Phylosymbiosis and metabolomics resolve phenotypically plastic and cryptic sponge species in the genus Agelas across the Caribbean basin.

Fundamental to holobiont biology is recognising how variation in microbial composition and function relates to host phenotypic variation. Sponges often exhibit considerable phenotypic plasticity and also harbour dense microbial communities that function to protect and nourish hosts. One of the most prominent sponge genera on Caribbean coral reefs is Agelas. Using a comprehensive set of morphological (growth form, spicule), chemical and molecular data on 13 recognised species of Agelas in the Caribbean basin, we were able to define only five species (=clades) and found that many morphospecies designations were incongruent with phylogenomic and population genetic analyses. Microbial communities were also strongly differentiated between phylogenetic species, showing little evidence of cryptic divergence and relatively low correlation with morphospecies assignment. Metagenomic analyses also showed strong correspondence to phylogenetic species, and to a lesser extent, geographical and morphological characters. Surprisingly, the variation in secondary metabolites produced by sponge holobionts was explained by geography and morphospecies assignment, in addition to phylogenetic species, and covaried significantly with a subset of microbial symbionts. Spicule characteristics were highly plastic, under greater impact from geographical location than phylogeny. Our results suggest that while phenotypic plasticity is rampant in Agelas, morphological differences within phylogenetic species affect functionally important ecological traits, including the composition of the symbiotic microbial communities and metabolomic profiles.

Medical infrared thermal imaging of canine appendicular bone neoplasia.

BACKGROUND: Medical infrared thermal imaging (MITI) is a noninvasive imaging modality used in veterinary medicine as a screening tool for musculoskeletal and neurological disease processes. An infrared camera measures the surface body heat and produces a color map that represents the heat distribution. Local trauma or disease can impair the autonomic nervous system, which leads to changes in the local dermal microcirculation and subsequent alteration of surface body heat. Disruption of autonomic flow to the cutaneous vasculature at deeper levels can also result in asymmetric thermographic results. The purpose of this study was to evaluate surface temperature differences between limbs affected by bone neoplasia and their normal contralateral limbs. RESULTS: A statistically significant difference in average temperature was noted between regions of interest of the two groups (paired difference: 0.53 C° ± 0.14; P = 0.0005). In addition, pattern recognition analysis yielded a 75-100% success rate in lesion identification. CONCLUSIONS: Significant alterations noted with average temperature and thermographic patterns indicate that MITI can document discernible changes associated with the presence of canine appendicular bone tumors. While MITI cannot be used as the sole diagnostic tool for bone cancer, it can be used as a screening modality and may be applicable in early detection of cancer.

Pathogenic tau species drive a psychosis-like phenotype in a mouse model of Alzheimer's disease.

Psychotic Alzheimer's disease (AD+P) is a rapidly progressive variant of AD associated with an increased burden of frontal tau pathology that affects up to 50% of those with AD, and is observed more commonly in females. To date, there are no safe and effective medication interventions with an indication for treatment in this condition, and there has been only very limited exploration of potential animal models for pre-clinical drug development. Pathogenic tau is over represented in the frontal cortex in AD+P, especially in females. In order to develop a candidate animal model of AD+P, we employed a tau mouse model with a heavy burden of frontal tau pathology, the rTg(tauP301L)4510 mouse, hereafter termed rTg4510. We explored deficits of prepulse inhibition of acoustic startle (PPI), a model of psychosis in rodents, and the correlation between pathogenic phospho-tau species associated with AD+P and PPI deficits in female mice. We found that female rTg4510 mice exhibit increasing PPI deficits relative to littermate controls from 4.5 to 5.5 months of age, and that these deficits are driven by insoluble fractions of the phospho-tau species pSer396/404, pSer202, and pThr231 found to be associated with human AD+P. This preliminary data suggests the utility of the rTg4510 mouse as a candidate disease model of human female AD+P. Further work expanded to include both genders and other behavioral outcome measures relevant to AD+P is necessary.

[Ultrasonographic finding and treatment of a cow with pyelonephrosis]. / Sonographische Befunde und Therapie bei einer Kuh mit Pyonephrose.

Ultrasonography of a six-year-old Simmental cow revealed an abscess like structure, approximately 15 cm in diameter, in place of the right kidney. The cow had a history of colic for 4 days and was referred to our clinic with a tentative diagnosis of caecal dilatation. The cow voided dark opaque urine with white floccules. Laboratory examination yielded increased haematocrit, leukocytosis with left shift, hyperbilirubinaemia and azotaemia. The diagnosis was confirmed, the caecum emptied surgically and the pus-filled structure at the site of the right kidney removed. A diagnosis of pyonephrosis was made after pathological examination of the pus-filled structure.

Malignant peripheral nerve sheath tumour in the nasopharynx of a cow.

This case describes the findings in a Swiss Braunvieh cow with a malignant peripheral nerve sheath tumour (MPNST) in the nasopharynx. The major clinical signs were mixed dyspnoea with inspiratory and expiratory noises. Radiographic views of the head revealed an irregular mass with soft-tissue density in the nasopharynx originating from the dorsal pharynx and occupying and restricting the pharyngeal cavity. Endoscopic examination showed a lobulated mass obstructing almost the entire lumen of the aboral nasal passages and nasopharynx. Postmortem examination revealed a lobulated mass in the choanae with a broad attachment to the dorsal pharynx and histologically a soft tissue sarcoma with tumour cells positive for the S-100 and p75NTR (neurotrophin receptor) proteins and negative for CNPase. Electron microscopic examination showed few structures that indicated that the tumour originated from Schwann cells.

Fluorescent epibiotic microbial community on the carapace of a Bahamian ostracod.

Ostracods collected from shallow coral reefs in the Bahamas were found to exhibit blue light-stimulated orange fluorescence at night. Fluorescent spectra revealed the presence of orange fluorescence with a maximum emission at ~595 nm on the carapace of these ostracods, while scanning electron microscopy revealed a morphologically diverse microbial community covering the entire carapace of these ostracods. Pyrosequencing and cyanobacterial-specific 16S rRNA sequencing reveals that this epibiont community is highly diverse and highly variable between individual ostracods. Many species of Cyanobacteria in the orders Oscillatoriales and Chroococcales, as well as other Proteobacteria and diatom chloroplast sequences, were identified using the cyanobacterial-specific primers. While no fluorescent proteins or phycoerythrin were detected in these ostracods, it is possible that the observed orange fluorescence is the result of carotenoid fluorescence from Cyanobacteria. The microbial consortium forms an epibiotic biofilm on the carapace of these ostracods whose functions are unknown.

Development of genetic diversity, differentiation and structure over 500 years in four ponderosa pine populations.

Population history plays an important role in shaping contemporary levels of genetic variation and geographic structure. This is especially true in small, isolated range-margin populations, where effects of inbreeding, genetic drift and gene flow may be more pronounced than in large continuous populations. Effects of landscape fragmentation and isolation distance may have implications for persistence of range-margin populations if they are demographic sinks. We studied four small, disjunct populations of ponderosa pine over a 500-year period. We coupled demographic data obtained through dendroecological methods with microsatellite data to discern how and when contemporary levels of allelic diversity, among and within-population levels of differentiation, and geographic structure, arose. Alleles accumulated rapidly following initial colonization, demonstrating proportionally high levels of gene flow into the populations. At population sizes of approximately 100 individuals, allele accumulation saturated. Levels of genetic differentiation among populations (F(ST) and Jost's D(est)) and diversity within populations (F(IS)) remained stable through time. There was no evidence of geographic genetic structure at any time in the populations' history. Proportionally, high gene flow in the early stages of population growth resulted in rapid accumulation of alleles and quickly created relatively homogenous genetic patterns among populations. Our study demonstrates that contemporary levels of genetic diversity were formed quickly and early in population development. How contemporary genetic diversity accumulates over time is a key facet of understanding population growth and development. This is especially relevant given the extent and speed at which species ranges are predicted to shift in the coming century.

[First cases of besnoitiosis in cattle in Switzerland]. / Erste Fälle von Besnoitiose bei Rindern in der Schweiz.

Bovine besnoitiosis has been diagnosed in neighboring countries but not in Switzerland so far. This disease occurs endemically in France and focal outbreaks have been reported in Germany and Italy. To determine if Besnoitia besnoiti is introduced into Switzerland through the import of breeding cattle from France, a systematic serological survey was performed. A total of 412 breeding cattle (from 114 farms) imported from France into Switzerland between 2005 and 2011, were serologically examined for antibodies against B. besnoiti using a commercial ELISA kit (PrioCHECK© Besnoitia Ab 2.0, Prionics AG, Zurich, Switzerland). Sixty-four (15.5 %) animals reacted positive in ELISA. The serologic diagnosis was confirmed by an indirect immunfluorescence test (IFAT) and a Western blot (WB) in only 2 Limousin cows imported from France on a farm in Eastern Switzerland. Subsequently, this whole herd (n = 16) was examined clinically and serologically and 2 additional Limousin cows imported from Germany also reacted positive in the three serological tests. One of these cows presented B. besnoiti tissue cysts in the scleral conjunctiva and typical skin lesions in the head region. The infection was further confirmed cytologically, histopathologically and by PCR. It can be concluded that the parasite is most likely being introduced into Switzerland through the import of infected animals.

A pilot study of activity-based therapy in the arm motor recovery post stroke: a randomized controlled trial.

OBJECTIVE: To determine the efficacy of activity-based therapies using arm ergometer or robotic or group occupational therapy for motor recovery of the paretic arm in patients with an acute stroke (< or =4 weeks) admitted to an inpatient rehabilitation facility, and to obtain information to plan a large randomized controlled trial. DESIGN: Prospective, randomized controlled study. SETTING: Stroke unit in a rehabilitation hospital. SUBJECTS: Thirty patients with an acute stroke (< or =4 weeks) who had arm weakness (Medical Research Council grade 2 or less at the shoulder joint). INTERVENTION: Occupational therapy (OT) group (control) (n = 10), arm ergometer (n = 10) or robotic (n = 10) therapy group. All patients received standard, inpatient, post-stroke rehabilitation training for 3 hours a day, plus 12 additional 40-minute sessions of the activity-based therapy. MAIN MEASURES: The primary outcome measures were discharge scores in the Fugl-Meyer Assessment Scale for upper limb impairment, Motor Status Scale, total Functional Independence Measure (FIM) and FIM-motor and FIM-cognition subscores. RESULTS: The three groups (OT group versus arm ergometer versus robotic) were comparable on clinical demographic measures except the robotic group was significantly older and there were more haemorrhagic stroke patients in the arm ergometer group. After adjusting for age, stroke type and outcome measures at baseline, a similar degree of improvement in the discharge scores was found in all of the primary outcome measures. CONCLUSION: This study suggests that activity-based therapies using an arm ergometer or robot when used over shortened training periods have the same effect as OT group therapy in decreasing impairment and improving disability in the paretic arm of severely affected stroke patients in the subacute phase.

Intensive nutritional supplements can improve outcomes in stroke rehabilitation.

OBJECTIVE: Poor nutrition is a common complication of strokes severe enough to require inpatient rehabilitation. We therefore tested whether intensive nutritional supplements given to undernourished patients from the time of their admission to a specialized stroke rehabilitation service would improve patient outcomes. METHODS: Randomized, prospective, double-blind, single center study comparing intensive nutritional supplementation to routine nutritional supplementation in 116 undernourished patients admitted to a stroke service. The analysis included the 90% of patients who were not lost to follow-up due to acute or subacute hospitalization (n = 102; 51 in each group). The nutritional supplements are commercially available and Food and Drug Administration approved. The primary outcome variable was change in total score on the Functional Independence Measure (FIM). The secondary outcome measurements included the FIM motor and cognitive subscores, length of stay (taken from day of admission), 2-minute and 6-minute timed walk tests measured at admission and on discharge, and discharge disposition (home/not home). RESULTS: Patients receiving intensive nutritional supplementation improved more than those on standard nutritional supplements on measures of motor function (total FIM, FIM motor subscore, 2-minute and 6-minute timed walk tests, all significant at p < 0.002). They did not, however, improve on measures of cognition (FIM cognition score). A higher proportion of patients who received the intensive nutritional supplementation went home compared to those on standard supplementation (p = 0.05). CONCLUSION: Intensive nutritional supplementation, using readily available commercial preparations, improves motor recovery in previously undernourished patients receiving intensive in-patient rehabilitation after stroke.

Molecular mechanisms of action and prediction of response to oxaliplatin in colorectal cancer cells.

The platinum compound oxaliplatin has been shown to be an effective chemotherapeutic agent for the treatment of colorectal cancer. In this study, we investigate the molecular mechanisms of action of oxaliplatin to identify means of predicting response to this agent. Exposure of colon cancer cells to oxaliplatin resulted in G2/M arrest and apoptosis. Immunofluorescent staining demonstrated that the apoptotic cascade initiated by oxaliplatin is characterised by translocation of Bax to the mitochondria and cytochrome c release into the cytosol. Oxaliplatin treatment resulted in caspase 3 activation and oxaliplatin-induced apoptosis was abrogated by inhibition of caspase activity with z-VAD-fmk, but was independent of Fas/FasL association. Targeted inactivation of Bax or p53 in HCT116 cells resulted in significantly increased resistance to oxaliplatin. However, the mutational status of p53 was unable to predict response to oxaliplatin in a panel of 30 different colorectal cancer cell lines. In contrast, the expression profile of these 30 cell lines, assessed using a 9216-sequence cDNA microarray, successfully predicted the apoptotic response to oxaliplatin. A leave-one-out cross-validation approach was used to demonstrate a significant correlation between experimentally observed and expression profile predicted apoptosis in response to clinically achievable doses of oxaliplatin (R=0.53; P=0.002). In addition, these microarray experiments identified several genes involved in control of apoptosis and DNA damage repair that were significantly correlated with response to oxaliplatin.

Neutrophil and monocyte adhesion molecules in bronchopulmonary dysplasia, and effects of corticosteroids.

AIMS: To study a longitudinal change in the expression of adhesion molecules CD11b, CD18, and CD62L on neutrophils and monocytes in very low birth weight babies who develop respiratory distress syndrome, to compare these levels between bronchopulmonary dysplasia (BPD) and non-BPD infants, and to assess the effect of corticosteroid treatment on these adhesion molecules. METHODS: Of 40 eligible neonates, 11 neonates were oxygen dependent at 36 weeks (BPD 36 weeks), 16 infants were oxygen dependent at 28 days, but not at 36 weeks (BPD d28), and 13 infants did not develop BPD. Seventeen neonates received a six day course of steroid treatment. Expression of CD11b, CD18, and CD62L was measured on neutrophils and monocytes in arterial blood on days 1, 3, 7, 14, 21, and 28, and before and 2-3 days after initiation of dexamethasone treatment by flow cytometry. RESULTS: CD18 expression on neutrophils and monocytes and CD62L on neutrophils, measured as mean fluorescent intensity, was significantly decreased in BPD neonates compared to non-BPD neonates on days 1-28. Dexamethasone treatment significantly decreased CD11b, CD18, and CD62L expression on neutrophils, and CD11b and CD18L expression on monocytes. CONCLUSIONS: Decreased CD18 expression on neutrophils and monocytes, and decreased CD62L expression on neutrophils, measured as mean fluorescent intensity during the first four weeks of life in micropremies may be risk factors and early predictors of BPD. Dexamethasone use was associated with decreased expression of CD11b, CD18, and CD62L.

Comparison of 1-micro g and 250-micro g corticotropin stimulation tests for the evaluation of adrenal function in patients with acquired immunodeficiency syndrome.

Many patients with acquired immunodeficiency syndrome (AIDS) have symptoms suggestive of adrenal insufficiency, but a normal 250- micro g corticotropin (ACTH) stimulation test. We compared the results of 1- micro g and standard 250- micro g ACTH stimulation tests in patients with AIDS. Each patient was studied on 2 separate days. On day 1, 1 micro g ACTH was given intravenously at 8 am after an overnight fast and serum cortisol levels were measured at baseline, and 30 and 60 minutes after ACTH infusion. On day 2, the procedure was repeated with 250- micro g ACTH. An absolute peak cortisol value of > 18 micro g/dL and an increment of 7 micro g/dL or more from baseline constituted a normal response. Among 31 patients, 16 (52%) had discrepant results: 14 (45%) had subnormal responses to 1 micro g ACTH but normal responses to 250 micro g ACTH (group 1); 2 (6%) had normal responses to 1 micro g but subnormal responses to 250 micro g (group 2) ACTH; 6 patients (19%) had concordant abnormal responses (group 3); and 9 (30%) had concordant normal responses (group 4). Eight patients of group 1 underwent a confirmatory insulin tolerance test (ITT); 4 of these patients had abnormal responses to ITT. Kappa statistic and McNemar's test were used to evaluate the data. A kappa statistic value of 0.095 and a P value less than.003 for the McNemar test indicate only random level of agreement and significant differences in the probability of positive result between the 2 ACTH tests. We conclude that discrepancies between the 1- micro g and the 250- micro g ACTH stimulation tests are common in patients with AIDS, with the likelihood of agreement with the "gold standard" ITT of only 50% for each test in our sample of patients. Larger studies are needed to further evaluate the use of these tests in patients with AIDS.

Assessment of a bronchoscopy simulator.

The study objective was to validate a flexible bronchoscopy simulator by determining if it could differentiate between expert and novice bronchoscopists. A subsequent evaluation phase was then done to determine whether use of the simulator would improve the rate of bronchoscopy skill acquisition for new pulmonary fellows. A multicenter prospective cohort study was performed using a bronchoscopy simulator. Three cohorts were evaluated based on the number of bronchoscopies previously performed: "experts" (> 500, n = 9), "intermediates" (25 to 500, n = 8), and "novices" (none, n = 11). Each participant performed two simulated cases with performance measures being recorded by the simulator. Performance measures that distinguished between groups were then used to evaluate the learning curve for new fellows training on the simulator. A randomized-controlled trial was then conducted comparing the quality of bronchoscopy performance for new pulmonary fellows who were trained either with conventional methods or with the simulator. Expert bronchoscopists performed better on the simulator than intermediates who performed better than novices in terms of procedure time, percentage of segments visualized, time in red-out, and wall collisions. Training of new fellows demonstrated that after performing 20 bronchoscopic simulations, the skill level acquired with the simulator significantly improved in terms of speed, percentage of segments visualized, time in red-out, and collisions. Fellows trained on the simulator performed better than fellows trained using conventional methods during their first actual bronchoscopies as assessed by procedure time (815 versus 1,168 s, p = 0.001), a bronchoscopy nurse's subjective quality assessment score (7.7 +/- 0.3 versus 3.7 +/- 2.5, p = 0.05), and by a quantitative bronchoscopy quality score (percentage of segments correctly identified/procedure time, 0.119 +/- 0.015 versus 0.046 +/- 034, p = 0.03). In conclusion, the bronchoscopy simulator was able to accurately assess bronchoscopy experience level. Training new fellows on the bronchoscopy simulator leads to more rapid acquisition of bronchoscopy expertise compared with conventional training methods. This technology has the potential to facilitate bronchoscopy training and to improve objective evaluations of bronchoscopy skills.

Exposure to ultraviolet radiation (290-400 nm) causes oxidative stress, DNA damage, and expression of p53/p73 in laboratory experiments on embryos of the spotted salamander, Ambystoma maculatum.

Developing embryos of the spotted salamander, Ambystoma maculatum, exposed to ultraviolet radiation (UVR; 290-400 nm) in the laboratory show a significant sensitivity to UVB (290-320 nm) radiation. Embryos in laboratory experiments exhibited significant DNA damage during exposures to UVR despite a significant increase in the production of the protective pigment melanin in response to UVR exposure. DNA damage occurs as a result of both the direct effects of exposure to UVR, and the indirect effects are mediated by the production of reduced oxygen intermediates. The production of reactive oxygen species initiates the expression of p53/p73 that leads to either DNA repair or apoptosis. When similar experiments are conducted on salamander embryos exposed to solar UVR in vernal pools, the embryos show significantly less sensitivity and higher survivorship. The differences between laboratory and field experiments are a result of the attenuation of UVR caused by the accumulation of dissolved organic carbon within the pools of these wooded areas. These findings suggest that northeastern populations of spotted salamanders are sensitive to UVR but are not significantly affected by present-day irradiances of UVR in the field. These results do suggest that continued decreases in stratospheric ozone over temperate latitudes have the potential to affect spotted salamanders in their natural habitats.

Immunophenotypic analysis of HIV-infected children: alterations within the first year of life, changes with disease progression, and longitudinal analyses of lymphocyte subsets.

Perinatal infection with human immunodeficiency virus (HIV) results in tremendous activation of the pediatric immune system. An important component of understanding the pathogenesis of this disease is to characterize and quantify antigenic indicators of activation within the peripheral lymphocyte population. We measured T-lymphocyte activation and maturation antigens in a cohort of 112 HIV-infected children treated with antiretroviral therapy according to the current standard of care. Changes in expression of CD95, HLA-DR, and CD45RO were evident in 22 HIV-infected children younger than 1 year of age. A comparison of phenotypic profiles of children in mild, moderate, and severe immune categories revealed perturbations of CD28, CD38, CD45RA, CD45RO, CD95, and HLA-DR. Finally, a novel analysis of 56 HIV-infected children based on the repeated collection of data over time (median of seven observations over 33 months) demonstrated a strong negative correlation between the percentage CD4 and the percentage of CD45RO, CD95, and HLA-DR on both CD4 and CD8 cells. Our data implicate persistent immune activation, beginning within the first year of life, as a major driving force in the pathogenesis of perinatally acquired HIV disease.

Comparison of the auditory and visual privacy of emergency department treatment areas with curtains versus those with solid walls.

STUDY OBJECTIVE: The design and function of emergency departments may allow breaches of privacy that could adversely affect patient satisfaction and medical care. We sought to determine whether patients perceive less privacy in ED treatment areas with curtains than in rooms with solid walls. METHODS: Patients 18 years and older at a university hospital ED who received care in a room with solid walls and a door, a curtained area next to the nurses' station, or a curtained area away from the nurses' station were surveyed. Patients responded on a 5-point Likert scale to 11 questions regarding privacy. Differences between areas were determined by using the Kruskal-Wallis and Mann-Whitney tests and were considered significant at P values of less than.05. RESULTS: Structured interviews were conducted with 108 ED patients. Responses from those in the curtained areas were similar. Compared with those in the rooms with walls, these patients more often believed that they could overhear others and that others could hear them, view them, hear personal information, and view personal parts of their bodies (P < or =.04 for all). They also perceived a lower overall sense of privacy (P <.01). Of all those surveyed, 85.2% reported "a lot of" or "complete" respect for privacy by the staff, and 92.6% experienced at least as much privacy as they expected, with no difference between areas. CONCLUSION: Patients perceive significantly less auditory and visual privacy in ED treatment areas with curtains compared with a room with solid walls. Consideration of these findings in current practice and in future ED design and construction is suggested.

An open-label study of the treatment efficacy of olanzapine for Tourette's disorder.

BACKGROUND: An open-label trial was performed to explore efficacy and safety of olanzapine, an atypical neuroleptic with diverse receptor activity including both dopamine-2 and serotonin-2A and -2C antagonism, for treatment of Tourette's disorder. METHOD: Ten adult patients aged 20 to 44 years with Tourette's disorder were treated using an open-label, flexible dosing schedule for 8 weeks. Three patients who continued olanzapine were reevaluated after 6 months. Three subjects were psychotropic medication naive, 5 patients experienced intolerable side effects with conventional neuroleptics, and 2 patients had remote (> or = 10 years) successful response to conventional neuroleptics. Tic severity was rated by the Yale Global Tic Severity Scale; weight, vital signs, and adverse effects were assessed weekly. Electrocardiogram, laboratory studies, and comorbid symptoms, assessed by the Yale-Brown Obsessive Compulsive Scale and ADHD Behavior Checklist for Adults, were measured at baseline and at week 8. RESULTS: Two of 10 patients prematurely discontinued olanzapine owing to excessive sedation. Of 8 patients who completed the 8-week trial, 4 (50%) demonstrated reduction of global tic severity scores by > or = 20 points, and 6 (75%) demonstrated reductions by > or = 10 points. No significant changes in comorbid symptoms were demonstrated. Sedation, weight gain, increased appetite, dry mouth, and transient asymptomatic hypoglycemia were the most common side effects. Tic improvements were maintained in 3 patients reassessed 6 months later. Final olanzapine dosages ranged from 2.5 mg to 20 mg daily (mean = 10.9 mg/day). CONCLUSION: This open-label study suggests that olanzapine should be explored as a potential alternative to conventional neuroleptic medications for treatment of motor tics and Tourette's disorder.

Expression of homologues for p53 and p73 in the softshell clam (Mya arenaria), a naturally-occurring model for human cancer.

Homologues for human p53 (Hsp53) and p73 (Hsp73) genes were cloned and expression patterns for their corresponding proteins analysed in tissues from normal and leukemic softshell clams (Mya arenaria). These are the first structural and functional data for p53 and p73 cDNAs and gene products in a naturally occurring, non-mammalian disease model. Core sequence of the predicted clam p53 (Map53) and p73 (Map73) proteins is virtually identical and includes the following highly conserved regions: the transcriptional activation domain (TAD), MDM2 binding site, ATM phosphorylation site, proline rich domain, DNA binding domains (DBDs) II-V, nuclear import and export signals and the tetramerization domain. The core sequence is a structural mosaic of the corresponding human proteins, with the TAD and DBDs resembling Hsp53 and Hsp73, respectively. This suggests that Map53 and Map73 proteins may function similarly to human proteins. Clam proteins have either a short (Map53) or long (Map73) C-terminal extension. These features suggest that Map53 and Map73 may be alternate splice variants of a p63/p73-like ancestral gene. Map73 is significantly upregulated in hemocytes and adductor muscle from leukemic clams. In leukemic hemocytes, both proteins are absent from the nucleus and sequestered in the cytoplasm. This observation suggests that a non-mutational p53/p73-dependent mechanism may be involved in the clam disease. Further studies of these gene products in clams may reveal p53/p73-related molecular mechanisms that are held in common with Burkitt's lymphoma or other human cancers.

A dose of 75 microg/kg/d of i.v. anti-D increases the platelet count more rapidly and for a longer period of time than 50 microg/kg/d in adults with immune thrombocytopenic purpura.

Treatment with 75 microg/kg/d intravenous (i.v.) anti-D was compared with 50 microg/kg/d in a prospective randomized study of 27 RhD-positive, human immunodeficiency virus-negative, adult, acute, non-splenectomized patients with immune thrombocytopenic purpura (ITP) and platelet counts < or = 30 x 109/l. The higher dose resulted in greater median d 1 (43 x 109/l vs. 7.5 x 109/l; P = 0.012) and d 7 (153 x 109/l vs. 64.5 x 109/l; P = 0.001) platelet increases despite no greater haemoglobin decrease. Children with acute ITP receiving 75 microg/kg/d had overnight platelet increases in seven out of nine cases. The duration of effect at the 75 microg/kg/d dose was 46 d vs. 21 d (P = 0.03). Adverse events were mild to moderate and ameliorated with prednisone and acetaminophen premedication.