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Biomedical subjects

J Henry

Publications and source records attributed to J Henry.

At least 19 recordsLinked to original sources
PubMed1999

Modulation of gastrin processing by vesicular monoamine transporter type 1 (VMAT1) in rat gastrin cells.

1. Gastrointestinal endocrine cells produce biogenic amines which are transported into secretory vesicles by one of two proton-amine exchangers, vesicular monoamine transporters type 1 and 2 (VMAT1 and 2). We report here the presence of VMAT1 in rat gastrin (G) cells and the relevance of VMAT1 function for the modulation of progastrin processing by biogenic and dietary amines. 2. In immunocytochemical studies VMAT1, but not VMAT2, was localized to subpopulations of G cells and enterochromaffin (EC) cells; neither was found in antral D cells. The expression of VMAT1 in antral mucosa was confirmed by Northern blot analysis, which revealed an mRNA band of approximately 3.2 kb, and by Western blot analysis, which revealed a major protein of 55 kDa. 3. In pulse-chase labelling experiments, the conversion of the amidated gastrin G34 to G17 was inhibited by biogenic amine precursors (L-DOPA and 5-hydroxytryptophan). This inhibition was stereospecific and sensitive to reserpine (50 nM), which blocks VMAT1 and VMAT2, but resistant to tetrabenazine, which is a selective inhibitor of VMAT2. 4. Dietary amines such as tyramine and tryptamine also inhibited G34 cleavage. This effect was associated with a loss of the electron-dense core of G cell secretory vesicles. It was not stereospecific or reserpine sensitive, but was correlated with hydrophobicity. 5. Thus rat antral G cells can express VMAT1; transport of biogenic amines into secretory vesicles by VMAT1 is associated with inhibition of G34 cleavage, perhaps by raising intravesicular pH. Dietary amines also modulate cleavage of progastrin-derived peptides, but do so by a VMAT1-independent mechanism; they may act as weak bases that passively permeate secretory vesicle membranes and raise intravesicular pH.

Amino Acids↗
PubMed1999

A comparison of fatal with non-fatal knife injuries in Edinburgh.

Assault using a knife is a common problem in the United Kingdom. Between February 1992 and December 1996, 120 individuals died or received hospital treatment in Edinburgh after being assaulted with a knife. Twenty individuals (17%) died as a result of their injuries. Comparison of the survivors with non-survivors revealed both groups to have similar age and sex distributions, but those who died had significantly more severe injuries when scored according to the Abbreviated Injury Scale. Eight individuals died of unsurvivable chest injuries at the scene of the attack and of the remainder, only five reached hospital with signs of life. Analysis of hospital treatment using TRISS methodology revealed there to be two unexpected survivors and no unexpected deaths. The risk of death appears to depend mostly upon injuries sustained and also to a lesser extent upon other factors such as alcohol consumption and the presence of a bystander capable and willing to request emergency medical assistance. There does not appear to be much potential to save lives by improving hospital treatment for those assaulted with a knife in Edinburgh. Instead, greater focus needs to be placed upon rapid transfer to hospital and upon restricting the possession and use of knives.

Adolescent↗
PubMed1999

The association between seniority of Accident and Emergency doctor and outcome following trauma.

The actual survival of patients treated following trauma in four Scottish Teaching hospitals during five years was compared with predicted survival according to TRISS analysis. The data were analysed according to the seniority of the Accident and Emergency (A&E) doctor treating each patient. The group of patients treated by a consultant had a significantly better outcome (p < 0.05) than the group of patients treated by junior doctors. Analysis of outcome according to the grade of junior A&E doctor suggested a step-wise improvement in outcome with seniority, thus supporting the concept that an improved outcome is associated with experience and seniority. These results support calls for A&E consultants to be increasingly involved in the management of patients with major trauma. Such increased involvement would require an increase in the number of A&E consultants.

Chi-Square Distribution↗
PubMed1999

Structure and evolution of the extended B7 family.

Here, Joëlle Henry and colleagues explore structural and evolutionary relationships between the B7 costimulator molecules and a growing number of molecules encoded within the major histocompatibility complex. They propose that B7 and MHC genes are derived from a common ancestor, with several members of this large gene family possibly having pivotal influences on T-cell activation.

Amino Acid Sequence↗
PubMed1999

Peptidergic control of egg-laying in the cephalopod Sepia officinalis: involvement of FMRFamide and FMRFamide-related peptides.

The peptidergic control of egg-laying was investigated in Sepia officinalis by using a myotropic bioassay. Three myotropic high-performance liquid chromatography fractions were obtained from optic lobe extracts. In the first fraction, FMRFamide (FMRFa) and FLRFa were isolated and sequenced. FMRFa-related peptides then were sought by dotting immunobinding of optic lobes extracts. The four immunoreactive fractions detected revealed the occurrence of FMRFa, FLRFa, FIRFa, and ALSGDAFLRFa predicted by the precursor already cloned from the optic lobes of S. officinalis (J Exp Biol 200:1483-9;1997). These peptides clearly appeared to be involved in the regulation of oocyte transport through the oviduct: the tetrapeptides FMRFa and FLRFa stimulated the contractions, whereas FIRFa and ALSGDAFLRFa lowered the tonus, the frequency, and the amplitude of the contractions. The occurrence of FaRPs in the nervous endings of the accessory sex glands suggested that this peptide family is involved in the regulation of secretory processes of the egg capsule. Indeed, FMRFa modulates the contractions of the main nidamental glands in vitro and, thus, should induce mechanical release of the secretion in vivo during ovulation. These results show that the FaRPs could play an important role in the synchronization of ovulation and egg capsule coating.

Animals↗
PubMed1999

[Pulmonary lymphangioleiomyomatosis: an often fortuitous diagnosis. A case report].

INTRODUCTION: Lymphangioleiomyomatosis is an uncommon disorder of unknown origin, which exclusively occurs in women of reproductive age. The condition is characterized by proliferation of immature smooth muscle cells throughout the lungs, i.e., in the peribronchial, perilymphatic, and perivascular areas. This results in obliteration of the respiratory tract and in the development of cysts. Lymphangioleiomyomatosis has a poor prognosis due to both numerous lung complications and progression of the disease to respiratory failure. EXEGESIS: We report the case of a patient in whom lymphangioleiomyomatosis was fortuitously diagnosed from chest CT scan, itself performed for the diagnosis of pulmonary embolism. This case is therefore of particular interest. CONCLUSION: Our results suggest that the prevalence of lymphangioleiomyomatosis is probably underestimated due to its clinical latency and the absence of specific laboratory tests. Therefore, the development of non-invasive radiological methods should permit early diagnosis of the disease.

Adult↗
PubMed1999

An inpatient treatment model for adults with mild intellectual disability and challenging behaviour.

Following the closure of the large mental handicap hospitals in the UK, the majority of people with intellectual disability (ID) are currently living in the community. However, people with ID who also exhibit challenging behaviour (CB) have been the most difficult-to-place group and use a large amount of service resources. A variety of service options have been proposed for the assessment and treatment of CBs, but there is little information on the effectiveness of these alternatives. The Mental Impairment Evaluation and Treatment Service (MIETS) is one of these service options and the aim of the present study is to describe and evaluate this service. The present authors studied the first 64 patients admitted to MIETS following its opening. A within-subject comparison research design was used. Demographic and clinical data were obtained from case records and the effectiveness of MIETS interventions was evaluated by comparing the number of incidents of challenging behaviour, the use of seclusion, and the place of residence before and after the MIETS intervention. Only 10 (17.5%) of the patients had been admitted from community facilities, but 48 (84.2%) of the patients were discharged to community placements (P < 0.000 I1). The MIETS also significantly reduced the frequency and severity of challenging behaviours (P < 0.0001). It is concluded that the MIETS is an effective treatment model for people with ID and CB, and that there is no place for therapeutic nihilism in this difficult-to-place group of patients.

Adolescent↗
PubMed1999

Substrate oxidation by the portal drained viscera of fed piglets.

Fully fed piglets (28 days old, 7-8 kg) bearing portal, arterial, and gastric catheters and a portal flow probe were infused with enteral [U-(13)C]glutamate (n = 4), enteral [U-(13)C]glucose (n = 4), intravenous [U-(13)C]glucose (n = 4), or intravenous [U-(13)C]glutamine (n = 3). A total of 94% of the enteral [U-(13)C]glutamate but only 6% of the enteral [U- (13)C]glucose was utilized in first pass by the portal-drained viscera (PDV). The PDV extracted 6.5% of the arterial flux of [U-(13)C]glucose and 20.4% of the arterial flux of [U-(13)C]glutamine. The production of (13)CO(2) (percentage of dose) by the PDV from enteral glucose (3%), arterial glucose (27%), enteral glutamate (52%), and arterial glutamine (70%) varied widely. The substrates contributed 15% (enteral glucose), 19% (arterial glutamine), 29% (arterial glucose), and 36% (enteral glutamate) of the total production of CO(2) by the PDV. Enteral glucose accounted for 18% of the portal alanine and 31% of the portal lactate carbon outflow. We conclude that, in vivo, three-fourths of the energy needs of the PDV are satisfied by the oxidation of glucose, glutamate, and glutamine, and that dietary glutamate is the most important single contributor to mucosal oxidative energy generation.

Alanine↗
PubMed1999

The cytotoxicity and mode of action of 2,3,4-trisubstituted pyrroles and related derivatives in human Tmolt4 leukemia cells.

4-Carbethoxy-1-methyl-2-phenacyl-3-phenylpyrrole (9), 4-carbethoxy-2-(4-methoxybenzoyl)-3-(4-methoxyphenyl)pyrrole (10) and 2-(4-methoxybenzoyl)-3,4-bis-(4-methoxyphenyl)pyrrole (11) proved to be potent cytotoxic agents against the growth of murine and human leukemias and lymphomas. Selective toxicity was demonstrated against the growth of solid tumors, e.g., human adenocarcinoma of the colon SW480 and ileum HCT-8, glioma U-87-MG, and rat UMR-106 osteosarcoma. A mode of action study in Tmolt4 leukemia cells demonstrated that the agents inhibited de novo purine synthesis at the regulatory sites PRPP-amido transferase, IMP dehydrogenase as well as dihydrofolate reductase resulting in significant inhibition of DNA synthesis in 60 min. Other biochemical sites which were affected significantly were thymidylate synthetase, DNA polymerase alpha, RNA polymerases, nucleoside kinase and ribonucleoside reductase.

Animals↗
PubMed1998

Increased survival after serious injury in patients admitted directly to critical care areas from the accident and emergency department.

OBJECTIVES: We hypothesised that, in the subgroup of seriously injured patients who receive early critical care in the operating theatre or intensive care unit, there would be a greater actual survival rate than that statistically predicted using trauma scoring techniques. METHODS: 1031 seriously injured patients on a national trauma database were analysed. The numbers of survivors in 3 initial destination groups [intensive care unit (ICU), theatre and ward] were compared with the average number of survivors statistically predicted for similar groups of patients using the TRISS methodology. W statistics were then used to test for statistical significance. RESULTS: 77/122 patients admitted to an ICU survived (predicted number 66, W stat 8.8 [2.6-15.0]). 129/178 patients transferred to theatre survived (predicted number 113, W stat 8.8 [4.2-13.5]). 296/348 patients admitted to a ward survived (predicted number 292, W stat 1.3 [-1.9-4.4]). CONCLUSIONS: The number of patients who survive after severe injury is significantly greater than the number predicted to survive by current trauma scoring methods if the patient is sent directly to theatre or are admitted directly to the ICU. Survival is as predicted if the patient is sent initially to a ward.

Adolescent↗
PubMed1998

Catabolism dominates the first-pass intestinal metabolism of dietary essential amino acids in milk protein-fed piglets.

To investigate the extent of first-pass intestinal metabolism of dietary amino acids, seven female pigs (28 d old, 8.0 kg) were implanted with arterial, venous, portal and gastric catheters and with an ultrasonic portal blood flow probe. The pigs were fed a milk-based diet once hourly and infused intragastrically with [U-13C]algal protein. On average, 56% of the essential amino acid (EAA) intake appeared in the portal blood. However, the net portal balance of methionine (48% of intake) and threonine (38% of intake) tended (P = 0.08) to be lower than the mean of all EAA. The net portal balance (expressed as a percentage of intake) of alanine (205%), tyrosine (167%) and arginine (137%) exceeded their intake. Net portal outflow of ammonia accounted for 18% of total amino acid nitrogen intake. As a percentage of the enteral tracer input, there was substantial first-pass metabolism of lysine (35%), leucine (32%), phenylalanine (35%) and threonine (61%). However, only 18, 21, 18 and 12% of the total first-pass metabolism of lysine, leucine, phenylalanine and threonine, respectively, were recovered in mucosal protein. We conclude that roughly one third of dietary intake of EAA is consumed in first-pass metabolism by the intestine and that amino acid catabolism by the mucosal cells is quantitatively greater than amino acid incorporation into mucosal protein.

Amino Acids↗
PubMed1998

Dietary amino acids are the preferential source of hepatic protein synthesis in piglets.

To investigate the utilization of dietary amino acids for hepatic protein synthesis, seven female pigs ( 28 d old, 7.5 kg) were implanted with catheters in a carotid artery, the jugular and portal veins, and the stomach. A portal flow probe was also implanted. The pigs were fed a high protein diet once hourly and infused intragastrically with [U-13C]algal protein for 6 h. Amino acid labeling was measured in arterial and portal blood, in the hepatic free and protein-bound pools and in apolipoprotein B-100 (apoB-100), albumin and fibrinogen. The isotopic enrichments of apoB-100-bound [U-13C]threonine, leucine, lysine and phenylalanine were 33, 100, 194 and 230% higher than those of their respective hepatic free amino acid pools (P < 0.01). Using the labeling of apoB-100 to estimate that of the protein synthetic precursor, the fractional rate of hepatic protein synthesis was 42 +/- 2%/d. Between 5 and 8% of the dietary tracer amino acids was used for hepatic protein synthesis. In contrast to the small intestinal mucosa, in which the majority of the metabolized amino acids were apparently catabolized, protein synthesis utilized from 48% (threonine) to 90% (lysine) of the hepatic uptake of tracer amino acids. It appears that hepatic protein synthesis consumes nutritionally significant quantities of dietary essential amino acids in first pass and that extracellular, especially portal, essential amino acids are channeled to hepatic protein synthesis in the fed state.

Albumins↗
PubMed1998

B30.2-like domain proteins: update and new insights into a rapidly expanding family of proteins.

The B30.2 domain is a conserved region of around 170 amino acids associated with several different protein domains, including the immunoglobulin folds of butyrophilin and the RING finger domain of ret finger protein. We recently reported several novel members of this family as well as previously undescribed protein families possessing the B30.2 domain. Many proteins have subsequently been found to possess this domain, including pyrin/marenostrin and the midline 1 (MID1) protein. Mutations in the B30.2 domain of pyrin/marenostrin are implicated in familial Mediterranean fever, and partial loss of the B30.2 domain of MID1 is responsible for Opitz G/BBB syndrome, characterized by developmental midline defects. In this study, we scrutinized the available sequence data bases for the identification of novel B30.2 domain proteins using highly sensitive database-searching tools. In addition, we discuss the chromosomal localization of genes in the B30.2 family, since the encoded proteins are likely to be involved in other forms of periodic fever, autoimmune, and genetic diseases.

Amino Acid Sequence↗
PubMed1998

Acute pancreatitis induces cytokine production in endotoxin-resistant mice.

OBJECTIVE: The purpose of this study was to determine whether pathologic progression and cytokine responses in acute pancreatitis (AP) are altered in the absence of endotoxemia. SUMMARY BACKGROUND DATA: Previous studies have demonstrated that AP is characterized by rapid production and release of inflammatory cytokines, which play a major role in the local pancreatic and systemic complications of this disease. Infection and endotoxemia have been implicated as a major source of morbidity and death in AP and as possible stimuli for the overwhelming cytokine response seen in this disease. METHODS: AP was induced by a choline-deficient and ethionine-supplemented diet for 4 days in normal C57BL/6J mice (controls, n = 23) and in CD14 knockout mice (CD14KO, n = 23), which cannot produce circulating cytokines in response to endotoxin. Control and endotoxin-resistant mice were killed at time 0, then at 24, 48, 72, and 96 hours after the start of the diet. At each time point serum was collected for amylase, glucose, and cytokine measurements (tumor necrosis factor-alpha [TNFalpha] and interleukin-1beta [IL1beta]), and the pancreas was removed for histologic examination. TNFalpha was measured with a bioassay using WEHI-2F cells and IL1beta with a bioassay using D10.G4.1 cells. RESULTS: CD14KO mice developed biochemical manifestations of AP with alterations in amylase levels, hypoglycemia, weight loss, and histologic changes of pancreatitis similar to the pattern seen in control mice. TNFalpha and IL1beta production had similar kinetics in both groups, with significant peak TNFalpha serum levels at 72 hours and a progressive rise of IL1beta levels throughout the study period. Histologic changes appeared earlier and were more pronounced in the control versus the CD14KO mice. However, the mortality rate was identical (20% at 96 hours) for both groups. CONCLUSIONS: These results demonstrate that the progression of AP, the cytokine response associated with the disease, and early death are independent of endotoxin action. These findings, which suggest that an uncharacterized stimulus is responsible for triggering the cytokine cascade in this disease, may have significant implications for the management of patients with AP.

Acute Disease↗
PubMed1998

Collaboration between schools of nursing and local education agencies to provide health care services to pre-kindergarten through twelfth grade students: elements of cooperative agreements.

Establishing cooperative relationships between schools of nursing and local education agencies for the delivery of health care services to children from pre-school through the twelfth grade is a process all too often characterized by numerous legal, insurance, and administrative roadblocks. While nursing faculty and their students may wish to cooperate with professional educators and their students to enhance the health care of the children, there are obstacles. Both institutions are represented by attorneys, insurance companies and others who must attend to aspects of the process other than direct health care delivery. A model for joint planning and a list of elements of effective agreements are offered as a way of engaging all parties in a constructive and useful process of collaboration.

Adolescent↗
PubMed1997

B30.2-like domain proteins: a growing family.

The B30.2 domain is a conserved domain of around 170 amino acids. It is found associated with different protein domains: immunoglobulin domain in the case of butyrophilin and Ring Finger domain in the case of Ret Finger Protein. B30.2 should therefore be considered a migratory domain. We here report new members of these families as well as new protein families having the B30.2 domain, and we tentatively propose a general function for this domain.

Amino Acid Sequence↗
PubMed1997

Amine precursor uptake and decarboxylation: significance for processing of the rat gastrin precursor.

1. Conversion of prohormone precursors to smaller active products occurs in secretory granules, which also have the capacity to concentrate biogenic amines. We have examined how processing of the gastrin precursor, progastrin, in rat antral mucosa is influenced by modulation of the biogenic amine content of secretory granules. 2. Newly synthesized progastrin-derived peptides in rat antral mucosa were labelled in vitro with 35SO4(2-) using a pulse-chase protocol and detected after immunoprecipitation by HPLC with on-line liquid scintillation counting. Secretory granule morphology was examined by electron microscopy. The effects of experimentally manipulating secretory granule pH and amine content were examined. 3. The dopamine precursor L-beta-3,4-dihydroxyphenylalanine (L-DOPA) inhibited cleavage of 35S-labelled thirty-four amino acid amidated gastrin, i.e. [35S]G34, and of [35S]G34 with COOH-terminal glycine, i.e. [35S]G34-Gly, at a pair of lysine residues, but did not influence cleavage of progastrin at pairs of arginine residues. The effect of L-DOPA was reversed by reserpine, which inhibits the amine-proton exchangers VMAT1 and VMAT2, and by carbidopa, which inhibits aromatic L-amino acid decarboxylase. 4. Treatments that raise intragranular pH, e.g. the weak base chloroquine, the ionophore monensin and the vacuolar proton pump inhibitor bafilomycin A1, had similar effects to L-DOPA. 5. Electron microscopical studies showed that the electron-dense aggregrates in gastrin cell secretory granules were lost after inhibition of the vacuolar proton pump. Treatment with L-DOPA produced reserpine-sensitive dissipation of the electron-dense aggregates, compatible with the idea that increased amine delivery raised intragranular pH. 6. The data suggest that the processes of amine precursor uptake, decarboxylation and sequestration in secretory granules are associated with selective modulation of progastrin cleavage, possibly by raising intragranular pH and thereby inhibiting pH-sensitive prohormone convertases.

Adrenergic Uptake Inhibitors↗