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Biomedical subjects

J W Hamilton

Publications and source records attributed to J W Hamilton.

At least 19 recordsLinked to original sources
PubMed1996

The diving reflex in non-eosinophilic non-allergic rhinitis.

The usual nasal response to head submersion in aquatic mammals is an increase in resistance to airflow, the so-called diving reflex. Although less well developed in humans, it is nevertheless present. It is likely to occur due to a relative increase of parasympathetic over sympathetic control of the nasal vasculature. Non-eosinophilic non-allergic rhinitis is thought to be due to a similar imbalance and we have attempted to establish whether the diving reflex is abnormal in this condition. Sixteen normal subjects and 18 subjects with non-eosinophilic non-allergic rhinitis (NENAR) underwent simulated diving using the "cold face test'. Expiratory total nasal airway resistance (ETR) was measured before and after the test by means of active anterior rhinomanometry. There was no significant increase in ETR in the normal group but a significant increase in ETR in the NENAR group (pre-test median ETR-0.464 kPa.s.l(-1). post-test median ETR 0.667 kPa.s.l(-1), (Wilcoxon's signed rank test P < 0.05). The change in median ETR in the NENAR group was also significantly higher than the median change in ETR in the normal group (Mann-Whitney, extract probability P = 0.04). We conclude the nasal airway response to simulated diving in NENAR is abnormal.

Airway Resistance↗
PubMed1996

The effect of intranasal fluticasone propionate on the diving reflex in patients with non-eosinophilic non-allergic rhinitis.

The usual nasal response to head submersion in aquatic mammals is an increase in resistance to airflow, the so-called "diving reflex". Although less well-developed in humans, it is nevertheless present. It is likely to occur due to a relative increase of parasympathetic over sympathetic control of the nasal vasculature. Non-eosinophilic non-allergic rhinitis is thought to be due to a similar imbalance and we have attempted to establish whether the diving reflex is abnormal in this condition and whether intranasal fluticasone propionate for 6 weeks has any effect in modifying the nasal response.

Administration, Intranasal↗
PubMed1996

Free revascularized jejunal loop repair following total pharyngolaryngectomy for carcinoma of the hypopharynx: report of 90 patients.

Ninety patients with carcinoma of the hypopharynx underwent pharyngolaryngectomy and reconstruction with a jejunal free autograft. Fifty-five patients had primary surgery and 35 salvage surgery for recurrence after radiotherapy. Following primary surgery 28 patients had postoperative radiotherapy and 27 did not. Complications occurred in 51 per cent of patients, the most common being necrosis of the jejunal graft (19 per cent); 12 per cent developed significant stenosis and 4 per cent died in the perioperative period. Eleven per cent of patients developed a fistula. The total number of complications diminished as the experience of the unit increased. Median follow-up was 4.9 years. Of patients treated with primary surgery, 48 per cent developed primary site recurrence (at 3 years) and 53 per cent neck node recurrence (at 5 years). The tumour-specific 5-year survival rate for all patients was 42 per cent. Following primary surgery 28 per cent survived for 5 years and after salvage surgery the rate was 59 per cent. Positive resection margins and extensive neck disease adversely affected survival (P = 0.02 and P = 0.001 respectively). The free revascularized jejunal graft is a safe and predictable method of repair following total pharyngolaryngectomy.

Adult↗
PubMed1995

Preferential effects of the chemotherapeutic DNA crosslinking agent mitomycin C on inducible gene expression in vivo.

The immediate effects of a single dose of the chemotherapeutic DNA crosslinking agent, mitomycin C (MMC), on the expression of several constitutive and drug-inducible genes were examined in a simple in vivo system, the 14 day chick embryo. We observed no effect of MMC on the steady-state mRNA expression of the constitutively expressed beta-actin, transferrin, or albumin genes. In contrast, MMC treatment significantly altered both the basal and drug-inducible mRNA expression of two glutethimide-inducible genes, 5-aminolevulinic acid (ALA) synthase and cytochrome P450 CYP2H1. The basal expression of these genes was transiently but significantly increased over a 24 hr period following a single dose of MMC. Conversely, MMC significantly suppressed the glutethimide-inducible expression of these genes when administered 1 to 24 hr prior to the inducing drug. The effects of MMC on both basal and drug-inducible ALA synthase and CYP2H1 mRNA expression were principally a result of changes in the transcription rates of these genes. In contrast, MMC treatment had little or no effect on glutethimide-induced expression of ALA synthase or CYP2H1 when administered 1 hr after the inducing drug, suggesting that a very early event in the induction process represents the target for these MMC effects. Covalent binding studies demonstrated that the effects of MMC on gene expression were closely correlated temporally with formation of [3H]-porfiromycin-DNA adducts. These results support the hypothesis that genotoxic chemicals specifically target their effects to inducible genes in vivo.

5-Aminolevulinate Synthetase↗
PubMed1995

Peter Shaffer's Amadeus as a further expression of twinship conflict.

In Peter Shaffer's Amadeus, which has much of a thematic and symbolic nature in common with its forerunners, Equus and The Royal Hunt of the Sun, stemming genetically from the unique sibling rivalry of twinship, there is more pronounced emphasis on the influence of envy and vengeance on human behavior than in the other two plays. It is postulated that the success of Equus and its implications pertinent to the competitive aspect of the relationship with his twin brother stirred appreciable intrapsychic turmoil in Shaffer and was a decisive motivating factor in his writing of Amadeus.

Humans↗
PubMed1995

The accuracy of acoustic rhinometry using a pulse train signal.

The signal used in the original acoustic rhinometers was an impulse of short duration and wide energy spectrum. A rhinometer utilizing a new signal of a similarly broad energy but different time course has been developed. We investigated the accuracy of area reconstructions computed using this signal by comparing them with the original areas of simple models. This study demonstrates that, at present, acoustic rhinometry using a pulse train signal is subject to significant systematic errors. Some of these are intrinsic to the rhinometer. Others are caused by the geometry of the models. Areas reconstructions beyond narrow constrictions are particularly inaccurate. The findings are significant because the nasal valve can act as such a constriction. The errors can cause the parameters used in the clinical application of acoustic rhinometry to deviate substantially from the true values.

Acoustic Stimulation↗
PubMed1995

To see the Thing Itself: the influence of early object loss on the life and art of Edward Weston.

Using journals, letters, dreams, early memories, and anniversary phenomena as a clinical data base, an attempt has been made to demonstrate how Edward Weston sought to master the psychic trauma imposed at age 5 by the death of his mother through the medium of photography. His photographic artistry came to dominate his entire life, with nature acting as a symbolic maternal substitute and supplying him with a wealth of material for his work. The circumscribed image of his mother's eyes during her last days, the only recollection he had of her, was a crucial element in his becoming a photographer, whose camera was his one constant love attachment.

Art↗
PubMed1995

Limitations of acoustic rhinometry determined by a simple model.

To determine the accuracy of a commercially available transient signal acoustic rhinometer we constructed simple models from tubing of known dimensions. A series of models was constructed in which the main cylinder was constant whilst the aperture of an included constricted area was varied from 0.07 cm2-0.95 cm2. The area reconstruction for each model was then compared with the true area. Two parameters based on those used in clinical practice of acoustic rhinometry were employed to evaluate the error. The results demonstrate that the measurement of both the volume beyond a constriction and the area of the constriction may be associated with systematic errors. The reconstructed profile of each model is similarly erroneous. As the nose presents a proximal constriction, these findings are of considerable relevance to the clinical use of acoustic rhinometry.

Acoustics↗
PubMed1994

Development regulation of basal and hormone-inducible phosphoenolpyruvate carboxykinase gene expression in chick embryo liver in vivo.

We have examined cytosolic phosphoenolpyruvate carboxykinase (PEPCK, EC 4.1.1.32) gene transcription and steady-state mRNA expression in chick embryo liver in vivo both constitutively and in response to dexamethasone, cAMP, retinoic acid, and the protein synthesis inhibitors, cycloheximide and pactamycin. We report here that PEPCK mRNA is constitutively expressed between 12 and 16 days of development. PEPCK expression was also transiently but highly inducible on Day 14 by dexamethasone, cAMP, cycloheximide, and pactamycin, but not by retinoic acid. Cycloheximide pretreatment had an additive or synergistic effect on the induction by dexamethasone and/or cAMP. Dexamethasone- and cycloheximide-induced increases in mRNA expression were principally due to increases in the rate of PEPCK gene transcription. Following an initial induction by dexamethasone, PEPCK expression was no longer responsive to a second administration of dexamethasone but was still responsive to cycloheximide and cAMP. PEPCK induction by dexamethasone or cycloheximide progressively diminished between 12 and 15 days of development. By Day 16, PEPCK expression was no longer responsive to dexamethasone, but was still inducible by cAMP and this induction was increased by cycloheximide. These results indicate that PEPCK is transiently inducible by glucocorticoids in chick embryo liver and that there are two developmental switches to the adult phenotype between Days 14 and 16 of development and between Day 16 and 4 days posthatching. Our results also suggest the presence of a developmentally regulated repressor of PEPCK gene expression in chick embryo liver.

Animals↗
PubMed1994

Comparison of effects of direct-acting DNA methylating and ethylating agents on inducible gene expression in vivo.

Our laboratory is interested in whether chemical carcinogen-induced DNA damage is non-randomly distributed in the genome, i.e., "targeted," at the level of individual genes. As one means of investigating this, we have examined whether carcinogen treatment differentially alters the expression of specific genes in vivo. In this study, we have compared the effects of four direct-acting simple alkylating agents (methyl methanesulfonate, ethyl methanesulfonate, methylnitrosourea, and ethylnitrosourea) on the steady-state mRNA expression of a model inducible gene, phosphoenolpyruvate carboxykinase (PEPCK), using the chick embryo as a simple in vivo test system. We observed no effect of any of these four carcinogens on the steady-state mRNA expression of the constitutively expressed beta-actin, transferrin, or albumin genes in chick embryo liver following a single dose of carcinogen. In contrast, these same treatments significantly altered both the basal and inducible expression of the glucocorticoid-inducible PEPCK gene. These results support the hypothesis that inducible gene expression is a target for the effects of chemical carcinogens in vivo. In addition, the direction, magnitude, and time course of these effects were agent-specific. Qualitative and quantitative differences in effects between the methylating and ethylating agents and between the methanesulfonates and nitrosoureas were correlated with differences in their specific patterns of DNA adduct formation, suggesting that different DNA lesions have different effects on inducible gene expression.

Alkylating Agents↗
PubMed1994

Effects of the genotoxic carcinogen chromium(VI) on basal and hormone-inducible phosphoenolpyruvate carboxykinase gene expression in vivo: correlation with glucocorticoid- and developmentally regulated expression.

Previous studies have shown that a number of different genotoxic carcinogens that induce different types of DNA damage preferentially alter the expression of inducible genes in vivo. To investigate further the mechanistic basis for these effects, we examined the effects of the human lung carcinogen chromium(VI) on expression of the hormone-inducible cytosolic phosphoenolpyruvate carboxykinase (PEPCK) gene in chick embryo liver. Chromium(VI) pretreatment had significant effects on both basal and glucocorticoid-inducible PEPCK expression in 14-d-old embryo liver. These effects were principally a result of changes in PEPCK transcription. In contrast, treatment with chromium(VI) 1 h after treatment with glucocorticoid had no effect on PEPCK induction, suggesting that an early event in the induction process is the target for carcinogen effects. In 16-d-old liver, in which PEPCK expression is no longer responsive to glucocorticoid induction, both basal and inducible PEPCK expression were also refractory to chromium(VI) effects, indicating that carcinogen responsiveness is a phenotypic rather than an inherent property of inducible genes and is related to their competence for induction. Chromium(VI) had no effect on cAMP induction of PEPCK expression, demonstrating that carcinogens target their effects to specific regulatory pathways. Comparison of the effects of chromium(VI) with those of cycloheximide suggests that chromium(VI) targets its effects to a labile, constitutively expressed repressor involved in PEPCK gene regulation.

Animals↗
PubMed1994

The genotoxic carcinogen chromium(VI) alters the metal-inducible expression but not the basal expression of the metallothionein gene in vivo.

The ability of the carcinogen chromium(VI) to affect the basal and zinc-inducible expression of liver metallothionein was examined in 14- and 18-day chicken embryos in vivo. Metallothionein expression varied with the stage of embryo development, with basal steady-state mRNA levels being approximately three times lower in livers of 18-day versus 14-day chicken embryos. Chromium(VI) treatment had no effect on the basal steady-state levels of metallothionein mRNA and protein in either 14- or 18-day chicken embryo liver. Treatment of 14-day embryos with zinc(II) resulted in a 3- to 5-fold increase in steady-state levels of metallothionein mRNA in liver. Pre-treatment of 14-day embryos with chromium(VI) inhibited the zinc(II)-induced increase in steady-state levels of metallothionein mRNA and protein in liver by 30-50%. In contrast, chromium(VI) and/or zinc(II) treatments had no effect on steady-state levels of beta-actin mRNA.

Animals↗
PubMed1994

Processing of chromogranin A by bovine parathyroid secretory granules: production and secretion of N-terminal fragments.

Chromogranin A (CgA) is a glycoprotein located in the secretory granules of multiple neuroendocrine tissues, including the parathyroid gland. Although the function of CgA is not known, a role has been proposed for CgA as a prohormone for biologically active peptides. Using 3H-CgA as a substrate for bovine parathyroid secretory granule extracts, we demonstrate a precursor product relationship between intact CgA and multiple N-terminal fragments of CgA. N-terminal CgA fragments of mol wt 24, 26, and 33 k are generated in a time dependent manner in the presence of bovine parathyroid secretory granule enzymes. The generation of the 33 kilodalton (kDa) N-terminal CgA fragment is calcium dependent. In the presence of EDTA, intermediate CgA fragments of mol wt 36 and 45 are generated. The effect of EDTA is reversible with added calcium. Based on immunodetection on Western blots, the 26 kDa N-terminal fragment of CgA is secreted by bovine parathyroid cells in a time and calcium-dependent manner in parallel with PTH and intact CgA. The secretion of the 26 kDa N-terminal fragment of CgA increases in response to low calcium incubation conditions and is suppressed by high calcium incubation conditions. We conclude that bovine parathyroid secretory granules contain enzymatic activity capable of processing CgA to multiple N-terminal fragments. The secretion of at least one N-terminal fragment (26 kDa) is calcium responsive. The physiological significance of CgA processing in parathyroid secretory granules is as yet unknown.

Amino Acids↗
PubMed1993

Preferential alteration of inducible gene expression in vivo by carcinogens that induce bulky DNA lesions.

Our laboratory is interested in whether chemical carcinogen-induced DNA damage is nonrandomly distributed in the genome, i.e., "targeted," at the level of individual genes. To examine this, we have been investigating whether carcinogen treatment in vivo differentially alters the expression of specific genes. In this study, we examined the effects of four model carcinogens that induce bulky lesions in DNA--benzo[a]pyrene (B[a]P), aflatoxin B1 (AFB1), 7,12-dimethylbenz[a]anthracene (DMBA), and 2-acetylaminofluorene (AAF)--on the steady-state mRNA expression of several constitutive and drug-inducible genes in vivo. We specifically tested the hypothesis that carcinogen-induced DNA damage is preferentially targeted to inducible genes relative to constitutively expressed genes using the chick embryo as a simple in vivo test system. In summary, the four carcinogens had no effect on the steady-state mRNA expression of constitutively expressed beta-actin, transferrin, or albumin genes over a 24-h period after a single dose of each carcinogen. In contrast, each of these same treatments significantly altered the mRNA expression of two glutethimide-inducible genes, ALA synthase and CYP2H1. Both the basal expression of these genes and their drug-inducible expression was altered. B[a]P and AFB1 had similar effects on expression of the two inducible genes and caused similar levels of covalent adducts in total DNA, even though the administered doses differed by 30-fold. B[a]P binding to DNA, and the basal expression of CYP2H1 were similar in liver and lung. However, B[a]P significantly altered basal CYP2H1 mRNA expression in liver, a tissue in which this gene is highly inducible by glutethimide, and had no effect on basal CYP2H1 mRNA expression in lung, a tissue in which this gene is not drug-inducible. These data support the hypothesis that inducible gene expression is a target for carcinogen-induced DNA damage in vivo.

5-Aminolevulinate Synthetase↗
PubMed1993

On typographical errors.

In his overall assessment of parapraxes in 1901, Freud included typographical mistakes but did not elaborate on or study this subject nor did he have anything to say about it in his later writings. This paper lists textual errors from a variety of current literary sources and explores the dynamic importance of their execution and the failure to make necessary corrections during the editorial process. While there has been a deemphasis of the role of unconscious determinants in the genesis of all slips as a result of recent findings in cognitive psychology, the examples offered suggest that, with respect to motivation, lapses in compulsivity contribute to their original commission while thematic compliance and voyeuristic issues are important in their not being discovered prior to publication.

Female↗
PubMed1992

Regulated, but not constitutive, secretory proteins bind porcine chymotrypsinogen.

Endocrine and exocrine cells exhibit both a constitutive and a regulated secretory pathway. In the latter pathway, secretory proteins are stored at a high concentration in secretory granules and are released by exocytosis in response to appropriate external stimuli. Sorting between the two secretory pathways is believed to take place in the trans-Golgi tubular network. To account for experimental data, it has been proposed that sorting receptors exist which bind a variety of regulated secretory proteins, including foreign secretory proteins introduced into the cells by transfection. In support of the sorting receptor hypothesis Chung et al. (Chung, K.-N., Walter, P., Aponte, G. W., and Moore, H.-P.H. (1989) Science 243, 192-197) isolated a group of 25-kDa canine pancreatic "hormone-binding proteins" that bound regulated but not constitutive secretory proteins. To determine if similar proteins are present in other species and tissues, we have screened porcine pancreas, parathyroid, adrenal medulla, and pituitary glands. A 31-kDa protein, similar to that identified by Chung et al. (1989), which binds to regulated but not to constitutive secretory proteins was identified in porcine pancreas. This protein was not detected in the parathyroid, adrenal medulla, or pituitary glands, however, which argues against it serving as a general sorting receptor. NH2-terminal sequencing, immunoreactivity, and proteolytic activity data indicate that the porcine 31-kDa protein is similar if not identical to porcine chymotrypsinogen A or B.

Adrenal Medulla↗
PubMed1992

Inhibition of protein synthesis increases the transcription of the phenobarbital-inducible CYP2H1 and CYP2H2 genes in chick embryo hepatocytes.

The mechanism by which phenobarbital and similar compounds regulate gene expression has remained elusive for many years despite intense investigation. We had previously reported that the mRNA expression for the phenobarbital-inducible CYP2H1 gene was increased by cycloheximide treatment as rapidly and to a similar extent as by the phenobarbital-type drugs glutethimide and 2-propyl-2-isopropylacetamide (PIA), in primary cultures of chick embryo hepatocytes or in chick embryo liver in vivo (J. W. Hamilton, W. J. Bement, P. R. Sinclair, J. F. Sinclair, and K. E. Wetterhahn, 1988, Biochem. J. 255, 267-275). To examine the mechanism of this induction further, we determined the effects of various structurally related and unrelated inhibitors of protein synthesis on CYP2H1 expression in cultured chick embryo hepatocytes. Cycloheximide increased the transcription rate of the CYP2H1/2 genes to a similar extent as did PIA, and had little or no effect on CYP2H1 mRNA half-life. A number of other protein synthesis inhibitors, including streptovitacin, acetoxycycloheximide, pactamycin, and ricin, all increased CYP2H1 mRNA expression to a similar extent. The dose responses for induction of CYP2H1 mRNA and inhibition of protein synthesis by these agents were closely correlated. There was no relationship between the effectiveness of these agents to induce CYP2H1 mRNA expression and their structures or lipophilicity. Cycloheximide acetate required deesterification to cycloheximide for both inhibition of protein synthesis and induction of CYP2H1 mRNA. These results suggest that a labile negative regulatory protein is involved in CYP2H1/2 gene expression. It is also possible that this factor is involved in regulating the phenobarbital response of CYP2H1/2.

Animals↗