LRRK2 G2019S and I2020T mutations are not common in Alzheimer's disease and vascular dementia.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to E Lee.
Explore the source record for details and available documents.
An open question about the dynamical behavior of materials is how phase transition occurs in highly nonequilibrium systems. One important class of study is the excitation of a solid by an ultrafast, intense laser. The preferential heating of electrons by the laser field gives rise to initial states dominated by hot electrons in a cold lattice. Using a femtosecond laser pump-probe approach, we have followed the temporal evolution of the optical properties of such a system. The results show interesting correlation to nonthermal melting and lattice disordering processes. They also reveal a liquid-plasma transition when the lattice energy density reaches a critical value.
Although T-cell CD28/CD40 costimulation blockade represents a powerful mechanism to promote immune tolerance during murine allotransplantation, it has not yet been successfully translated to clinical transplantation. We determined the impact of natural killer (NK) cells on costimulation blockade-resistant rejection of donor bone marrow. We found that NK cells represent a potent barrier to engraftment: host NK depletion led to increased donor stem cell survival, increased mixed hematopoietic chimerism and to engraftment of low doses of donor marrow (1 x 10(8)/kg) that were otherwise rejected. To understand the mechanisms of NK alloreactivity, we employed an in vivo NK-specific cytotoxicity assay. We found that an increased proportion of target cells were killed between days 2 and 8 after cell transfer, and that NK killing of parental targets was inducible: NK cells preprimed with allotargets were more efficient at their elimination upon reexposure. Finally, both transplant and in vivo NK-killing models were used to determine the contribution of LFA-1 to NK alloreactivity. Blockade of LFA-1 led to decreased NK-mediated killing, and increased alloengraftment. These results identify NK alloreactivity as an integral component to costimulation blockade-resistant rejection, and suggest that its inhibition may represent an important target in the clinical translation of tolerance-induction transplantation.
In a patient-controlled study, the authors demonstrated a significantly higher prevalence of rostral ventrolateral medulla (VLM) compression in hypertensive patients with hemifacial spasm (HFS) compared with age-, sex-, race-, disease duration-, and disease severity-matched normotensive patients with HFS (p = 0.02). Hypertensive HFS patients were more likely to have a greater severity of neurovascular compression at the VLM compared with normotensive HFS patients (p = 0.008). VLM compression is associated with risk of hypertension in this study population.
Explore the source record for details and available documents.
The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular interactions that arise from published experimental research and to provide this information, as well as tools to enable data analysis, freely to researchers worldwide. BIND data are curated into a comprehensive machine-readable archive of computable information and provides users with methods to discover interactions and molecular mechanisms. BIND has worked to develop new methods for visualization that amplify the underlying annotation of genes and proteins to facilitate the study of molecular interaction networks. BIND has maintained an open database policy since its inception in 1999. Data growth has proceeded at a tremendous rate, approaching over 100 000 records. New services provided include a new BIND Query and Submission interface, a Standard Object Access Protocol service and the Small Molecule Interaction Database (http://smid.blueprint.org) that allows users to determine probable small molecule binding sites of new sequences and examine conserved binding residues.
BACKGROUND: Compared with the original Goeckerman therapy devised by Dr Goeckerman in the 1930s, modern modified Goeckerman therapy in the second millennium shows significantly enhanced efficacy by improvements in technology (e.g. narrowband UVB) and the possibility of adding other relatively safe therapeutic options for more resistant cases to enhance efficacy without compromising the basic safety profile. METHODS: For approximately 6 months, psoriasis patients undergoing Goeckerman therapy at the UCSF Psoriasis Center were followed from admission to discharge. A total of 25 consecutive psoriasis patients were treated with the Goeckerman regimen until (near-) clearance or for a maximum period of 3 months, and their weekly improvements in terms of PASI (psoriasis area and severity index) were recorded. RESULTS: In all, 100% reached PASI 75 by 12 weeks of treatment. In fact, by 8 weeks, 95% reached PASI 75 and most of the patients were discharged within 2 months. CONCLUSIONS: The onset of treatment effect was rapid. Goeckerman therapy is still a valuable and important part of the psoriatic armamentarium.
Explore the source record for details and available documents.
Although the megamitochondria (MM) were localized in various pathological conditions, normal retina of some mammalian species was reported to include MM for various physiological roles. However, it was not clearly confirmed whether the MM is present in the retina of lower vertebrate as well. In this study, we tried to show the presence of the MM in the zebrafish retina using electron microscopic technique. In all the photoreceptors including rods, cones and double cones of the zebrafish retina, MM were observed in the ellipsoid of inner segment. In the photoreceptor epllipsoid of the zebrafish retina, the mitochondria located in the central portion of the ellipsoid had a highly electron-dense matrix, which were accompanied by the mitochondria with electron-lucent matrix in the apical portion of the ellipsoid. The presence of MM was more clearly discernable in the rods, which were localized under the double cones. This finding is somewhat different from those observed in the previous studies because MM were localized in the inner segment of cones, but were not in those of rods in the case of mammalian retina. Although the exact physiological meaning for the presence of MM in some vertebrate species should be further studied, the present study could show that the MM in the ellipsoid of the retinal photoreceptors was not only restricted in some mammalian species.
A 65-year-old Caucasian man with myelodysplasia was admitted with autoimmune hemolytic anemia and a Hb of 5.6 g/dL. The patient's serum contained anti-K; the DAT on the patient's RBCs reacted 3+ with anti-IgG and 3+ with anti-C3d. K- RBC units were transfused, but there was no sustained increase in Hb level. The samples were referred to the reference laboratory of the National Blood Service. The DAT results remained the same, with anti-K detected only in the serum. An eluate prepared from the patient's DAT-positive RBCs revealed anti-Kp(b) specificity. This study reports an unusual case of autoanti-Kp(b), which is different from previously published cases in that no free anti-Kp(b) was detectable in the serum.
New York City's first syndromic surveillance systems were established in 1995 to detect outbreaks of waterborne illness. In 1998, daily monitoring of ambulance dispatch calls for influenza-like illness began. After the 2001 World Trade Center attacks, concern about biologic terrorism led to the development of surveillance systems to track chief complaints of patients reporting to emergency departments, over-the-counter and prescription pharmacy sales, and worker absenteeism. These systems have proved useful for detecting substantial citywide increases in common viral illnesses (e.g., influenza, norovirus, and rotavirus). However, the systems have not detected more contained outbreaks earlier than traditional surveillance. Future plans include monitoring school health and outpatient clinic visits, augmenting laboratory testing to confirm syndromic signals, and conducting evaluation studies to identify which of these systems will be continued for the long term.
Previously it has been shown that the hippocampus and neocortex can spontaneously reactivate ensemble activity patterns during post-behavioral sleep and rest periods. Here we examined whether such reactivation also occurs in a subcortical structure, the ventral striatum, which receives a direct input from the hippocampal formation and has been implicated in guidance of consummatory and conditioned behaviors. During a reward-searching task on a T-maze, flanked by sleep and rest periods, parallel recordings were made from ventral striatal ensembles while EEG signals were derived from the hippocampus. Statistical measures indicated a significant amount of reactivation in the ventral striatum. In line with hippocampal data, reactivation was especially prominent during post-behavioral slow-wave sleep, but unlike the hippocampus, no decay in pattern recurrence was visible in the ventral striatum across the first 40 min of post-behavioral rest. We next studied the relationship between ensemble firing patterns in ventral striatum and hippocampal ripples-sharp waves, which have been implicated in pattern replay. Firing rates were significantly modulated in close temporal association with hippocampal ripples in 25% of the units, showing a marked transient enhancement in the average response profile. Strikingly, ripple-modulated neurons in ventral striatum showed a clear reactivation, whereas nonmodulated cells did not. These data suggest, first, the occurrence of pattern replay in a subcortical structure implied in the processing and prediction of reward and, second, a functional linkage between ventral striatal reactivation and a specific type of high-frequency population activity associated with hippocampal replay.
INTRODUCTION: This study prospectively followed women over the course of pregnancy to assess the impact of depression and/or antidepressant treatment on obstetrical outcome. METHOD: Sixty-four outpatient women with an Axis I diagnosis of major depressive disorder or no psychiatric history were followed in each trimester of pregnancy with administration of the CES-D. A subset of the women with depression received treatment with fluoxetine during pregnancy. Subjects with a CES-D score greater than 16 at any time point were further assessed for the presence of an active major or minor depressive episode. Primary outcome variables included infant gestational age, birth weight, Apgar score, and admission to the neonatal intensive care unit. RESULTS: Analyzable data were available for 62 women. No significant differences were found in outcome variables between those women with exposure to medication and/or prenatal depressed mood and those women without a history of depression. CONCLUSIONS: In contrast to other studies, our study did not demonstrate an adverse effect of fluoxetine exposure per se on obstetrical outcome. In addition, we did not find a significant impact of depression during pregnancy on obstetrical outcome.
BACKGROUND: Indicated as monotherapy for severe psoriasis in adults, acitretin (Soriatane) can be used in combination therapy or as a 'disease-stabilizing, maintenance' agent. While its efficacy for psoriasis and other disorders of keratinization is well established, its safety is often a concern for many dermatologists. The possible side effects associated with short-term treatment of oral retinoids include mucocutaneous effects, elevation in serum lipid chemistries and liver enzymes, and teratogenicity. However, the only possible long-term, cumulative side effect is skeletal and ligamentous calcification such as hyperostosis. There is a specific syndrome of hyperostosis associated with oral retinoids called DISH (diffuse idiopathic skeletal hyperostosis). OBJECTIVE: To examine the incidence of DISH syndrome in long-term acitretin use for psoriasis and to quantify the incidence of other side effects. METHODS: All patients seen at the UCSF Psoriasis and Skin Treatment Center who had been on acitretin for more than 1 year were identified. RESULTS: A chart review of these patients revealed no X-ray-confirmed cases of DISH syndrome, minimal changes in coronary heart disease risk indicators, and extremely rare significant elevation of liver enzymes. CONCLUSION: Acitretin does not appear to cause significant long-term side effects at low doses; the implications for thousands of patients are that use of this medication can be continued for long periods of time with routine monitoring.
BACKGROUND: Type 1 T cells are hypothesized to be central in the immunopathogenesis of psoriasis. Through elaboration of interferon (IFN)-gamma, type 1 T cells regulate the expression of many 'downstream' inflammatory genes, including an array of chemokines that regulate leucocyte trafficking and activation in skin lesions. Accordingly, disease progression and/or severity might be controlled by the degree to which differing cytokines and chemokines are overexpressed in focal skin regions. To examine this possibility, we studied two forms of chronic psoriasis vulgaris that differ significantly in overall severity and progression: small plaque (SP) psoriasis occurring in Korean patients, and large plaque (LP) psoriasis occurring in North American patients. OBJECTIVES: To characterize LP and SP psoriasis vulgaris with respect to expression of proinflammatory genes that define the type 1 T-cell axis in skin lesions [genes encoding interleukin (IL)-12, IFN-gamma, and IFN-gamma-regulated chemokines or inflammatory mediators]. METHODS: Total cellular RNA of skin samples from groups of patients with LP or SP psoriasis was analysed by quantitative reverse transcription-polymerase chain reaction (TaqMan analysis) to compare the differences in mRNA expression of genes related to the IFN-gamma pathway. RESULTS: The mRNA expression of keratin 16, CD25, IFN-gamma, IL-12 p40, signal transducer and activator of transcription-1, inducible nitric oxide synthase, IL-8, macrophage inflammatory protein-3alpha, monocyte chemoattractant protein-1, S100A12, IFN-gamma-inducible protein of 10 kDa, IFN-inducible T-cell alpha-chemoattractant and monokine induced by IFN-gamma was increased in the lesions of both LP psoriasis and SP psoriasis. However, IL-18 mRNA expression was significantly different in the lesions of LP psoriasis in comparison with those of SP psoriasis. CONCLUSIONS: The results indicate that proinflammatory type 1 genes regulated by IFN-gamma are similarly increased in both SP and LP psoriasis, but a potential difference in IL-18 exists between these disease forms. The consistent activation of this set of genes argues for a central role of IFN-gamma as a molecular regulator of inflammation in these distinct subtypes of psoriasis vulgaris. In contrast, disease extent/severity must be controlled by yet other factors.
The limited supply of reagent human polyclonal antibodies to high prevalence antigens, like Js(b), is driving the search for alternative reagents. Murine immunoglobulin G (IgG) monoclonal antibodies (Mabs) and their humanized chimaeric IgM isoforms can now be used for typing patients and screening donors. Antigen typing of red blood cells (RBC) with a positive direct antiglobulin test (DAT) is also possible using these antibodies. Blood from patients with sickle cell disease and African donors were tested with reagent anti-Js(b), murine Mab IgG anti-Js(b) [murine immunochemistry monoclonal antibody-8 (MIMA-8)], and humanized chimaeric IgM anti-Js(b) [human immunochemistry monoclonal antibody-8 (HIMA-8)] by haemagglutination and gel cards. RBC samples that were DAT positive were used to evaluate the humanized chimaeric IgM monoclonal anti-Fy(a) (HIMA-19). RBC samples (n = 243) of known Js(b) type were tested in parallel with MIMA-8 and reagent anti-Js(b), and 132 samples were tested with MIMA-8 in gel cards and HIMA-8 by direct tube testing. No discrepant results were obtained. DAT-positive RBC samples (n = 27) were correctly phenotyped using HIMA-19. We conclude that MIMA-8 is suitable for screening donors and typing patient RBCs. Testing MIMA-8 with gel cards containing anti-mouse IgG enables the screening of donors by automated methods. Humanized chimaeric IgM anti-Js(b) and anti-Fy(a) are suitable as typing reagents by direct agglutination methods.
This study of marsupial hearts explored the aerobic capacities of this group of mammals; recent information suggests that marsupials possess higher aerobic abilities than previously accepted. Characteristics such as heart mass, mitochondrial features and capillary parameters were examined. A comprehensive study of the heart of red kangaroos was included because of the high maximum oxygen consumption of this species. Goats were also included as a reference placental mammal. Marsupials have a heart that is generally larger than that of placentals. The allometric equation for the relationship between heart mass and body mass for marsupials was M(h)=7.5M(b)(0.944) (M(h) in g and M(b) in kg); the equivalent equation for placental mammals was M(h)=6.0M(b)(0.97). Mitochondrial volume density and inner mitochondrial surface density do not differ between the two mammal groups; although capillary parameters indicated a lower capillary volume in marsupials. Heart size appears to be the major difference between the two groups. The overall pattern seen in marsupials is similar to that of "athletic" placentals and indicates a relatively high aerobic potential.
Explore the source record for details and available documents.