Dr. James  Howell  Md image

Dr. James Howell Md

5301 E. Huron River Dr.
Ann Arbor MI 48106
734 124-4108
Medical School: Other - Unknown
Accepts Medicare: No
Participates In eRX: No
Participates In PQRS: No
Participates In EHR: No
License #: 4301082884
NPI: 1104994755
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New furoquinoline alkaloid and flavanone glycoside derivatives from the leaves of Oricia suaveolens and Oricia renieri (Rutaceae). - Natural product research
Fractionation of the methanol extract of the leaves of Oricia renieri and Oricia suaveolens (Rutaceae) led to the isolation of 13 compounds including the hitherto unknown furoquinoline alkaloid named 6,7-methylenedioxy-5-hydroxy-8-methoxy-dictamnine (1) and a flavanone glycoside named 5-hydroxy-4'-methoxy-7-O-[α-l-rhamnopyranosyl(1‴→5″)-β-d-apiofuranosyl]-flavanoside (2), together with 11 known compounds (3-13). The structures of the compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral data and comparison. All compounds isolated were examined for their activity against human carcinoma cell lines. The alkaloids 1, 5, 12, 13 and the phenolic 2, 8, 11 tested compounds exhibited non-selective moderate cytotoxic activity with IC50 8.7-15.9 μM whereas compounds 3, 4, 6, 7, 9 and 10 showed low activity.
Cobalt Boryl Complexes: Enabling and Exploiting Migratory Insertion in Base-Metal-Mediated Borylation. - Angewandte Chemie (International ed. in English)
Cobalt boryl complexes, which have only been sporadically reported, can be accessed systematically with remarkable (but controllable) variation in the nature of the M-B bond. Complexes incorporating a very strong trans σ-donor display unparalleled inertness, reflected in retention of the M-B bond even in the presence of extremely strong acid. By contrast, the use of the strong π-acceptor CO in the trans position, results in significant Co-B elongation and to labilization of the boryl ligand via unprecedented CO migratory insertion. Such chemistry provides a pathway for the generation of coordinative unsaturation, thereby enabling ligand substitution and/or substrate assimilation. Alkene functionalization by boryl transfer, a well-known reaction for noble metals such as Rh or Pt, can thus be effected by an 18-electron base-metal complex.© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Entrapment via synaptic-like connections between NG2 proteoglycan+ cells and dystrophic axons in the lesion plays a role in regeneration failure after spinal cord injury. - The Journal of neuroscience : the official journal of the Society for Neuroscience
NG2 is purportedly one of the most growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) produced after spinal cord injury. Nonetheless, once the severed axon tips dieback from the lesion core into the penumbra they closely associate with NG2+ cells. We asked if proteoglycans play a role in this tight cell-cell interaction and whether overadhesion upon these cells might participate in regeneration failure in rodents. Studies using varying ratios of CSPGs and adhesion molecules along with chondroitinase ABC, as well as purified adult cord-derived NG2 glia, demonstrate that CSPGs are involved in entrapping neurons. Once dystrophic axons become stabilized upon NG2+ cells, they form synaptic-like connections both in vitro and in vivo. In NG2 knock-out mice, sensory axons in the dorsal columns dieback further than their control counterparts. When axons are double conditioned to enhance their growth potential, some traverse the lesion core and express reduced amounts of synaptic proteins. Our studies suggest that proteoglycan-mediated entrapment upon NG2+ cells is an additional obstacle to CNS axon regeneration.Copyright © 2014 the authors 0270-6474/14/3416369-16$15.00/0.
Circumventing redox chemistry: synthesis of transition metal boryl complexes from a boryl nucleophile by decarbonylation. - Journal of the American Chemical Society
The very strong reducing capabilities of the boryllithium nucleophile (THF)2Li{B(NDippCH)2} (1, Dipp = 2,6-iPr2C6H3) render impractical its use for the direct introduction of the {B(NDippCH)2} ligand via metathesis chemistry into the immediate coordination sphere of transition metals (d(n), with n ≠ 0 or 10). Instead, 1 typically reacts with metal halide, amide and hydrocarbyl electrophiles either via electron transfer or halide abstraction. Evidence for the formation of M-B bonds is obtained only in the case of the d(5) system [{(HCDippN)2B}Mn(THF)(μ-Br)]2. Lower oxidation state metal carbonyl complexes such as Fe(CO)5 and Cr(CO)6 react with 1 via nucleophilic attack at the carbonyl carbon atom to give boryl-functionalized Fischer carbene complexes Fe(CO)4{C(OLi(THF)3)B(NDippCH)2} and Cr(CO)5{C(OLi(THF)2)B(NDippCH)2}. Although C-to-M boryl transfer does not occur for these formally anionic systems, more labile charge neutral bora-acyl derivatives of the type LnM{C(O)B(NDippCH)2} [LnM = Mn(CO)5, Re(CO)5, CpFe(CO)2] can be synthesized, which cleanly lose CO to generate M-B bonds. From a mechanistic standpoint, an archetypal organometallic mode of reactivity, carbonyl extrusion, has thus been shown to be applicable to the boryl ligand class, with (13)C isotopic labeling studies confirming a dissociation/migration pathway. These proof-of-methodology synthetic studies can be extended beyond boryl complexes of the group 7 and 8 metals (for which a number of versatile synthetic routes already exist) to provide access to complexes of cobalt, which have hitherto proven only sporadically accessible.
The Developmental Dynamics of Joining a Gang in Adolescence: Patterns and Predictors of Gang Membership. - Journal of research on adolescence : the official journal of the Society for Research on Adolescence
Researchers have examined the predictors of adolescent gang membership, finding significant factors in the neighborhood, family, school, peers, and individual domains. However, little is known about whether risk and protective factors differ in predictive salience at different developmental periods. The present study examines predictors of joining a gang, tests whether these factors have different effects at different ages, and whether they differ by gender using the Seattle Social Development Project (SSDP) sample (n=808). By age 19, 173 participants had joined a gang. Using survival analysis, results showed that unique predictors of gang membership onset included living with a gang member, antisocial neighborhood, and antisocial peer influences in the previous year. No time or gender interactions with predictors were statistically significant.
Preclinical research in Rett syndrome: setting the foundation for translational success. - Disease models & mechanisms
In September of 2011, the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the International Rett Syndrome Foundation (IRSF) and the Rett Syndrome Research Trust (RSRT) convened a workshop involving a broad cross-section of basic scientists, clinicians and representatives from the National Institutes of Health (NIH), the US Food and Drug Administration (FDA), the pharmaceutical industry and private foundations to assess the state of the art in animal studies of Rett syndrome (RTT). The aim of the workshop was to identify crucial knowledge gaps and to suggest scientific priorities and best practices for the use of animal models in preclinical evaluation of potential new RTT therapeutics. This review summarizes outcomes from the workshop and extensive follow-up discussions among participants, and includes: (1) a comprehensive summary of the physiological and behavioral phenotypes of RTT mouse models to date, and areas in which further phenotypic analyses are required to enhance the utility of these models for translational studies; (2) discussion of the impact of genetic differences among mouse models, and methodological differences among laboratories, on the expression and analysis, respectively, of phenotypic traits; and (3) definitions of the standards that the community of RTT researchers can implement for rigorous preclinical study design and transparent reporting to ensure that decisions to initiate costly clinical trials are grounded in reliable preclinical data.
Brain activity mapping in Mecp2 mutant mice reveals functional deficits in forebrain circuits, including key nodes in the default mode network, that are reversed with ketamine treatment. - The Journal of neuroscience : the official journal of the Society for Neuroscience
Excitatory-inhibitory imbalance has been identified within specific brain microcircuits in models of Rett syndrome (RTT) and other autism spectrum disorders (ASDs). However, macrocircuit dysfunction across the RTT brain as a whole has not been defined. To approach this issue, we mapped expression of the activity-dependent, immediate-early gene product Fos in the brains of wild-type (Wt) and methyl-CpG-binding protein 2 (Mecp2)-null (Null) mice, a model of RTT, before and after the appearance of overt symptoms (3 and 6 weeks of age, respectively). At 6 weeks, Null mice exhibit significantly less Fos labeling than Wt in limbic cortices and subcortical structures, including key nodes in the default mode network. In contrast, Null mice exhibit significantly more Fos labeling than Wt in the hindbrain, most notably in cardiorespiratory regions of the nucleus tractus solitarius (nTS). Using nTS as a model, whole-cell recordings demonstrated that increased Fos expression in Nulls at 6 weeks of age is associated with synaptic hyperexcitability, including increased frequency of spontaneous and miniature EPSCs and increased amplitude of evoked EPSCs in Nulls. No such effect of genotype on Fos or synaptic function was seen at 3 weeks. In the mutant forebrain, reduced Fos expression, as well as abnormal sensorimotor function, were reversed by the NMDA receptor antagonist ketamine. In light of recent findings that the default mode network is hypoactive in autism, our data raise the possibility that hypofunction within this meta-circuit is a shared feature of RTT and other ASDs and is reversible.
Focal cerebral ischemia after surgery in the "beach chair" position: the role of a congenital variation of circle of Willis anatomy. - Anesthesia and analgesia
A 50-year-old man underwent shoulder surgery in the beach chair position. His mean arterial blood pressure at arm level was approximately 65 mm Hg. Postoperatively, there was delayed awakening and a right hemiparesis. Radiologic evaluation revealed a congenital asymmetry of the circle of Willis that resulted in limited collateral flow to the left anterior and middle cerebral artery distributions. Similar anatomical variations are relatively common in the general population and may render some patients relatively and unpredictably more vulnerable to hypotension.
Comparison of the Paley method using chronological age with use of skeletal maturity for predicting mature limb length in children. - The Journal of bone and joint surgery. American volume
Treating patients with congenital or acquired limb-length inequality requires accurate estimations of limb length at skeletal maturity. There is controversy over the best indicator of maturity to be used for limb-length calculations. Paley popularized the multiplier method, in which chronological age is used, which has the virtue of simplicity but does not account for the wide variance in timing of the adolescent growth spurt. The purpose of this study was to determine whether the use of chronological age or the level of skeletal maturity provides more accurate limb-length predictions.We identified patients with limb-length inequality, for whom scanograms had been obtained before and at maturity, and who had had no surgical procedures on their normal lower limb. Skeletal maturity was determined with use of the Greulich and Pyle atlas, Tanner-Whitehouse-3 method, and simplified stages described by Sanders et al. The length of the lower extremity was compared with the ultimate limb length and the actual multiplier (final limb length divided by current limb length) for each point in time. A linear model was used to determine the log-transformed multipliers for the level of skeletal maturity, and Paley's multipliers were used for chronological age. Residual standard errors were determined to compare the results of the methods. We also conducted piecewise linear regression on each of the methods and used the residual standard errors to rank their performance and cross-validated the results.We identified twenty-four patients (twelve girls and twelve boys) who met the study criteria. Most subjects had had multiple scanograms along with skeletal age radiographs (average, 4.5) at different ages. When all ages are considered, the Paley method had the best overall performance, with residual standard errors that were typically =5 cm. However, the Paley method did not perform best for subjects at stage-2 skeletal maturity or above; in those cases, skeletal-maturity-based predictions had residual standard errors of <2 cm.While the Paley method, which is based on chronological age, provides reasonable estimates of ultimate limb length for most patients, use of skeletal-maturity determinations appears to provide better predictions of mature limb length during adolescence.
Epidemiologic investigation of immune-mediated polyradiculoneuropathy among abattoir workers exposed to porcine brain. - PloS one
In October 2007, a cluster of patients experiencing a novel polyradiculoneuropathy was identified at a pork abattoir (Plant A). Patients worked in the primary carcass processing area (warm room); the majority processed severed heads (head-table). An investigation was initiated to determine risk factors for illness.Symptoms of the reported patients were unlike previously described occupational associated illnesses. A case-control study was conducted at Plant A. A case was defined as evidence of symptoms of peripheral neuropathy and compatible electrodiagnostic testing in a pork abattoir worker. Two control groups were used - randomly selected non-ill warm-room workers (n = 49), and all non-ill head-table workers (n = 56). Consenting cases and controls were interviewed and blood and throat swabs were collected. The 26 largest U.S. pork abattoirs were surveyed to identify additional cases. Fifteen cases were identified at Plant A; illness onsets occurred during May 2004-November 2007. Median age was 32 years (range, 21-55 years). Cases were more likely than warm-room controls to have ever worked at the head-table (adjusted odds ratio [AOR], 6.6; 95% confidence interval [CI], 1.6-26.7), removed brains or removed muscle from the backs of heads (AOR, 10.3; 95% CI, 1.5-68.5), and worked within 0-10 feet of the brain removal operation (AOR, 9.9; 95% CI, 1.2-80.0). Associations remained when comparing head-table cases and head-table controls. Workers removed brains by using compressed air that liquefied brain and generated aerosolized droplets, exposing themselves and nearby workers. Eight additional cases were identified in the only two other abattoirs using this technique. The three abattoirs that used this technique have stopped brain removal, and no new cases have been reported after 24 months of follow up. Cases compared to controls had higher median interferon-gamma (IFNgamma) levels (21.7 pg/ml; vs 14.8 pg/ml, P<0.001).This novel polyradiculoneuropathy was associated with removing porcine brains with compressed air. An autoimmune mechanism is supported by higher levels of IFNgamma in cases than in controls consistent with other immune mediated illnesses occurring in association with neural tissue exposure. Abattoirs should not use compressed air to remove brains and should avoid procedures that aerosolize CNS tissue. This outbreak highlights the potential for respiratory or mucosal exposure to cause an immune-mediated illness in an occupational setting.

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