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Biomedical subjects

E Walters

Publications and source records attributed to E Walters.

At least 19 recordsLinked to original sources
PubMed2003

Fatty acid abnormalities in chronic pancreatitis: effect of concomitant diabetes mellitus.

OBJECTIVE: Patients with chronic pancreatitis suffer from malabsorption and nutritional deficiencies. However there is little data available concerning the fatty acid profile in chronic pancreatitis. Diabetes mellitus, a common complication of this disease, could interfere with the metabolism of fatty acids. SUBJECTS: We therefore compared the fatty acid composition of LDL from four groups of male patients with (a) chronic pancreatitis without diabetes (ND-CP; n=12), (b) diabetes secondary to chronic pancreatitis and insulin-treated (CP-D; n=35); (c) type 1 diabetes (n=25); and (d) controls (n=20). RESULTS: The patients in both groups of chronic pancreatitis (ND-CP and CP-D) had lower mean values for linoleic acid than that seen in the type 1 DM and control groups, whereas monounsaturated fatty acids (MUFA; 18 : 1(n-9) and (16 : 1(n-7)) were significantly increased in these two groups (ND-CP and CP-D). Docosa-hexaenoic-acid (22 : 6(n-3)) was significantly decreased in the CP-D group (P>0.05), a response that could be explained by the effects of diabetes mellitus and by selenium deficiency. In this way, diabetes was associated with a decrease in the docosa-hexaenoic-acid (22 : 6(n-3); r=0.30, P=0.005), and selenium was correlated with DHA (r=0.28, P=0.029) and with the 22 : 6(n-3)/20 : 5(n-3) ratio (evaluating the delta 4 desaturation); r=0.31, P=0.022), independently of the diabetes effect. Selenium was negatively correlated with 20 : 4(n-6)/20 : 3(n-6) ratio (evaluating the delta 5 desaturase; r=-0.30; P=0.025). These results suggest that these two factors may have a role in the regulation of the desaturation process. If we consider that a ratio of 16 : 1(n-7)/18 : 2(n-6) greater than 0.086 in plasma indicates an EFAn-6 deficiency, 40% of our CP patients, 57.6% of CP-D patients and 13.6% of type 1 DM patients were involved. CONCLUSIONS: The consequences of these deficiencies are not evaluated in this disease. However, correction of the fundamental deficiencies in essential fatty acids and in selenium seems desirable in chronic pancreatitis.

Adult↗
PubMed2002

Microfluidic technology for assisted reproduction.

The physical tools used in assisted reproduction have changed little over several decades. Microfluidics is an emerging technology that allows a fresh examination of the way assisted reproduction is performed. Here we review our work to develop microfluidic devices to perform the functions required in assisted reproduction. These functions include loading/unloading, culture, chemical manipulation, and mechanical manipulation of embryos and oocytes. Basic microfluidic theory and microfluidic device design and operation are discussed. Results are presented for mechanical removal of cumulus cells and for embryo culture. Results suggest that microfluidic systems will lead to improved efficiencies in assisted reproduction.

Animals↗
PubMed2002

Deficiencies of micronutrients, altered bowel function, and quality of life during late follow-up after pancreaticoduodenectomy for malignancy.

BACKGROUND/AIM: A previous study in our unit showed an inadequate dietary intake of fat-soluble vitamins and energy after pancreaticoduodenectomy (PD). This study was designed to determine whether deficiencies in dietary intake of micronutrients lead to nutritional deficiencies and to examine the impact of dietary advice on nutrition, bowel function, and quality of life. METHODS: Ten patients who had undergone PD for malignant disease more than 6 months previously were studied at baseline and follow-up 8 weeks apart. Dietary intakes of energy, fat, and micronutrients were assessed by analysis of weighed food diaries, and serum vitamins and trace elements were measured at each visit. Quality of life questionnaires (EORTC QLQ30 and PAN 26) were answered, and a clinical assessment of the bowel function was made. Targeted dietary intervention was given, where indicated, and its impact on the study parameters was assessed at the second clinic visit. RESULTS: The patients were generally well nourished. Dietary deficiencies of fat-soluble vitamins were detected (vitamin A, n = 2; vitamin D, n = 10; vitamin E, n = 2), but these correlated with serum deficiency only for vitamin A. The selenium intake was borderline or insufficient in 6 patients' diet, with serum deficiencies in 4. Despite normal intakes of iron and zinc, half the patients showed serum deficiency. The bowel function was an important factor in quality of life, and symptoms improved in 3 patients with enzyme supplements and antidiarrhoeal medication. CONCLUSIONS: PD patients appear to be prone to a predictable set of micronutrient deficiencies that may be compounded by insufficient dietary intake. The bowel function is important to these patients, and it should be optimized with aggressive enzyme replacement. Dietary intervention appears to make little short-term impact in the areas studied.

Aged↗
PubMed2001

The OMP-lacZ transgene mimics the unusual expression pattern of OR-Z6, a new odorant receptor gene on mouse chromosome 6: implication for locus-dependent gene expression.

Reporter gene expression in the olfactory epithelium of H-lacZ6 transgenic mice mimics the cell-selective expression pattern known for some odorant receptor genes. The transgene construct in these mice consists of the lacZ coding region, driven by the proximal olfactory marker protein (OMP) gene promoter, and shows expression in a zonally confined subpopulation of olfactory neurons. To address mechanisms underlying the odorant receptor-like expression pattern of the lacZ construct, we analyzed the transgene-flanking region and identified OR-Z6, the first cloned odorant receptor gene that maps to mouse chromosome 6. OR-Z6 bears the highest sequence similarity (85%) to a human odorant receptor gene at the syntenic location on human chromosome 7. We analyzed the expression pattern of OR-Z6 in olfactory tissues of H-lacZ6 mice and show that it bears strong similarities to that mapped for beta-galactosidase. Expression of both genes in olfactory neurons is primarily restricted to the same medial subregion of the olfactory epithelium. Axons from both neuronal subpopulations project to the same ventromedial aspect of the anterior olfactory bulbs. Furthermore, colocalization analyses in H-lacZ6 mice demonstrate that OR-Z6-reactive glomeruli receive axonal input from lacZ-positive neurons as well. These results suggest that the expression of both genes is coordinated and that transgene expression in H-lacZ6 mice is regulated by locus-dependent mechanisms.

Animals↗
PubMed2001

Effect of the inflammation, chronic hyperglycemia, or malabsorption on the apolipoprotein A-IV concentration in type 1 diabetes mellitus and in diabetes secondary to chronic pancreatitis.

The metabolism of apolipoprotein (apo) A-IV in diabetes mellitus (DM) is poorly understood. Several factors, such as dietary fat intake, fat malabsorption, acute inflammation, and hormonal dysregulation can disturb the plasma apo A-IV concentration. We have compared the plasma apo A-IV concentrations in patients with type 1 DM and DM secondary to chronic pancreatitis to determine the effects of combinations of these factors. We examined 4 groups of male patients with chronic pancreatitis without diabetes (ND-CP) (n = 12), diabetes secondary to chronic pancreatitis and insulin-treated (CP-DM) (n = 32), type 1 diabetes (n = 25), and controls (n = 20). Plasma apo A-IV was significantly lower in the chronic pancreatitis patients (ND-CP and CP-DM) than in the other patients. Inflammatory proteins (fibrinogen, ceruloplasmin, and haptoglobin) were significantly elevated in the 2 chronic pancreatitis groups. The apo A-IV concentration was positively correlated with hemoglobin A(1c) (HbA(1c)) percentage in each group of diabetic patients (CP-DM, r =.35; P =.046; type 1 DM, r =.53; P =.010), in both groups of diabetic patients (r =.472; P <.0001) and negatively correlated with ceruloplasmin concentration in each group of diabetic patients (CP-DM, r = -.48; P =.0052; type 1 DM, r = -.66; P =.003), in both groups of diabetic patients (r = -.561; P <.0001), and in the whole population (r = -.463; P <.0001). Apo A-IV was also negatively correlated with haptoglobin in type 1 DM patients (r = -.434; P =.0435), in the both groups of diabetic patients (r = -.349; P =.0154), and in the whole population (r = -.351; P =.0019). Multiple linear regression analysis revealed that only HbA(1c) and ceruloplasmin were independent explanatory variables. Plasma apo A-IV is positively correlated with HbA(1c) suggesting that hyperglycemia per se selectively affects apo A-IV metabolism. The correlation between the concentrations of inflammatory protein and apo A-IV suggest a link between chronic inflammation and apo A-IV synthesis or catabolism. As apo A-IV is involved in reverse cholesterol transport, its low level in CP-DM may contribute to the accelerated development of atherosclerosis in these patients.

Adult↗
PubMed2001

Potential dangers in the customary methods of conducting meta-analyses. Recombinant versus urinary follicle stimulating hormone.

The customary method of combining success rates in meta-analyses may often result in serious biases, leading to erroneous inferences. This arises because of an inadmissible pooling of frequencies from heterogeneous sources. The fundamental statistical principle, that the magnitude of an 'effect' should always be tested against the variation in that effect over the sample, may not therefore be satisfied. A simple, but rigorous, alternative method is described.

Bias↗
PubMed1998

Does olfactory marker protein participate in olfactory neurogenesis?

Olfactory marker protein (OMP) is a phylogenetically conserved, 19-kDa, acidic, soluble protein found abundantly in mature olfactory sensory neurons. Its function has been enigmatic although recent evidence from studies on OMP null mice suggests that neurons lacking OMP exhibit altered physiological activity, including prolonged onset and recovery kinetics following stimulation. We have reported increased expression of OMP in individual surviving sensory neurons that have been deprived of their target, the olfactory bulb. Because olfactory epithelia deprived of their target also exhibit an increased rate of cell division we investigated the effect of recombinant OMP on cell division in organotypic cultures of fetal rat (embryonic day 19) epithelium grown for 3 days in vitro. After 3 days, cultures were given a 1-hr pulse of a mitotic marker, bromodeoxyuridine (BrdU), fixed and prepared for immunohistochemistry to determine the number of proliferating cells. We found a dose-dependent increase in the number of BrdU-positive cells/100-mm length of epithelium. The number of labeled cells increased incrementally, reached a plateau at 25 pM OMP/ml culture medium, 50% higher than in cultures with no OMP added, and remained at that level at 50 and 100 pM doses. Controls included trypsinized OMP and addition of equivalent volumes of TRIS buffer lacking OMP. These results, taken together with previous studies on several growth factors indicate that regulation of neurogenesis in olfactory tissue is a multifactorial process and that OMP may play a role.

Animals↗
PubMed1998

Effects of mutation of the Olf-1 motif on transgene expression in olfactory receptor neurons.

We have examined the effect of mutating the Olf-1 binding motif of the olfactory marker protein (OMP) promoter in determining olfactory neuron-specific gene expression in adult tissues and during embryonic development. The proximal Olf-1 motif located 170 nucleotides upstream of the transcription start site of the OMP gene was mutated to prevent its interaction with the Olf-1 factor in vitro. The wild-type and mutated fragments of the OMP gene extending from -239 to +55 nucleotides relative to the transcription start site were used to direct expression of a lacZ reporter gene in transgenic mice. The transgenic animals were analyzed for cell-specific and developmental expression of the reporter gene. We demonstrate that the mutation that prevents interaction of Olf-1 with its binding site does not alter the temporal and spatial patterns of gene expression in olfactory sensory neurons but does alter the specificity and level of expression in other neuronal populations. These observations are consistent with our demonstration that the mutated Olf-1 site interacts with nuclear proteins present in the central nervous system (CNS).

Animals↗
PubMed1998

Prenatal differentiation of mouse vomeronasal neurones.

The vomeronasal organ (VNO) subserves basic chemosensory functions in rodents, mainly related to sexual behaviour. In order to understand early stages of the VNO structural maturation, we have undertaken an immunocytochemical analysis of the VNO of fetal mice. Our results demonstrate that Olfactory Marker Protein (OMP), a marker of differentiated chemosensory cells, is already expressed in vomeronasal neurones and their fibres projecting to the accessory olfactory bulb during the last week of gestation. However, in contrast to the adult, where its expression is restricted to the medial sensory neuronal component of the VNO, during fetal development OMP is also present in cells located in the lateral non-sensory epithelial component. Some other markers of nasal chemosensory neurones, such as GAP-43/B-50, Protein Gene Product 9.5 (PGP 9.5) and carnosine are also transiently expressed in this ectopic site. These results indicate that (i) significant morphological and biochemical maturation of the VNO is achieved before birth; (ii) transient cell populations, sharing the biochemical profile of the vomeronasal chemosensory receptors, occur in ectopic areas during fetal development.

Animals↗
PubMed1998

An enhanced olfactory marker protein immunoreactivity in individual olfactory receptor neurons following olfactory bulbectomy may be related to increased neurogenesis.

Olfactory marker protein (OMP) is a 19-kD acidic protein found throughout the cytoplasm of mature olfactory receptor neurons (ORNs). Its function remains unknown. Following olfactory bulbectomy, the proportion of ORNs mature enough to express OMP declines greatly. However, in the few remaining mature ORNs, it has been observed that the intensity of OMP immunoreactivity (IR) appears to increase over that of ORNs on the unoperated side. We have now investigated this phenomenon quantitatively in rats subjected to unilateral olfactory bulbectomy. Results show that at all postbulbectomy survival periods examined quantitatively (3 days to 6 months), a significant decrease (19-37%) occurs in the transmission of incident light through OMP(+)-ORNs in bulbectomized versus unoperated olfactory epithelium (OE). Further, we also observed a consistent side-to-side difference in OMP IR in control unoperated animals. Possible explanations for these observations and their relation to the still unknown function of OMP are discussed. To test the possibility that OMP might serve a mitogenic role in the OE, recombinant OMP was added to organotypic explant cultures of fetal olfactory mucosa. Addition of OMP resulted in a dose-dependent increase in the density of bromodeoxyuridine-positive cells in the cultures, with a 50% increase occurring at the plateau OMP concentration of 25 pM.

Amino Acid Sequence↗
PubMed1996

Olfactory glomeruli are innervated by more than one distinct subset of primary sensory olfactory neurons in mice.

The rodent olfactory epithelium consists of a mosaic of primary sensory olfactory neurons (PONs) which express distinct putative olfactory receptor proteins. Recent evidence suggests that individual subsets of these sensory neurons project to separate glomeruli in the olfactory bulb (Vassar et al., [1994] Cell 79:981-991). In the present study we have identified two distinct subsets of primary sensory olfactory neurons (PONs) in the H-OMP-LacZ-6 transgenic mouse. In these transgenic mice, a LacZ reporter gene under the control of a 294 base pair element from the 5' promoter region of the olfactory marker protein (OMP) gene was expressed in a subset of PONs located in a discrete band of neuroepithelium in the nasal cavity. These LacZ positive neurons were not randomly located within this band but were more concentrated within a locus between endoturbinates IIb and III. The axons of these neurons densely innervated three adjacent and bilaterally symmetrical glomeruli present in the ventromedial olfactory bulb. Labeling of tissue sections with the plant lectin Dolichos biflorus (DBA) revealed an independent subset of PONs in the transgenic mice. These neurons were present in a wide region of the nasal cavity that included the neuroepithelial band containing the LacZ expressing neurons. The DBA labeled axons terminated in glomeruli in the rostromedial and dorsolateral olfactory bulb surfaces. Although the glomeruli innervated by the LacZ and DBA positive axons were predominantly non-overlapping there were glomeruli in the ventral olfactory bulb that were labeled by both DBA and LacZ markers. Eight different types of glomeruli were characterized. Most notably, glomeruli were identified which were innervated partially by both or by either subset alone. In these cases, axon subsets were observed to terminate within discrete subregions of a glomerulus. These results support the hypothesis that phenotypically distinct subsets of PONs converge on to the same glomeruli but also indicate that some glomeruli are innervated by more than one subset of sensory neuron. These findings have implications for understanding how the olfactory projection is formed and how olfactory information is processed.

Animals↗
PubMed1996

Proximal regions of the olfactory marker protein gene promoter direct olfactory neuron-specific expression in transgenic mice.

Olfactory marker protein (OMP) expression is highly restricted to mature olfactory neurons (ON). Less than 0.3 kb of upstream 5' flanking sequence of the OMP gene directs lacZ expression preferentially to ON in several independently derived lines of transgenic mice. A larger transgene with 0.8 kb of upstream flanking sequence also gave lacZ expression in ON and in a few ectopic sites in the central nervous system (CNS). In addition to the main olfactory epithelium, endogenous OMP is also expressed in chemosensory neurons of the vomeronasal and septal organs, and lacZ expression was detected in neurons of these sites as well. This confirmed the presence of regulatory sequences in the proximal portion of the OMP gene. Endogenous OMP expression in ON was normal in all transgenic lines. Strikingly, in several transgenic lines lacZ expression was restricted to subsets of ON. In one such line, ON axons were intensely stained for lacZ and projected to a subset of olfactory bulb glomeruli. Although identifiable subsets of ON and their termination fields have been described previously, this is the first demonstration of this phenomenon in transgenic mice. These lines of transgenic mice thus provide in vivo models for characterization of genetic elements regulating developmental and functional organization of the olfactory neuroepithelium.

Animals↗
PubMed1996

LacZ and OMP are co-expressed during ontogeny and regeneration in olfactory receptor neurons of OMP promoter-lacZ transgenic mice.

The ontogeny and cellular specificity of expression of beta-galactosidase activity and olfactory marker protein (OMP) are compared in olfactory tissue of the H-OMP-lacZ-3 line of transgenic mice. In this line the expression of lacZ is driven by a 0.3 kb fragment of the rat OMP promoter. During fetal development, lacZ expression is detectable in olfactory receptor neurons (ORNs) shortly after the initial appearance of endogenous OMP. The beta-galactosidase marker was observed only in mature olfactory receptor neurons where it co-localized with endogenous OMP. It was absent from immature neurons that express the growth associated phosphoprotein B50/GAP43. Lesion of the peripheral olfactory pathway by intranasal irrigation with Triton X-100 eliminated expression of both OMP and lacZ in the olfactory neuroepithelium. Subsequent regeneration of the full complement of olfactory receptor neurons was associated with co-expression of both OMP and beta-galactosidase activity. Neither OMP nor beta-galactosidase activity was induced in any other cell type of the regenerating olfactory mucosa. Thus, as little as 0.3 kb of the OMP promoter has the ability to target lacZ expression to olfactory receptor neurons in a temporally and spatially defined manner. We discuss the potential utility of this transgenic line for future studies of the olfactory system.

Animals↗
PubMed1995

Mechanism of neuroinvasion of Venezuelan equine encephalitis virus in the mouse.

Venezuelan equine encephalitis virus (VEE) causes a biphasic disease in mice following subcutaneous inoculation in the footpad. In the initial phase, virus replicates primarily in the lymphoid tissues and induces a high titer viremia. Subsequently, the virus invades the central nervous system (CNS) from the circulation, and an encephalitis ensues. At the earliest times that VEE specific in situ hybridization signal was observed in the CNS, it was in areas of the brain involved in olfaction, leading to the hypothesis that virus may invade the brain from the circulation through the olfactory system. The results presented in this paper define the route of CNS invasion in experimental murine VEE disease initiated by subcutaneous inoculation. Virus circulating in the blood appears to seed specific areas of the peripheral nervous system during the viremic lymphoid phase of the illness. Virus replication within olfactory and dental tissues is followed by centripetal spread of virus along neural pathways. Virus enters the brain in a pattern reflecting the proximity of the peripheral invasion site to the CNS. Specifically, virus is first found in the brain within the structures of the olfactory system, followed by areas innervated by the trigeminal nerve. Virus later disseminates along fiber tracts and connected circuits within the brain, resulting in a disseminated meningoencephalitis. Surgical or chemical interruption of the olfactory system at the level of the olfactory neuroepithelium or the main olfactory bulb inhibited entry of VEE into the CNS through the olfactory nerve. However, the olfactory route is not absolutely required for CNS invasion, as virus invaded the CNS of olfactory ablated animals through the trigeminal nerve. These observations are consistent with a model of hematogenous seeding of the peripheral nervous system, followed by invasion of the CNS by direct neural spread.

Animals↗
PubMed1994

Depression and parental bonding: cause, consequence, or genetic covariance?

It is shown how information on the direction of causation between variables may be obtained from a cross-sectional study of pairs of relatives. This method is applied to the study of the relationship between ratings of parents' rearing style and depression in their offspring. Adult female twins ascertained from a population-based registry in Viroffia completed the Center for Epidemiological Studies--Depression Scale (CESD) and a 7-item short form of the Parental Bonding Instrument (PBI) about each of their parents. Two dimensions of parental behavior, overprotectiveness and coldness, were analyzed jointly with depression data in both genetic factor and directional genetic models. Models that specify ratings of parents as a cause of depression in the offspring fit the data significantly better than models that specify depression as a cause of ratings of parents. A still better fit is obtained with models that specify common genetic variance to depression and ratings, though causal models with error variance perform almost as well. In general, ratings of fathers show more genetic and less shared environmental variance than ratings of mothers, which might arise from more consistent treatment of offspring by mothers than by fathers. No effect of children eliciting parental rearing style was detected with these data. The relative merits of instrumental variable, longitudinal, and family approaches to testing causal models are discussed.

Adult↗
PubMed1993

Olfactory cytochrome P-450 immunoreactivity in mice is altered by dichlobenil but preserved by metyrapone.

Antibodies to cytochromes P-450NMa and P-450NMb (CYP2A and CYP2G1, respectively) (P-450 nomenclature by Nebert et al., DNA Cell Biol. 10, 1- (1-14) 14, 1991) were used to assess the effects of the herbicide dichlobenil on the distribution of these olfactory-specific isozymes in the olfactory mucosa. Twenty-eight hours after a single dose (12 mg/kg) of dichlobenil, characteristic regions of the olfactory mucosa showed signs of necrosis in H&E stained sections. Accompanying this was a dramatic reduction in P-450 immunoreactivity in Bowman's glands of the olfactory mucosa, and an apparent redistribution of P-450 immunoreactivity within sustentacular cells. Treatment of mice with metyrapone, a P-450 inhibitor, at 10 min prior to and 2, 4, 6, and 8 h after a single dichlobenil injection, provided some protection against the damaging effects of dichlobenil. Both the gross and subcellular appearance of P-450 immunoreactivity in metyrapone/dichlobenil treated mice was similar to controls. Western blot analysis of P-450 expression following dichlobenil or metyrapone/dichlobenil treatment was generally consistent with immunohistochemical findings. These studies support previous reports that dichlobenil-induced olfactotoxicity is cytochrome P-450 mediated.

Animals↗