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Biomedical subjects

R M Howard

Publications and source records attributed to R M Howard.

At least 19 recordsLinked to original sources
PubMed2001

Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord are restricted to a glial lineage.

Proliferating populations of undifferentiated neural stem cells were isolated from the embryonic day 14 rat cerebral cortex or the adult rat subventricular zone. These cells were pluripotent through multiple passages, retaining the ability to differentiate in vitro into neurons, astrocytes, and oligodendrocytes. Two weeks to 2 months after engraftment of undifferentiated, BrdU-labeled stem cells into the normal adult spinal cord, large numbers of surviving cells were seen. The majority of the cells differentiated with astrocytic phenotype, although some oligodendrocytes and undifferentiated, nestin-positive cells were detected; NeuN-positive neurons were not seen. Labeled cells were also engrafted into the contused adult rat spinal cord (moderate NYU Impactor injury), either into the lesion cavity or into the white or gray matter both rostral and caudal to the injury epicenter. Up to 2 months postgrafting, the majority of cells either differentiated into GFAP-positive astrocytes or remained nestin positive. No BrdU-positive neurons or oligodendrocytes were observed. These results show robust survival of engrafted stem cells, but a differentiated phenotype restricted to glial lineages. We suggest that in vitro induction prior to transplantation will be necessary for these cells to differentiate into neurons or large numbers of oligodendrocytes.

Animals↗
PubMed2001

Kwashiorkor in the United States: fad diets, perceived and true milk allergy, and nutritional ignorance.

BACKGROUND: Kwashiorkor is the edematous form of protein-energy malnutrition. It is associated with extreme poverty in developing countries and with chronic malabsorptive conditions such as cystic fibrosis in developed countries. Rare cases of kwashiorkor in affluent countries unrelated to chronic illness have been reported. We present 12 cases of kwashiorkor unrelated to chronic illness seen over 9 years by pediatric dermatologists throughout the United States, and discuss common causative themes in this easily preventable condition. OBSERVATIONS: Twelve children were diagnosed as having kwashiorkor in 7 tertiary referral centers throughout the United States. The diagnoses were based on the characteristic rash and the overall clinical presentation. The rash consisted of an erosive, crusting, desquamating dermatitis sometimes with classic "pasted-on" scale-the so-called flaky paint sign. Most cases were due to nutritional ignorance, perceived milk intolerance, or food faddism. Half of the cases were the result of a deliberate deviation to a protein-deficient diet because of a perceived intolerance of formula or milk. Financial and social stresses were a factor in only 2 cases, and in both cases social chaos was more of a factor than an absolute lack of financial resources. Misleading dietary histories and the presence of edema masking growth failure obscured the clinical picture in some cases. CONCLUSIONS: Physicians should consider the diagnosis of kwashiorkor in children with perceived milk allergies resulting in frequent dietary manipulations, in children following fad or unorthodox diets, or in children living in homes with significant social chaos. The presence of edema and "flaky paint" dermatitis should prompt a careful dietary investigation.

Diet Fads↗
PubMed1999

A PP2A regulatory subunit positively regulates Ras-mediated signaling during Caenorhabditis elegans vulval induction.

We describe evidence that a regulatory B subunit of protein phosphatase 2A (PP2A) positively regulates an RTK-Ras-MAP kinase signaling cascade during Caenorhabditis elegans vulval induction. Although reduction of sur-6 PP2A-B function causes few vulval induction defects in an otherwise wild-type background, sur-6 PP2A-B mutations suppress the Multivulva phenotype of an activated ras mutation and enhance the Vulvaless phenotype of mutations in lin-45 raf, sur-8, or mpk-1. Double mutant analysis suggests that sur-6 PP2A-B acts downstream or in parallel to ras, but likely upstream of raf, and functions with ksr-1 in a common pathway to positively regulate Ras signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Catalytic mechanism and function of invariant glutamic acid 173 from the histone acetyltransferase GCN5 transcriptional coactivator.

Within chromatin, reversible acetylation of core histones is critical for transcriptional activation of eukaryotic target genes. The recent identification of intrinsic histone acetyltransferase (HAT) catalytic activity from a number of transcriptional co-activators (including yeast GCN5, p300/CBP, P/CAF, and TAFII250), has underscored the importance of protein acetylation in transcriptional control. The GCN5 family is the prototype for a diverse group of at least four distinct human HATs families. Although there is now a clear link between in vivo HAT catalytic activity and gene activation, little is known about the molecular mechanisms of histone acetylation. Herein, we report the first detailed biochemical study that probes the catalytic mechanism and the function of invariant glutamic acid 173 within the GCN5 family of HATs. Our results suggest that the HAT reaction involves the formation of a ternary complex (histones, acetyl-CoA, and enzyme) where the epsilon-amino group of histone lysine residues directly attacks the bound acetyl-CoA. The acetylation reaction requires deprotonation of the epsilon-amino group prior to nucleophilic attack. Employing site-directed mutagenesis, chemical modification, steady-state, and pH-dependent rate analysis, it is demonstrated that glutamic acid 173 is an essential catalytic residue, acting as a general base catalyst by deprotonating the histone substrate.

Acetyl Coenzyme A↗
PubMed1993

Changes in lipoprotein lipase activities in adipose tissue, heart and skeletal muscle during continuous or interrupted feeding.

Lipoprotein lipase (LPL) activities in parametrial and interscapular adipose tissue, soleus and adductor longus muscles and hearts of female rats were measured during progressive starvation, chow re-feeding after 24 h starvation and throughout dark and light phases in rats permitted unrestricted access to chow. Adipose-tissue LPL activities declined by 50% after 6 h starvation and continued to fall as the starvation period was extended to 24 h. Skeletal-muscle LPL activities dramatically increased between 9 and 12 h of starvation. Cardiac LPL activities increased 2.5-fold within 6 h of starvation, reaching a maximum after 12 h of starvation. Adipose-tissue LPL activities increased rapidly within 2 h of re-feeding chow ad libitum after 24 h starvation, achieving 'fed ad libitum' values after 6 h. Oxidative-skeletal-muscle LPL activities also increased after 2 h of refeeding and exceeded 'fed ad libitum' values throughout the 6 h re-feeding period. Cardiac LPL activities remained up-regulated for the 6 h of re-feeding. Adipose-tissue LPL activities exceeded those of cardiac or skeletal muscle throughout both light and dark phases. The lowest adipose-tissue LPL activities were observed at 9 h into the light phase. In contrast, cardiac LPL activity declined throughout the dark phase, with a minimum at 9 h into the dark phase. No such variation was observed for skeletal-muscle LPL activities. A diurnal nadir in plasma triacylglycerol (TG) concentrations coincided with the peak in cardiac LPL activities. The results demonstrate that, during unrestricted feeding and re-feeding after prolonged starvation, changes in skeletal-muscle and adipose-tissue LPL activities are neither reciprocal nor co-ordinate. Regulation of cardiac LPL activity during the diurnal cycle may be an important aspect of both of cardiac fuel selection and whole-body TG metabolism.

Adipose Tissue↗
PubMed1993

Mechanisms involved in the coordinate regulation of strategic enzymes of glucose metabolism.

In this review, we evaluate the relative regulatory importance of specific strategic enzymes (in particular glycogen synthase, acetyl-CoA carboxylase [ACC] and the pyruvate dehydrogenase complex [PDH]) for carbohydrate utilization as an anabolic precursor and as an energy substrate during the nutritional transitions between the fed and fasted states. The involvement of the specific protein kinases contributing to the inactivation of these enzymes by phosphorylation [cyclic AMP-dependent protein kinase, AMP-activated protein kinase and PDH kinase] in achieving each regulatory response is also assessed. We demonstrate a striking temporal correlation between hepatic glycogen mobilization and PDH and ACC inactivation by phosphorylation during the immediate postabsorptive period; in contrast, rates of hepatic glycogen synthesis and PDH and ACC expressed activities do not change in parallel during refeeding. The results are consistent with shifting of the primary sites of control for overall hepatic carbon flux during the fed-to-starved and starved-to-fed nutritional transitions achieved, at least in part, by a complex pattern of regulation by protein phosphorylation and metabolites which is critically dependent on the precise nutritional status. Data are also presented that demonstrate asynchronous suppression of glucose uptake/phosphorylation and pyruvate oxidation in cardiac and skeletal muscle during progressive starvation. Analogous asynchrony is observed in the reactivation of these processes in cardiac and skeletal muscle during refeeding after starvation. We provide evidence in support of the concept that selective suppression of pyruvate oxidation in oxidative muscles during early starvation and during the initial phase of refeeding is achieved because of differential sensitivity of glucose uptake/phosphorylation and pyruvate oxidation to lipid-fuel utilization. We discuss the relative importance of regulatory events governing local fatty acid production and utilization (via lipoprotein lipase and carnitine palmitoyltransferase 1, respectively) or overall fatty acid supply (dictated by events at the adipocyte) for fuel utilization by muscle during nutritional transitions. Finally, we assess the regulatory importance of glycogen synthesis in determining overall rates of glucose clearance by skeletal muscle during alimentary hyperglycemia and hyperinsulinemia.

Acetyl-CoA Carboxylase↗
PubMed1992

Glucose utilization and disposition by skeletal muscle during unrestricted feeding.

We measured glucose utilization index (GUI) values in individual skeletal muscles of conscious rats during the light (quiescent) and dark (feeding/activity) phases. There was a 2-3-fold variation in muscle GUI values, with peak values observed at the end of the dark phase and minimum values observed at 6-9 h into the light phase. GUI values in working muscles (soleus and adductor longus) were consistently higher than in non-working muscles (tibialis anterior and extensor digitorum longus), indicating that working muscles make the major contribution of the total skeletal muscle mass to glucose disposal during unrestricted feeding. There was a clear overall increase in muscle glycogen deposition during the first 9 h of the dark phase; this was concomitant with an increase in food consumption. Peak glycogen concentrations were reached after 9 h of darkness, but subsequently declined. The pattern of changes in muscle GUI values during the light and dark phases is discussed in relation to the role of insulin in facilitating glucose clearance.

Animals↗
PubMed1992

Variations in hepatic carbon flux during unrestricted feeding.

Previous findings have established a pivotal role for hepatic pyruvate dehydrogenase complex (PDH) in regulating hepatic carbon flux during the starved-to-fed and fed-to-starved nutritional transitions [Holness, McLennan, Palmer & Sugden (1988) Biochem. J. 252, 325-330; Holness & Sugden (1990) Biochem. J. 268, 77-81]. We have therefore examined liver PDH activities during the light and dark phases of the feeding cycle in the adult rat in relation to hepatic glycogenesis, fatty acid synthesis and cholesterogenesis. There was significant synchronous suppression of lipogenesis and glycogenesis during the light phase; rates were restored asynchronously during the dark (feeding) phase. Glycogen concentrations declined during the light phase and increased during the dark phase. Despite quite dramatic changes in rates of glycogen and lipid synthesis and hepatic glycogen concentrations during the light and dark phases, hepatic PDHa (active form) activity remained relatively unchanged. Qualitative and quantitative differences in the pattern of change in rates of synthesis of fatty acid and cholesterol suggested regulation at pathway-specific sites distal to PDH.

Animals↗
PubMed1990

Radiologic diagnosis of epiglottitis: objective criteria for all ages.

A retrospective study was undertaken to define objective radiologic parameters in diagnosing epiglottitis on soft-tissue lateral neck radiographic studies. Ratios of soft-tissue structures in 31 patients aged 7 months to 61 years with epiglottitis were compared with those of age- and sex-matched controls with croup, pharyngitis, and dysphagia. The ratios of epiglottic width to third cervical vertebral body width (EW/C3W) of more than 0.5, of aryepiglottic width to third cervical vertebral body width (AEW/C3W) of more than 0.35, and of epiglottic width to epiglottic height (EW/EH) of 0.6 or more were all found to be 100% sensitive and specific in differentiating between adult patients with and without epiglottitis. In children, EW/C3W, AEW/C3W, and EW/EH ratios of more than 0.5, of more than 0.35, and of 0.6 or more, respectively, were found to be 100% sensitive in detecting epiglottitis with specificities of 87%, 96%, and 87% respectively. These preliminary results suggest that EW/C3W, EW/EH, and AEW/C3W ratios of more than 0.5, of 0.6 or more, and of more than 0.35, respectively, may be useful in the radiologic diagnosis of epiglottitis in patients of all ages.

Adolescent↗
PubMed1990

Delayed brachial artery occlusion owing to a dog bite of the upper extremity.

We report a case of delayed presentation of vascular injury from a superficial dog bite of the upper extremity in a five-year-old male. This example of a significant arterial injury, in the setting of seemingly minor trauma, is the first known report of blunt arterial trauma owing to a dog bite in any age group. Blunt arterial trauma in children is rare unless associated with fractures, dislocations, or massive crush injuries. Additionally, persistent pulses following arterial occlusion are rare and can potentially lead to misdiagnosis of a serious arterial injury. A brief review of pediatric blunt vascular injuries is presented with implications for diagnosis and management of such cases.

Animals↗
PubMed1985

Advantages of a modified toluidine blue O stain and bronchoalveolar lavage for the diagnosis of Pneumocystis carinii pneumonia.

A modified toluidine blue O staining technique for Pneumocystis carinii is described. An easily prepared sulfation reagent made with sulfuric and acetic acids was used. The stain can be employed for bronchoalveolar lavages and lung tissue touch preparations. Most background material was removed by the sulfation reagent, slides were generally easy to read, and time from receipt of a specimen to reporting of results was approximately 1 h. P. carinii cysts were more easily visualized with this stain than in slides stained with modified methylene blue, Gram, Gram-Weigert, and standard toluidine blue O procedures. The importance of certain procedural aspects of subsegmental bronchoalveolar lavage, by which most of the specimens were obtained, is also emphasized.

Humans↗
PubMed1982

The effects of fatigue on the control of a coincident timing response.

The present study investigated the extent to which fatigue influenced the usage of feedback by Ss to make corrections during coincident timing responses. Sixteen college males watched a .01-sec timer and attempted to knock over a barrier at the moment that the sweep hand reached 500 msec. All Ss were given 50 trials of practice on each of four consecutive days. The fatigue group's performance was immediately preceded by a response-specific local fatigue (dynamic exercise). To insure the maintenance of a high level of fatigue throughout practice, the fatiguing exercise was interspersed with the coincident timing task. The control group performed the same exercise as the fatigue group but without any resistance. Schmidt's (1972) index of preprogramming (IP) was calculated for each day in order to determine the level of feedback involvement in controlling the movement. Fatigue did not influence the accuracy with which Ss responded or the rate that they learned. However, the results indicated a relatively high and stable IP throughout all trials with the IP for the fatigue group higher than that of the control, suggesting a preference by these Ss for a programming mode of control.

Adult↗