“We have shown before that 2-week intrastriatal L-3,4-dihy


“We have shown before that 2-week intrastriatal L-3,4-dihydroxyphenylalanine (L-dopa)

infusion significantly decreased contralateral rotations induced by acute intraperitoneal L-dopa/carbidopa and increased striatal tryptophan hydroxylase in 6-hydroxydopamine-lesioned rats. Here, we examined the effect of acutely administered L-dopa (10 mu g) into 6-hydroxydopamine-lesioned rat striata under Hedgehog antagonist the inhibition of tryptophan hydroxylase by 4-chloro-DL-phenylalanine. Acute intrastriatal L-dopa infusion significantly decreased contralateral rotations induced by intraperitoneal L-dopa/carbidopa (10/30 mg/kg) 1 and 7 days after intrastriatal L-dopa. This desensitization to L-dopa occurred only when there was a striatal 5-hydroxytryptamine (5-HT) imbalance, not when 5-HT levels in the intact and lesioned sides were similar, either very low (day 1 postinfusion) or similarly recovered (day 7 postinfusion). We conclude that 5-HT plays a significant role in the striatal dopaminergic imbalance that evokes the rotational behavior. NeuroReport 20:313-318 (C) 2009 Wolters Kluwer Health vertical bar Lippincott

Williams & Wilkins.”
“CASE PRESENTATION

A 30-year-old Caucasian male on chronic hemodialysis presents with a 4-day history of right flank pain accompanied by fever, nausea, and anorexia.

On physical examination, he had a heart selleck inhibitor rate of 100 beats per minute and a blood pressure of 147/95mmHg. The abdomen was soft. There was no tenderness or guarding over the allograft, and lymph nodes were not enlarged. His remaining examination was unremarkable.

sBlood and urine cultures were negative. The patient had undergone ultrasonographic examination of the allograft every year since 1998 with evidence of

simple cysts in the parenchyma (Figure 1a) and a persistent fluid collection adjacent to the lower pole representing a lymphocele. A CT scan of the abdomen showed two sub-centimeter low-density lesions within the enlarged right transplanted kidney, suspicious for an infectious or neoplastic process. A persistent and stable right lower quadrant lymphocele was also present. Aspiration of the lymphocele yielded sterile fluid without evidence of infection. A transplant nephrectomy was performed.”
“The effects of negative Vitamin B12 emotional intensity on memory-related brain activity were tested by using human scalp event-related potentials (ERP). A neural index of memory function – the electrophysiological ‘Old-New’ effect – was obtained from participants undertaking a memory recognition test of previously studied (‘old’) and unstudied (‘new’) pictures of variable levels of negative emotional intensity. The magnitude of the old-new effect was compared across four different levels of linearly increasing stimulus emotional intensity. Results revealed an inverted-U-shaped effect of emotional intensity on the magnitude of ERP old-new differences starting at 300 ms after stimulus onset.

By means of in vivo fate mapping, we found a striking variability

By means of in vivo fate mapping, we found a striking variability of immune responses derived from individual CD8(+) T cells and show that robust acute and recall immunity requires the initial recruitment of multiple precursors. Unbiased mathematical modeling identifies the random integration of multiple differentiation and division events as the driving force behind this variability. Within this probabilistic framework, cell fate is specified along a linear developmental path that progresses from slowly proliferating long-lived to rapidly expanding short-lived subsets. These data provide insights into how complex biological systems implement stochastic processes to

guarantee robust outcomes.”
“Upon infection, antigen-specific CD8(+) T lymphocyte responses display a highly reproducible pattern of expansion and contraction that is thought to reflect a uniform behavior of individual Niraparib mouse cells. We tracked the progeny

of individual mouse CD8(+) T cells Citarinostat manufacturer by in vivo lineage tracing and demonstrated that, even for T cells bearing identical T cell receptors, both clonal expansion and differentiation patterns are heterogeneous. As a consequence, individual naive T lymphocytes contributed differentially to short-and long-term protection, as revealed by participation of their progeny during primary versus recall infections. The discordance in fate of individual naive T cells argues against asymmetric division as a singular driver of CD8(+) T cell heterogeneity and demonstrates that reproducibility of CD8(+) T cell responses is achieved through population averaging.”
“Visual imagery during sleep has long been a topic diglyceride of persistent speculation, but its private nature has hampered objective analysis. Here we present a neural decoding approach in which machine-learning models predict

the contents of visual imagery during the sleep-onset period, given measured brain activity, by discovering links between human functional magnetic resonance imaging patterns and verbal reports with the assistance of lexical and image databases. Decoding models trained on stimulus-induced brain activity in visual cortical areas showed accurate classification, detection, and identification of contents. Our findings demonstrate that specific visual experience during sleep is represented by brain activity patterns shared by stimulus perception, providing a means to uncover subjective contents of dreaming using objective neural measurement.”
“Background: HIV evolves rapidly at the epidemiological level but also at the within-host level. The virus’ within-host evolutionary rates have been argued to be much higher than its between-host evolutionary rates. However, this conclusion relies on analyses of a short portion of the virus envelope gene.

In mutant mice lacking NE, induction of Fos was normal in all reg

In mutant mice lacking NE, induction of Fos was normal in all regions of the hippocampus and amygdala shortly after fear conditioning. In contrast, when testing contextual fear 1 day after framing, induction of Fos in CA1 and the central nucleus of the amygdala (CeA), but not CA3, the dentate gyrus or other amygdaloid nuclei, was impaired in the mutant mice. This pattern corresponded to the memory retrieval deficit exhibited by these mice. On the other hand, induction was normal in CA1 and CeA when testing cued

fear 1 day after training, or contextual fear 1 week or 1 month after training, conditions in which retrieval are normal in the absence of NE. Acute restoration of NE in the mutant mice before testing but not before training rescued retrieval of contextual fear and restored Fos induction in CA1 and CeA. Nec-1s solubility dmso Because NE facilitates retrieval through the activation of beta(1)-adrenergic receptors, beta(1) knockout mice were also examined and found to exhibit reduced induction of Fos in CA1 and CeA following retrieval. Based on these and previous results, we hypothesize that adrenergic signaling is critical for the full activation of CA1 pyramidal neurons in response to excitatory input from CA3 pyramidal neurons conveying retrieved contextual information. selleck inhibitor (C) 2011 IBRO. Published

by Elsevier Ltd. All rights reserved.”
“Drug resistance is a growing concern with clinical use of tyrosine kinase inhibitors. Utilizing in vitro models of intrinsic drug resistance and stromal-mediated chemoresistance, as well as functional mouse models of progressive and residual disease, we attempted to develop a potential therapeutic approach designed to suppress leukemia recurrence following treatment with selective

Inulin kinase inhibitors. The novel inhibitor of apoptosis (IAP), LCL161, was observed to potentiate the effects of tyrosine kinase inhibition against leukemic disease both in the absence and presence of a stromal protected environment. LCL161 enhanced the proapoptotic effects of nilotinib and PKC412, against leukemic disease in vitro and potentiated the activity of both kinase inhibitors against leukemic disease in vivo. In addition, LCL161 synergized in vivo with nilotinib to reduce leukemia burden significantly below the baseline level suppression exhibited by a moderate-to-high dose of nilotinib. Finally, LCL161 displayed antiproliferative effects against cells characterized by intrinsic resistance to tyrosine kinase inhibitors as a result of expression of point mutations in the protein targets of drug inhibition. These results support the idea of using IAP inhibitors in conjunction with targeted tyrosine kinase inhibition to override drug resistance and suppress or eradicate residual disease. Leukemia (2010) 24, 2100-2109; doi:10.1038/leu.2010.

In both cases, the sensitivity to picrotin was essentially unalte

In both cases, the sensitivity to picrotin was essentially unaltered. The results indicated that alpha 2 subunits can determine the picrotin sensitivity of alpha check details 1 alpha 2-heteromeric receptors and that direct gating of the alpha 2 subunit is not required for this picrotin inhibition. NeuroReport 23:1017-1020 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Dopamine D-2 receptors are the main target of antipsychotic drugs. In the brain, D-2 receptors coexpress with adenosine A(2A) and CB1 cannabinoid receptors, leading to functional interactions.

The protein and messenger RNA (mRNA) contents of A(2A), D-2, and CB1 receptors were quantified in postmortem prefrontal cortex of subjects

with schizophrenia.

The study was performed in subjects suffering schizophrenia (n = 31) who mainly died by suicide, matched with non-schizophrenia suicide buy LXH254 victims (n = 13) and non-suicide

controls (n = 33). The density of receptor proteins was evaluated by immunodetection techniques, and their relative mRNA expression was quantified by quantitative real-time polymerase chain reaction.

In schizophrenia, the densities of A(2A) (90 +/- 6%, n = 24) and D-2-like receptors (95 +/- 5%, n = 22) did not differ from those in controls (100%). Antipsychotic treatment did not induce changes in the protein expression. In contrast, the immunodensity of CB1 receptors was significantly decreased (71 +/- 7%, n = 11; p < 0.05) in antipsychotic-treated subjects with schizophrenia but not in drug-free subjects (104 +/- 13%, n = 11). The relative mRNA amounts encoding for A(2A), D-2, and CB1 receptors were similar

in brains of drug-free, antipsychotic-treated subjects with schizophrenia and controls.

The findings suggest that antipsychotics induce down-regulation of CB1 receptors in brain. Since A(2A), D-2, and CB1 receptors coexpress on brain GABAergic neurons and reductions in markers of GABA neurotransmission have been identified in schizophrenia, a lower density of CB1 receptor induced by antipsychotics could represent an adaptative mechanism Chlormezanone that reduces the endocannabinoid-mediated suppression of GABA release, contributing to the normalization of cognitive functions in the disorder.”
“Spermine (SPM) and spermidine, endogenous polyamines with the ability to modulate various ion channels and receptors in the brain, exert neuroprotective, antidepressant, antioxidant, and other effects in vivo such as increasing longevity. These polyamines are preferably accumulated in astrocytes, and we hypothesized that SPM increases glial intercellular communication by interacting with glial gap junctions. The results obtained in situ, using Lucifer yellow propagation in the astrocytic syncitium of 21-25-day-old rat CA1 hippocampal slices, showed reduced coupling when astrocytes were dialyzed with standard intracellular solutions without SPM.

Median patient age was 21 years (range, 5 months-39 years) Lesio

Median patient age was 21 years (range, 5 months-39 years). Lesion locations included extremities in 13, faces in eight, and trunks Selleck Temsirolimus in two. The standardized sclerosing foam was prepared using Tessari’s method to mix room air with 5% sodium morrhuate in a 4:1 ratio. Sclerotherapy was performed by the “”filling-defects”" technique under fluoroscopy. Postsclerotherapy surveillance was done at 6 months after the last session. Treatment response was assessed clinically and by means of lesion size measurement with magnetic resonance imaging. During the treatment and the follow-tap period, adverse events and adverse drug reactions were recorded. Specific complications

were classified as major or minor.

Results: A total of 58 treatment sessions were performed (mean, 3 sessions per patient; range, 1-6 sessions). At the 6-month follow-up, 15 patients (65.2%) showed a total disappearance of treated malformations, six (26.1%) showed a reduction in malformation size of > 50%, and two (8.7%) showed a reduction in malformation size of <= 50%. The overall patient-reported outcome Oligomycin A nmr teas excellent in 11 (47.8%), good in 8 (34.8%), or moderate in 4 (17.4%). Minor complications included swelling and inflammatory reaction per session, mild pain in 17

sessions (29.3%), and skin blister at the injection site in two sessions (3.4%), which resolved spontaneously within several days to 2 weeks. No major complications occurred.

Conclusion: Fluoroscopic guidance could have great promise in foam sclerotherapy of peripheral venous malformations, although larger studies are necessary to determine the advantages of this technique over other sclerotherapeutic methods. (J Vasc Surg 2009;49:961-7.)”
“Introduction: Often groin recurrences after varicose vein surgery are diagnosed and classified with the

help of a duplex ultrasound scan. There are, however, no studies indicating if duplex ultrasound scans can reliably distinguish between the different forms of recurrent vessels, ie, neovascularization or a residual stump. To address this issue, we have conducted a prospective study in which ultrasound scan assessment Beta adrenergic receptor kinase of groin recurrences was compared to the histological classification of the recurrent groin veins.

Materials and Methods: All patients undergoing redo-surgery for symptomatic groin recurrences after previous stripping of the greater saphenous vein (GSV) during a 1-year period (May 2006-May 2007) were included in the study. Preoperatively, all patients had a duplex-ultrasound scan examination of the groin vessels. Based on the duplex scan findings, the recurrent veins in the groin were classified as either a residual stump or neovascularization. During the redo-surgery, a specimen of the recurrent groin veins was obtained and underwent histologic evaluation. Based on histologic criteria, the recurrence was also classified as a residual stump or neovascularization.

Similarly, patients who presented with < 10 NIHSS had a better

Similarly, patients who presented with < 10 NIHSS had a better 3-month outcome than those with > 10 NIHSS

[OR 0.21 (0.08-0.61), p value=0.004].

Conclusion Ischemic stroke patients without arterial occlusion on DSA have a higher risk of cerebral infarction and disability particularly in men, patients over 65 years of age and with NIHSS >= 10. The cause of infarction may have been arterial obstruction with spontaneous recanalization or small vessel occlusion not visible on DSA.”
“Memory consolidation is the process by which newly learned information is stabilized into long-term memory (LTM). Considerable evidence indicates that retrieval of a consolidated memory returns it to a labile state that requires it to be restabilized. Consolidation of new fear memories has been shown to require de novo RNA and protein synthesis in the lateral nucleus of the amygdala (LA). We have previously shown that https://www.selleckchem.com/products/wh-4-023.html de novo protein synthesis in the LA is required for reconsolidation of auditory fear memories. One key question is whether protein synthesis during reconsolidation depends on already Lonafarnib cost existing mRNAs or on synthesis of new mRNAs in the amygdala. In the present study, we examined the effect of mRNA synthesis

inhibition during consolidation and reconsolidation of auditory fear memories. We first show that intra-LA infusion of two different mRNA inhibitors dose-dependently impairs long-term memory but leaves short-term memory (STM) intact. Next, we show that intra-LA infusion of the same inhibitors dose-dependently blocks post-reactivation long-term memory (PR-LTM), whereas post-reactivation short-term memory (PR-STM) is left intact. Furthermore, the same treatment

in the absence of memory reactivation has no effect. Together, these results show that both consolidation and reconsolidation of auditory fear memories require de novo mRNA synthesis and are equally sensitive to disruption of de novo mRNA synthesis in the LA.”
“Introduction Patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) have a high risk of having distant metastases or second primary tumors. We prospectively evaluate the clinical usefulness of F-18-fluoro-2-deoxyglucose unless positron emission tomography (F-18-FDG PET), extended-field multi-detector computed tomography (MDCT), and their side-by-side visual correlation for the detection of distant malignancies in these two tumors at presentation.

Materials and methods A total of 160 patients with SCC of the oropharynx (n=74) or hypopharynx (n=86) underwent F-18-FDG PET and extended-field MDCT to detect distant metastases or second primary tumors. Suspected lesions were investigated by means of biopsy, clinical, or imaging follow-up.

Results Twenty-six (16.3%) of our 160 patients were found to have distant malignancy. Diagnostic yields of F-18-FDG PET and MDCT were 12.5% and 8.1%, respectively.

The primary objective of the study was to evaluate the effect of

The primary objective of the study was to evaluate the effect of pretreatment with naltrexone on the see more subjective response to amphetamine, using a Visual Analog Scale. The secondary objective was to investigate the effects of naltrexone on physiological and biochemical responses to amphetamine, as measured by changes in blood pressure, heart rate, skin conductance, and cortisol. Naltrexone significantly attenuated the subjective effects produced by dexamphetamine

in dependent patients (p < 0.001). Pretreatment with naltrexone also significantly blocked the craving for dexamphetamine (p < 0.001). There was no difference between the groups on the physiological measures. The results suggest that the subjective effects of amphetamine could be modulated via the endogenous opioid system. The potential of naltrexone as an adjunct pharmaceutical for amphetamine dependence

is promising.”
“Background: The Leapfrog Group established evidence-based standards for abdominal aortic aneurysm (AAA) repair, including targets for case volume and perioperative beta-blocker usage. The purpose of this study was to determine whether meeting these benchmarks correlated with improved patient outcomes over time.

Methods: We studied California hospitals that responded to consecutive Leapfrog Group Hospital Quality and Safety Surveys between 2000 and 2005. Survey results of compliance with Leapfrog standards were linked to patient outcomes for AAA repair using the California state discharge database for the corresponding years. A random-effects Poisson regression analysis was performed to measure the effect of meeting beta-blocker and case volume Selleckchem E7080 standards on hospital mortality and average length of stay after elective open and endovascular AAA repair (EVAR) during the early (2000-2002) and later (2003-2005) phase of Leapfrog implementation.

Results: PDE4B Among 140 hospitals that performed open AAA repair, 25 (17.4%) met the Leapfrog case volume standard, 32 (22.2%) were compliant

with routine perioperative beta-blocker use, 5 hospitals (3.5%) met both criteria, and 78 control hospitals failed to meet either standard. After controlling for temporal differences in hospital and patient characteristics, hospitals that implemented a policy for perioperative beta-blocker usage were found to have an estimated 51% reduction of in-hospital mortality (relative risk, 0.49; 95% confidence interval, 0.24-0.99; P < .05) after open AAA repair cases compared with control hospitals over time. There was no improvement in mortality outcomes over time, however, after open AAA repair in hospitals meeting case volume standards. Among 111 California hospitals in which EVAR was performed, there was an estimated 61% reduction of in-hospital mortality over time (relative risk, 0.39; 95% confidence interval, 0.07-1.80) among hospitals meeting Leapfrog case volume standards compared with control hospitals, although these results did not reach statistical significance.

2%] vs 185 [2 9%], 0 91 [0 74-1 12]; p=0 3785)

Interp

2%] vs 185 [2.9%], 0.91 [0.74-1.12]; p=0.3785).

Interpretation Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned.”
“Background Several mortality estimates for the Darfur conflict have been reported since 2004, but few accounted for conflict dynamics such as changing displacement and causes of deaths. We analyse changes over time for crude and cause-specific LY2874455 mortality rates, and assess the effect of displacement on mortality rates.

Methods Retrospective mortality surveys were gathered from

an online database. Quasi-Poisson models were used to assess mortality rates with place and period in which the survey was done, and the proportions of displaced people in the samples were the explanatory variables. Predicted mortality rates for five periods were computed and applied to population data taken from the UN’s series about Darfur to obtain the number of deaths.

Findings 63 of

107 mortality surveys met all criteria for analysis. Our results show significant reductions in mortality rates from early 2004 to the end of 2008, although rates were higher during deployment of fewer humanitarian aid workers. In general, the reduction in rate was more important for violence-related than for diarrhoea-related mortality. Displacement correlated with increased rates of deaths associated with diarrhoea, but also with reduction in violent deaths. We estimated the excess number of deaths to be 298 check details 271 (95% CI 178 258-461 520).

Interpretation Although violence was the main cause of death during 2004, diseases have been the cause of most deaths since 2005, with displaced populations being the triclocarban most susceptible. Any reduction in humanitarian assistance could lead to worsening mortality rates, as was the case between mid 2006 and mid 2007.”
“Background Anticipation of the types of injuries that occur in modem warfare is essential to plan operations and maintain a healthy military. We aimed to identify the

diagnoses that result in most medical evacuations, and ascertain which demographic and clinical variables were associated with return to duty.

Methods Demographic and clinical data were prospectively obtained for US military personnel who had been medically evacuated from Operation Iraqi Freedom or Operation Enduring Freedom (January, 2004-December, 2007). Diagnoses were categorised post hoc according to the International Classification of Diseases codes that were recorded at the time of transfer. The primary outcome measure was return to duty within 2 weeks.

Findings 34006 personnel were medically evacuated, of whom 89% were men, 91% were enlisted, 82% were in the army, and 86% sustained an injury in Iraq.

While group II agonists are effective in several animal models of

While group II agonists are effective in several animal models of schizophrenia, they are reported to lack efficacy in moderating the effects of phencyclidine (PCP) on prepulse inhibition of acoustic startle in animal models of sensory processing deficits found in this disorder.

The objective of this study was to re-examine the efficacy of a group II metabotropic glutamate agonist and NAAG peptidase inhibitors in prepulse inhibition models of schizophrenia across two strains of mice.

The method used was an assay to determine the efficacy

of these drugs in moderating the reduction in prepulse inhibition of acoustic startle in mice treated with PCP and www.selleckchem.com/products/bv-6.html d-amphetamine.

The group II agonist LY354740 (5 and 10 mg/kg) moderated the effects of PCP on prepulse inhibition of acoustic startle in DBA/2 but not C57BL/6 mice. In contrast, two NAAG peptidase inhibitors, ZJ43 (150 mg/kg) and 2-PMPA (50, 100, and 150 mg/kg), did not significantly affect the PCP-induced reduction in prepulse inhibition in either strain.

These data demonstrate that the efficacy of group II agonists in this model of sensory motor processing is strain-specific in mice. The difference between the effects of the group II agonist and the peptidase

inhibitors in the DBA/2 mice may relate to the difference in efficacy of NAAG and the agonist at mGluR2.”
“The complex Morin Hydrate interactions between biomolecules and the consequences of these interactions BAY 11-7082 cost are known as biomolecular events. Such events particularly in proteins play a key role in several aspects of proteomics. The major source of extraction of biomolecular events is the biomedical literature. Event trigger word detection is generally the first step in computationally mining the biomedical literature for biomolecular events. In this work, we study how to efficiently map the dependency graph of a candidate sentence

into semantic/syntactic features, and use these semantic/syntactic features to detect bio-event triggers from the biomedical literature. The key factor in our method was the use of the hash operation to iteratively compute the dependency graph and utilize the properties of the hash operation to map the dependency graph into neighborhood hash features. The experimental results showed that neighborhood hash features can effectively represent the semantic/syntactic information in the sentence dependency graph. Furthermore, neighborhood hash features and basic features are complementary in the detection of biomolecular triggers. This approach, based on neighborhood hash features, achieved state-of-the-art performance on BioNLP datasets with respect to comparable evaluations. (C) 2012 Elsevier Ltd. All rights reserved.

Ten patients had progression to end stage renal disease-3 dialysi

Ten patients had progression to end stage renal disease-3 dialysis, 6 transplant, and 1 chronic kidney disease stage 5. Two patients had stage 5 chronic kidney disease at initial presentation. A comparison of preoperative estimated glomerular filtration rate between patients with and those without end stage renal disease revealed a lower preoperative selleck compound estimated glomerular filtration rate in the former group (43.4 vs 75.4 ml/minute/1.73 m(2), p = 0.01). Of the patients 53% had an improved or stable antihypertensive therapeutic index at last followup, although no improvement in mean overall antihypertensive therapeutic index

was noted (4.7 pre-laparoscopic cyst decortications vs 7.0 post-laparoscopic cyst decortications, p = 0.28).

Conclusions: Durable pain relief but not hypertension control was seen at 10-year followup. Preoperative estimated glomerular filtration rate is a strong learn more predictor of post-laparoscopic cyst decortication progression to end stage renal disease. A cautious approach with laparoscopic cyst decortication should be taken in patients with poor preoperative renal function.”
“Fusarium oxysporum is an important plant pathogen that causes severe damage of many economically important crop species. Various microorganisms

have been shown to inhibit this soil-borne plant pathogen, including non-pathogenic F. oxysporum strains. In this study, F. oxysporum wild-type (WT) MSA 35, a biocontrol multispecies consortium that consists of a fungus and numerous rhizobacteria mainly Ibrutinib manufacturer belonging to gamma-proteobacteria, was analyzed by two complementary metaproteomic approaches (2-DE combined with MALDI-Tof/Tof MS and 1-D PAGE combined with LC-ESI-MS/MS) to identify fungal or bacterial factors potentially involved in antagonistic or synergistic interactions between the consortium

members. Moreover, the proteome profiles of F. oxysporum WT MSA 35 and its cured counter-part CU MSA 35 (WT treated with antibiotics) were compared with unravel the bacterial impact on consortium functioning. Our study presents the first proteome mapping of an antagonistic F. oxysporum strain and proposes candidate proteins that might play an important role for the biocontrol activity and the close interrelationship between the fungus and its bacterial partners.”
“BACKGROUND

Neutrophils are the predominant phagocytes that provide protection against bacterial and fungal infections. Genetically determined neutrophil disorders confer a predisposition to severe infections and reveal novel mechanisms that control vesicular trafficking, hematopoiesis, and innate immunity.

METHODS

We clinically evaluated seven children from five families who had neutropenia, neutrophil dysfunction, bone marrow fibrosis, and nephromegaly.