotic intake during the month prior to the study, were followed from 4 to 9 months of age. Faecal and saliva samples were collected at the start of the study (V0) and at monthly intervals (V1-V5) for measurement of selective gut microbiota (bifidobacteria, lactobacilli, vancomycin-insensitive lactobacilli, enterobacteria, enterococci, Clostridium perfringens) using semi-selective media. Immune markers (alpha-1-antitrypsin, eosinophil cationic protein (ECP), secretory IgA and TNF-alpha were measured in saliva and secretory IgA and TNF-alpha in faecal samples. RESULTS: High stool bifidobacteria counts at the start of the study (7.99 1 1.95 log10 CFU/g faeces) remained stable throughout the 5 months of complementary feeding while counts of enterobacteria and enterococci increased with age (P < 0.05 and P = 0.02 respectively). Vancomycin-insensitive lactobacilli increased significantly during weaning for V0 to V3 (P < 0.01), and then decreased slightly (V4). Faecal Clostridium perfringens remained below the detection limit during the study and parameters measured in saliva did not change. Faecal ECP decreased significantly from 1.011.4 (V0) to 0.510.9 mg/mg protein (V5) P = 0.03. CONCLUSION: Age and/or diet modifications during complementary feeding had no impact on faecal bifidobacteria counts but increased those of enterobacteria and enterococci. Transient increases in faecal lactobacilli and vancomycin-insensitive lactobacilli counts were observed. The reduction in faecal ECP may indicate a decrease in gut permeability (reinforcement of gut mucosa integrity) during the weaning period with age [corrected]

Detection of antibodies against Theiler's murine encephalomyelitis virus GDVII strain in experimental guinea pigs.

A disease affecting guinea pigs called 'guinea pig lameness' characterized by clinical signs of depression, lameness of limbs, flaccid paralysis, weight loss and death within a few weeks was first described by Römer in 1911. After a research group in our facility kept laboratory guinea pigs from two different origins together in one room, lameness was observed in two animals. Further investigations revealed a serological immune response against Theiler's murine encephalomyelitis virus (TMEV; GDVII strain) in these animals. Histopathology of the lumbar spinal cord of these animals showed mononuclear cell infiltration and necrotic neurons in the anterior horn. Therefore, all guinea pigs from this contaminated animal unit, from other units in our facility, as well as from different European institutions and breeding centres were screened for antibodies directed against GDVII. Our investigations showed that approximately 80% of all guinea pigs from the contaminated animal unit were seropositive for GDVII, whereas animals from other separate units were completely negative. In addition, 43% of tested sera from the different European institutions and breeding centres contained antibodies against GDVII. The present data confirm that an unknown viral infection causes an immune response in experimental guinea pigs leading to seroconversion against GDVII and that guinea pigs from a commercial breeder are the source of the infection.

Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn's Disease.

UNLABELLED: Crohn's disease (CD) results from a complex interplay between host genetic factors and endogenous microbial communities. In the current study, we used Ion Torrent sequencing to characterize the gut bacterial microbiota (bacteriome) and fungal community (mycobiome) in patients with CD and their nondiseased first-degree relatives (NCDR) in 9 familial clusters living in northern France-Belgium and in healthy individuals from 4 families living in the same area (non-CD unrelated [NCDU]). Principal component, diversity, and abundance analyses were conducted, and CD-associated inter- and intrakingdom microbial correlations were determined. Significant microbial interactions were identified and validated using single- and mixed-species biofilms. CD and NCDR groups clustered together in the mycobiome but not in the bacteriome. Microbiotas of familial (CD and NCDR) samples were distinct from those of nonfamilial (NCDU) samples. The abundance of Serratia marcescens and Escherichia coli was elevated in CD patients, while that of beneficial bacteria was decreased. The abundance of the fungus Candida tropicalis was significantly higher in CD than in NCDR (P = 0.003) samples and positively correlated with levels of anti-Saccharomyces cerevisiae antibodies (ASCA). The abundance of C. tropicalis was positively correlated with S. marcescens and E. coli, suggesting that these organisms interact in the gut. The mass and thickness of triple-species (C. tropicalis plus S. marcescens plus E. coli) biofilm were significantly greater than those of single- and double-species biofilms. C. tropicalis biofilms comprised blastospores, while double- and triple-species biofilms were enriched in hyphae. S. marcescens used fimbriae to coaggregate or attach with C. tropicalis/E. coli, while E. coli was closely apposed with C. tropicalis Specific interkingdom microbial interactions may be key determinants in CD. IMPORTANCE: Here, we characterized the gut bacterial microbiota (bacteriome) and fungal community (mycobiome) in multiplex families with CD and healthy relatives and defined the microbial interactions leading to dysbiosis in CD. We identified fungal (Candida tropicalis) and bacterial (Serratia marcescens and Escherichia coli) species that are associated with CD dysbiosis. Additionally, we found that the level of anti-Saccharomyces cerevisiae antibodies (ASCA; a known CD biomarker) was associated with the abundance of C. tropicalis We also identified positive interkingdom correlations between C. tropicalis, E. coli, and S. marcescens in CD patients and validated these correlations using in vitro biofilms. These results provide insight into the roles of bacteria and fungi in CD and may lead to the development of novel treatment approaches and diagnostic assays.

Expression of a retinoid-inducible tumor suppressor, Tazarotene-inducible gene-3, is decreased in psoriasis and skin cancer.

Tazarotene-induced gene-3 (TIG-3), isolated from human keratinocytes treated with the retinoic acid receptor-selective retinoid Tazarotene, is homologous to H-rev, a class II tumor suppressor. TIG-3 gene localized to chromosome 11q23, a site of loss of heterozygosity in several malignancies. Retinoids influence epidermal differentiation and are used to treat and prevent skin cancer. Therefore, we studied TIG-3 mRNA expression in psoriasis and in basal and SCCs by in situ hybridization and a quantitative QT-RT-PCR assay. Psoriasis lesions had significantly lower staining (median, 3) than paired normal control skin (median, 4; P = 0.012). TIG-3 mRNA was significantly higher in normal control skin (P = 0.001), in paired adjacent skin (median, 3; P = 0.007), and in overlying epidermis (median, 3.0; P = 0.0001) than in 21 SCC specimens as a group (median, 1.5).

Seated postural neck and trunk reactions to sideways perturbations with or without a cognitive task.

Driving on irregular terrain will expose the driver to sideways mechanical shocks or perturbations that may cause musculoskeletal problems. How a cognitive task, imposed on the driver, affects seated postural reactions during perturbations is unknown. The aim of the present study was to investigate seated postural reactions in the neck and trunk among healthy adults exposed to sideways perturbations with or without a cognitive task. Twenty-three healthy male subjects aged 19-36 years, were seated on a chair mounted on a motion system and randomly exposed to 20 sideways perturbations (at two peak accelerations 5.1 or 13.2m/s(2)) in two conditions: counting backwards or not. Kinematics were recorded for upper body segments using inertial measurement units attached to the body and electromyography (EMG) was recorded for four muscles bilaterally in the neck and trunk. Angular displacements (head, neck, trunk and pelvis) in the frontal plane, and EMG amplitude (normalised to maximum voluntary contractions, MVC) were analysed. The cognitive task provoked significantly larger angular displacements of the head, neck and trunk and significantly increased EMG mean amplitudes in the upper neck during deceleration, although 10% of MVC was never exceeded. A cognitive task seems to affect musculoskeletal reactions when exposed to sideways perturbations in a seated position.

Detection of Rochalimaea henselae DNA by polymerase chain reaction from suppurative nodes of children with cat-scratch disease.

A polymerase chain reaction (PCR) assay was designed to amplify DNA from Rochalimaea henselae, Rochalimaea quintana and Afipia felis in the purulent material from lymph nodes in three patients with clinical cat-scratch disease (CSD) and two patients with lymphadenitis from other causes. All of the patients with CSD had positive immunofluorescent antibody serology for R. henselae, while none of the controls was positive. PCR amplification confirmed the presence of R. henselae DNA and the absence of R. quintana and A. felis DNA in the purulent material from CSD patients. PCR samples from control patients were negative. The PCR amplification of R. henselae DNA was performed quickly and with great sensitivity and specificity. It confirmed the presence of R. henselae in the CSD patients and eliminated the need for more extensive diagnostic and therapeutic procedures.

Booster response to acellular pertussis vaccine in children primed with acellular or whole cell vaccines.

Few data are available on the effect of a booster dose of acellular pertussis vaccine in children primed as infants with acellular vaccine. We administered acellular pertussis vaccine (ACV) at 19 months to children immunized in infancy with ACV or whole cell vaccine. Forty-one infants had been randomly assigned to receive either ACV or whole cell vaccine at 2, 4 and 6 months of age. Antibody titers to pertussis toxin and filamentous hemagglutinin were significantly higher in ACV than whole cell vaccine recipients at 7 months; at 15 months antibody to filamentous hemagglutinin (but not pertussis toxin) remained significantly higher among those receiving ACV. At 19 months all 41 children received an ACV booster. Local and systemic reactions were few and minor and were equally distributed between the two groups. All children responded to booster with significant increases in antibody; these increases tended to be greater for those having been primed with ACV. ACV booster immunization appears safe and immunogenic, regardless of the vaccine given for primary immunization.

An antimelanoma-barley ribosome inactivating protein conjugate is cytotoxic to melanoma cells in vitro.

The ribosome inactivating protein (BRIP) from barley is a single polypeptide chain (Mr = 32,000 Dalton) and is nontoxic to intact cells. The BRIP has been purified to homogeneity by modifications of the methods of Roberts and Selitrennikoff and crosslinked to monoclonal antibodies by Succinimidyl-3 (2- Pyridyldithio) -Propionate (SPDP) and by the cystamine-EDAC methods. The resulting hybrids were purified from the free BRIP by gel filtration on a Sephadex G-75 column. The model suicide transport agents were assayed against melanoma cells; K-562 cells were used as control. The hybrids were found to be selectively toxic to melanoma cells in a dose dependent manner.