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H Baker

Publications and source records attributed to H Baker.

At least 109 records · Page 6Linked to original sources
PubMed1993

Adult naris closure profoundly reduces tyrosine hydroxylase expression in mouse olfactory bulb.

Peripheral afferent innervation appears to be required for the expression of the dopamine phenotype in the rodent main olfactory bulb. Experiments utilizing neonatal naris closure as a means of sensory deprivation also suggest that odor-induced afferent activity is required for the expression of the phenotype. These experiments are confounded, however, by the significant postnatal maturation of the dopamine system. The current experiments utilized adult unilateral naris closure to address this issue. As with neonatal closure, adult deprivation produces a profound reduction in the expression of tyrosine hydroxylase (TH), the first enzyme in the dopamine biosynthetic pathway. By 4 days a small decrease is observed in TH activity and immunoreactivity. Activity reaches a nadir of 12% of control levels at about 1 month. TH mRNA is reduced similarly when analyzed at about 2 months post-closure. Glutamic acid decarboxylase protein and mRNA expression, which are co-localized with TH, remain at close to control levels indicating the continued presence of the dopamine neurons. The time-course of the loss of TH is identical to that for zinc sulphate-induced denervation of the olfactory bulb. These data support the hypothesis that odor modulated afferent activity is required for expression of the dopamine phenotype and that, if a trophic factor is involved, its release is also activity dependent.

Animals↗
PubMed1993

Changes in activity and mRNA for rat tryptophan hydroxylase and aromatic L-amino acid decarboxylase of brain serotonergic cell bodies and terminals following neonatal 5,7-dihydroxytryptamine.

In the present study, we examined time-dependent changes in activity, mRNA and immunoreactivity of the serotonin biosynthetic enzymes, tryptophan hydroxylase (TPH) and aromatic L-amino acid decarboxylase (AADC) in dorsal raphe nucleus (DRN), caudal brainstem and hypothalamus, following intracisternal injection of 5,7-dihydroxytryptamine (5,7-DHT) in neonatal rats. TPH activity in central serotonergic cell bodies and terminals was reduced to 20-30% of control levels at 1-8 weeks after neonatal, low-dose 5,7-DHT injection (24 micrograms free base). In contrast, AADC activity was either not changed or decreased to 40% of control levels, depending on the region. In situ hybridization and immunocytochemical staining indicated that 5,7-DHT caused a marked reduction in TPH and AADC message levels as well as the number of 5-HT and AADC-immunoreactive cells within the DRN as early as 1 week after 5,7-DHT. Even 15 weeks after drug administration recovery did not occur. This apparent neuronal loss was region-specific suggesting that some serotonergic neurons are more resistant to neonatal 5,7-DHT treatment than others. Taken together, these studies indicate that neonatal treatment with 5,7-DHT produces a marked and permanent (up to 15 weeks) reduction in the number of central serotonergic neurons.

5,7-Dihydroxytryptamine↗
PubMed1993

Influence of dietary myoinositol on myocardial vulnerability and norepinephrine release in a diabetic animal model.

In a canine model of diabetes enhanced ventricular vulnerability (VFT) has been associated with reduced myocardial myoinositol and increased release of norepinephrine (NE). To assess the role of the polyol, a dietary supplement of myoinositol was fed for 1 year to a diabetic group. Diabetes was induced with alloxan, 30 mg/kg. Controls (Group 1) were compared with diabetics without (Group 2) and with the inositol supplement (Group 3). After 1 year the animals were anesthetized to assess VFT. Basal heart rate and arterial pressure were comparable. The VFT in Group 1 was 43 +/- 2.6 ma, 26.7 +/- 2.8 ma in Group 2 (P < 0.02) and 39 +/- 3.5 ma in Group 3 (P < 0.02 vs. Group 2). Since the cardiac sympathetic system may promote arrhythmogenesis, the release of NE into the coronary sinus (CS) has been determined. To assess basal NE release serial arterial (A) and (CS) samples were taken at 5 min intervals for 20 min during infusion of 3H-NE. There was no significant difference between the diabetic groups in the level of arterial NE (HPLC). The mean for NEA-CS was higher in Group 2 (-228 +/- 33 pg/ml) compared to normals (-75 +/- 19 P < 0.02). In Group 3 the mean NE in the coronary venous effluent was -33 +/- 9 pg/ml, significantly less than Group 2. Infusion of 3H-NE was attended by significantly higher 3H-NEcs levels in Group 2. While dihydroxyphenylglycol (DHPG) was increased, 3H DHPG was not, suggesting that an impaired uptake mechanism contributed to the increased NEcs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Axotomy-induced differential gene induction in neurons of the locus ceruleus and substantia nigra.

The biochemical and molecular events correlated with neuronal injury and survival are not well understood. Previous studies have reported that following axotomy, neurons in the substantia nigra pars compacta (SNc) and the locus ceruleus (LC) exhibit a significant increase in tyrosine hydroxylase (TH) enzyme activity within 24-72 h (Brain Res., 144 (1978) 325-342; Brain Res., 92 (1975) 57-72). To investigate the potential contribution of TH gene induction to this increase a semi-quantitative immunocytochemical and in situ hybridization time course analysis was undertaken. Following axotomy, TH immunoreactivity increased in neurons of both the SNc and LC. In contrast, an increase in TH mRNA was only evident in neurons of the LC. As a possible mechanism for the observed alterations in TH gene expression, the levels of an immediate early gene, c-fos, were examined. C-fos mRNA and Fos protein were not expressed in either normal or axotomized neurons of the SNc. However, the constitutive expression in control LC neurons increased significantly following axotomy. These data demonstrate the differential response of two central catecholaminergic populations to axotomy and suggests a potential role for the immediate early gene, c-fos, in the post-injury reaction.

Animals↗
PubMed1993

Olfactory afferent regulation of the dopamine phenotype in the fetal rat olfactory system.

Recent studies strongly suggest that functional olfactory receptor cell innervation is necessary for the maintenance of the dopamine phenotype in the adult rat olfactory bulb. To determine whether afferent innervation is required for the initial expression of the dopaminergic phenotype during development, the current studies investigated the association between afferent innervation and phenotypic expression using both in vivo and in vitro systems. Ontogeny of the dopamine phenotype in the rat main olfactory bulb was assessed by the appearance of immunoreactivity for tyrosine hydroxylase, the first enzyme in the dopamine biosynthetic pathway. Development of receptor afferent innervation of the bulb was demonstrated with olfactory marker protein immunoreactivity. Tyrosine hydroxylase-immunoreactive cells occurred only in regions of the olfactory bulb receiving afferent innervation. However, the appearance of afferent fibers in the olfactory bulb preceded tyrosine hydroxylase expression by three to four days (gestational days 14-15 versus 18, respectively). In explant cultures, significant numbers of tyrosine hydroxylase-containing cells were observed only in en bloc co-cultures of presumptive olfactory bulb and epithelium. Explant cultures of presumptive olfactory bulb alone contained few, if any, tyrosine hydroxylase-immunoreactive cells. Similarly, explants produced by recombining previously separated presumptive olfactory bulb and epithelium exhibited very few tyrosine hydroxylase-immunostained cells. These data suggest that expression of the dopamine phenotype, as indicated by the presence of tyrosine hydroxylase, depends on a critical level of afferent innervation. The results also support previous studies which indicated that neuronal activity or an activity-dependent process may be required for induction of tyrosine hydroxylase expression.

Animals↗
PubMed1993

A multicentre 12-week open study of a lipid-soluble folate antagonist, piritrexim in severe psoriasis.

An open, 12-week, multicentre study was conducted to assess the efficacy of piritrexim isethionate in the treatment of severe psoriasis. Piritrexim isethionate is a lipid-soluble dihydrofolate reductase inhibitor which cannot form polyglutamates, and may be as effective as methotrexate in the treatment of psoriasis. If, as is suspected, but as yet unproven, methotrexate polyglutamates are responsible for the hepatotoxicity of methotrexate, piritrexim should be less hepatotoxic, and may offer an alternative to methotrexate therapy. Fifty-five patients were enrolled, of whom 41 completed the study. Patients were allocated to receive either 150, 225, 300, or 450 mg of piritrexim weekly, in divided doses over 72 h (low-dose groups, 150 and 225 mg), or over 36 h (300 and 450 mg groups). Twenty-four of the 41 patients who completed the study had a greater than 50% improvement in the severity of their psoriasis, as demonstrated by a reduction in the Psoriasis Severity Score, a measure analogous to the PASI scoring system. Adverse events were common, but mild, and were controlled by dose reduction. Piritrexim appears to be an effective therapy for severe psoriasis at doses of 300 and 450 mg weekly, in three divided doses over 36 h.

Drug Administration Schedule↗
PubMed1993

Differential spatial and temporal gene expression in response to axotomy and deafferentation following transection of the medial forebrain bundle.

Alterations in the levels of neurotransmitter biosynthetic enzymes are a concomitant of many neurodegenerative disorders. In order to elucidate potential mechanisms for longterm alterations in biosynthetic enzyme gene products in response to neuronal injury, an acute axotomy/deafferentation model was employed. A unilateral microknife transection of the medial forebrain bundle (MFB) axotomizes and/or deafferents phenotypically identified neuronal populations important in the function of the basal ganglia. Semi-quantitative in situ hybridization and immunohistochemical analysis demonstrated that the products of the immediate-early gene c-fos were induced postaxotomy in the noradrenergic neurons of the locus ceruleus (LC), but not in the dopaminergic neurons of the substantia nigra pars compacta (SNc). Analysis of the levels of mRNA, protein, and activity for tyrosine hydroxylase demonstrated that the LC neurons survive the injury while the SNc neurons degenerate. After MFB transection, Fos protein also was induced in the corpus striatum within 1 hr, first in large, putatively cholinergic neuronal populations followed at 3 hr by the small, putatively GABAergic neurons. The substantia nigra pars reticulata and the subthalamic nucleus neuronal populations, deafferented by the MFB transection, also exhibited Fos induction beginning at 3 hr. The data suggest that expression of Fos in a neuronal population is correlative with respect to cell survival following either axotomy or deafferentation. Whether Fos induction following injury is either a necessary mechanism of cell survival or merely a marker of increased neuronal activity requires further investigation.

Animals↗
PubMed1993

Absorption and excretion of L-carnitine during single or multiple dosings in humans.

Changes of short-chain (free) and long-chain (acyl) carnitine activity (CA) in plasma, whole blood, red blood cells (rbc) and urine were induced (a) by ingestion of L-carnitine as a single dose of 500 mg, or 2500 mg, or (b) by ingestion of a daily dose of 2500 mg for 10 days. A single 500-mg dose induced insignificant increases of CA in blood constituents. However elevated free CA was noted in urine. Single or daily high doses--e.g. 2500 mg of carnitine--significantly increased free and acyl-CA in plasma, whole blood and urine, but these increases were low. Variations in dosage or frequency of carnitine intake led to no changes in rbc CA; presumably CA in plasma diffused only slowly into rbc. The apparent low absorption of carnitine suggests that oral therapy may not effect rapid repletion of body stores of CA.

Adult↗
PubMed1993

Tissue concentrations of water-soluble vitamins in normal and diabetic rats.

Changes in circulating and tissue concentrations of several vitamins have been reported in diabetic animals and human subjects. In this study, the effect of short-term (2 weeks) streptozotocin diabetes on folate, B6, B12, thiamin, nicotinate, pantothenate, riboflavin and biotin in liver, kidney, pancreas, heart, brain and skeletal muscle of rats was investigated. The tissue distribution of vitamins varied widely in normal rats. Diabetes significantly lowered folate in kidney, heart, brain, and muscle; B6 in brain; B12 in heart; thiamin in liver and heart; nicotinate in liver, kidney, heart and brain; pantothenate in all tissues; riboflavin in liver, kidney, heart, and muscle. These results indicate that experimental diabetes causes a depression of several water-soluble vitamins in various tissues of rats.

Animals↗
PubMed1992

Dopa-decarboxylation in the striata of rats with unilateral substantia nigra lesions.

The source and site of the DOPA decarboxylation to dopamine in Parkinson's disease (PD) and animal models of PD are controversial. Since most of aromatic L-amino acid decarboxylase (AADC) are lost along with the degenerating dopaminergic neurons, we addressed the possibility that other decarboxylases or a novel protein that is structurally different from AADC decarboxylate L-DOPA in the denervated striatum. Immunotitration of the extracts from the denervated striatum with AADC antibody showed that all activity can be attributed to AADC-immunoreactive protein. We then investigated if there are non-dopaminergic intrinsic striatal neurons that express AADC. No evidence of such neurons was noted by immunocytochemistry and in situ hybridization.

Animals↗
PubMed1992

Region-specific expression of a K+ channel gene in brain.

Northern blot analysis and in situ hybridization studies reveal the highly localized expression in rat brain of transcripts from a gene (KShIIIA) encoding components for voltage-gated K+ channels. KShIIIA expression is particularly prominent throughout the dorsal thalamus. The expression of KShIIIA is compared to that of a closely related gene, here called NGK2-KV4. These two genes encode transcripts that induce currents in Xenopus oocytes that are as of yet indistinguishable, but they show very different patterns of expression in rat brain. NGK2-KV4 transcripts are particularly abundant in the cerebellar cortex, where KShIIIA expression is very weak. These results demonstrate the existence of cell-type-specific K+ channel components and suggest that one reason for the unusually large diversity of K+ channel proteins is the presence of subtypes that participate in specific brain functions.

Amino Acid Sequence↗
PubMed1992

Effect of cyclosporine treatment on carnitine and myo-inositol in diabetic rats.

1. The effect of long-term (20 wk) treatment of cyclosporine A (CyA) was studied in urine, blood, liver, kidney and pancreatic concentrations of acid-soluble carnitine and free myo-inositol in streptozotocin diabetic rats. 2. Diabetic rats excreted significantly higher concentrations of carnitine and myo-inositol; CyA prevented the urinary loss of carnitine but not myo-inositol. 3. Blood carnitine levels were not different between normal and diabetic rats, however, CyA significantly decreased these levels. Conversely, blood myo-inositol concentrations were higher in diabetic than in normal rats; CyA prevented this increase. 4. Hepatic concentrations of both carnitine and myo-inositol were increased in diabetic rats; CyA treatment caused even further increase. 5. Pancreas from diabetic rats contained less carnitine and myo-inositol compared to normal pancreas. CyA treatment did not affect pancreatic carnitine, but it normalized myo-inositol in diabetic rats. 6. The kidney carnitine or myo-inositol levels were not influenced either by diabetes or by CyA treatment. 7. These results suggest that CyA treatment causes changes in carnitine and myo-inositol concentrations in biologic fluids and certain tissues.

Animals↗
PubMed1992

Effect of interleukin-2 on some micronutrients during adoptive immunotherapy for various cancers.

In 20 patients, we investigated the effect of interleukin-2 (IL-2) treatment during adoptive immunotherapy for various cancers on circulating levels of: thiamin; biotin; folate; pantothenate; riboflavin; nicotinate; vitamins A, B6, B12 and E; carotenes; free and total cholines; inositol; and free and total carnitines. Of the above micronutrients, only vitamins A, B6, B12, inositol, carotenes and folate varied markedly from normal levels (pre IL-2 exposure) to abnormal levels (post IL-2). Following IL-2 exposure, every patient's B12 level was significantly elevated; 50% of the levels were abnormally increased above 1000 pg/ml. Extreme significant elevations of inositol were also seen in 90% of the patients. In contrast, IL-2 exposure depressed normal vitamins A, B6, carotene, and folate levels to subnormal; 90% of the patients became B6 hypovitaminemic; 60% for vitamin A, 80% for carotene, and 45% for folate. Other micronutrients tested showed no clear deviations from normal levels post IL-2 exposure. Some reasons for micronutrient variations are discussed.

Adult↗
PubMed1992

Inherited prion disease with 144 base pair gene insertion. 2. Clinical and pathological features.

A large family with autosomal dominant segregation of presenile dementia, and other neurological and behavioural features is described. At various times, family members have carried diagnoses of Alzheimer's disease, Huntington's disease, Parkinson's disease, myoclonic epilepsy, atypical dementia, Pick's disease, Creutzfeldt-Jakob disease and Gerstmann-Sträussler syndrome. Molecular genetic studies have enabled classification of this disease at the molecular level as one of the group of inherited prion diseases. Here we describe the phenotype of inherited prion disease (PrP 144 bp insertion).

Adult↗
PubMed1992

A comparison of quality of care using Phaneuf's Nursing Audit.

The quality of nursing care delivered to two groups of patients suffering from diabetes mellitus was examined. Using Phaneuf's Nursing Audit, a retrospective audit of the nursing documentation regarding the care of all patients was carried out, and a comparison made of the numeric scores obtained. The nursing care of the group of patients from the Professional Nursing Unit (PNU) obtained mean scores which were 26.4% higher than those obtained by the group from the general hospital wards. There are major variations in scores in specific areas. These give rise to some questions regarding the value to nurses of the caring and nurturing component of nursing work, and how this is affected by differing philosophies and environments.

Adolescent↗
PubMed1992

A jejunoileal bypass rat model for rapid study of the effects of vitamin malabsorption.

Jejunoileal bypass operation was originally done to promote weight loss for treatment of morbid obesity. We used such a model to determine if dietary vitamin absorption is compromised by such an operation. Six rats were subjected to a jejunoileal bypass, 6 control rats were pair-fed to bypassed rats; and 6 were fed ad libitum. Vitamin content of folic, B6, riboflavin, nicotinate, pantothenate, thiamin, biotin, B12, vitamins A, E, and carotene in blood and liver was determined after 8 postoperative weeks. Aside from riboflavin, blood vitamin levels were significantly depressed in bypassed rats. The deepest depression was seen for B12, carotene and vitamin E. Liver vitamin stores of folate, riboflavin, thiamin, B12, clearly were significantly depressed in the bypassed animals compared to the pair-fed and ad libitum-fed controls. This model can serve for rapidly studying micronutrient depletion due to malabsorption without dietary manipulation or antibiotics for gut sterilization.

Animals↗
PubMed1991

Differential effect of functional olfactory bulb deafferentation on tyrosine hydroxylase and glutamic acid decarboxylase messenger RNA levels in rodent juxtaglomerular neurons.

Expression of the dopaminergic phenotype in olfactory bulb (OB) juxtaglomerular neurons (constituting a population of periglomerular and external tufted cells) is dependent upon functional innervation by peripheral olfactory receptors. Loss of functional input in rodents, by either peripheral deafferentation or deprivation of odorant access, results in a profound decrease in the expression of juxtaglomerular tyrosine hydroxylase (TH). We have examined the effects of such treatments on the expression of the neurotransmitter biosynthetic enzyme glutamic acid decarboxylase (GAD), which is colocalized with TH in the majority of TH-containing juxtaglomerular neurons. Following either chemically induced OB deafferentation in adult mice or unilateral odor deprivation in neonatal rats, steady-state OB GAD messenger RNA levels remained essentially unchanged as assessed by Northern blot analysis 20-40 days after treatment. These results were confirmed by in situ hybridization analysis, which demonstrated a profound loss of juxtaglomerular TH messenger RNA but no accompanying decrease in regionally colocalized GAD message. Since GAD is found in nearly all dopaminergic OB cells, the preservation of juxtaglomerular GAD message implies that olfactory receptor neurons exert a differential transneuronal regulation of TH and GAD gene transcription.

Animals↗