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Biomedical subjects

J Henry

Publications and source records attributed to J Henry.

At least 19 recordsLinked to original sources

Evidence of 5-hydroxytryptamine synthesis in the follicles of Sepia officinalis and direct involvement in the control of egg-laying.

At the beginning of egg-laying, in the cuttlefish Sepia officinalis, the oocytes accumulated in the proximal oviduct are released into the mantle cavity by the contractions of the oviduct before being encapsulated and fertilised. A bioassay based on the recording of the contractile activity of the distal oviduct was performed to characterise the molecule(s) inhibiting the oviducal motility and then responsible for the storage of the oocytes before mating. From 200 full-grown oocytes, a factor lowering the oviducal contractions was purified and isolated by means of HPLC. ESI-MS as well as electrochemical detection following HPLC fractionation allowed identification of the 5-hydroxytryptamine in the pure fraction. The inhibition of the oviducal contractions by 5-HT was dose dependent with a threshold near 10(-7) M. An immunoenzymatic assay showed that 5-HT appeared in the follicles at the beginning of vitellogenesis and reached a maximum level in the full-grown oocytes. In vitro experiments revealed that 5-HT is synthesised by the follicular cells and the full-grown oocytes, before being released to target proximal oviduct. Thus 5-HT could be one of the molecules involved in the accumulation of oocytes in the oviduct before mating. Mol. Reprod. Dev. 55:182-188, 2000.

Animals

Application of neural networks and sensitivity analysis to improved prediction of trauma survival.

The performance of trauma departments is widely audited by applying predictive models that assess probability of survival, and examining the rate of unexpected survivals and deaths. Although the TRISS methodology, a logistic regression modelling technique, is still the de facto standard, it is known that neural network models perform better. A key issue when applying neural network models is the selection of input variables. This paper proposes a novel form of sensitivity analysis, which is simpler to apply than existing techniques, and can be used for both numeric and nominal input variables. The technique is applied to the audit survival problem, and used to analyse the TRISS variables. The conclusions discuss the implications for the design of further improved scoring schemes and predictive models.

Analysis of Variance

Quantitative measurement of P- and E-selectin adhesion molecules in acute pancreatitis: correlation with distant organ injury.

OBJECTIVE: To determine whether expression of P- and E-selectin molecules is associated with the development of systemic organ manifestations in acute pancreatitis (AP). SUMMARY BACKGROUND DATA: Overproduction of inflammatory cytokines in AP induces expression of adhesion molecules, which may lead to increased leukocytic infiltration and tissue damage. Understanding the temporal expression of these molecules could afford better measures for therapeutic intervention. METHODS: Acute pancreatitis was induced in 30-day-old female C57/ bI/6J mice by feeding a choline-deficient/ethionine-supplemented diet (n = 95). Mice were divided into three groups. Group I (n = 35) was used to study the biochemical and histologic manifestations of AP and to evaluate the neutrophilic infiltration by myeloperoxidase activity and immunofluorescence. Groups II (n = 35) and III (n = 25) were used to evaluate expression of P- and E-selectin by the dual radiolabeled monoclonal antibody technique. RESULTS: Biochemical and histologic evidence of AP developed in all mice. The inflammatory cytokine tumor necrosis factor-alpha gradually increased in serum as early as 18 hours, reaching more than 800-fold background levels by 72 hours. Biphasic P-selectin expression in the lung was seen with peaks at 24 and 48 hours; E-selectin expression peaked at 48 hours. CD18-positive leukocytes and increased myeloperoxidase activity in the lung were demonstrated at 24 hours, correlating with the onset of selectin upregulation. Histologic scoring of lung tissue demonstrated mild damage at 24 hours, with progressive injury occurring from 48 to 72 hours. CONCLUSIONS: In AP, the production of inflammatory cytokines precedes up-regulation of P- and E-selectin, whose expression coincided with the increased infiltration of CD18-positive cells and neutrophil sequestration in lung tissue. Temporally, these events correlate with evidence of histologic pulmonary injury and underscore the role of adhesion molecules as mediators of pathophysiologic events. This mechanistic pathway may afford novel therapeutic interventions in clinical disease by using blocking agents to ameliorate the systemic manifestations of AP.

Acute Disease

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

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

Unsedated small-caliber esophagogastroduodenoscopy (EGD) versus conventional EGD: a comparative study.

BACKGROUND & AIMS: Significant portions of the cost and complications of esophagogastroduodenoscopy (EGD) are related to sedation. This study aimed to assess the feasibility, acceptability, and accuracy of unsedated small-caliber transoral EGD (sc-EGD). METHODS: A 4-phase study was performed in healthy volunteers and patients. Phases 1 and 2 involved assessment of the technical feasibility of sedated sc-EGD and the tolerability of unsedated sc-EGD, respectively, in volunteers. Subsequently, the technical feasibility, tolerability, and diagnostic accuracy of sedated and unsedated sc-EGD were determined by having each patient undergo sc-EGD (Pentax EG-1840) with (phase 3) and without (phase 4) sedation, followed by sedated conventional EGD (c-EGD) (Olympus GIF-100 or GIF-Q140) by a staff endoscopist blinded to the findings of the sc-EGD. The t test for paired samples was used for statistical analysis. A P value of <0.05 was considered significant. RESULTS: Sedated and unsedated sc-EGD were technically feasible and tolerable in all volunteers. In patients, compared with sedated c-EGD, sedated and unsedated sc-EGD were 96% and 97% accurate, respectively. The overall acceptability of unsedated sc-EGD was only slightly worse than that of sedated c-EGD (median, 2 vs. 1 on a scale of 1-10). After unsedated sc-EGD, 98% of patients expressed willingness to undergo the procedure again. No complications were observed during any phase of the study. CONCLUSIONS: Unsedated sc-EGD is technically feasible, tolerable, and accurate. It can potentially decrease the costs and complications of sedated conventional EGD.

Adult

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

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

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

[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

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

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

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

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

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

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

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