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Biomedical subjects

S Henry

Publications and source records attributed to S Henry.

At least 19 recordsLinked to original sources
PubMed2000

Molecular heterogeneity of the Jk(null) phenotype: expression analysis of the Jk(S291P) mutation found in Finns.

Polymerase chain reaction genotyping of 32 unrelated Jk(null) individuals originating predominantly from Polynesia and Finland indicated that all were homozygous for the JK*B polymorphism and that 17 of 32, including the 14 Polynesians, carried a 3'-acceptor splice site mutation of intron 5 that resulted in the skipping of exon 6 (called mutation Jk delta 6). The remaining 15 Jk(null) donors from Finland were homozygous for a new T871C transition resulting in a S291P amino acid substitution at a consensus N-glycosylation site of the Jk polypeptide. Transcription-translation assays revealed that the Jk(S291P) mutant was translated into a glycosylated component as efficiently as the wild-type Jk polypeptide (wt Jk)] in the presence of microsomes, thus indicating that the S291P mutation has no effect on the N-glycosylation pattern of the Jk protein. Expression studies in Xenopus oocytes revealed that the Jk(S291P) polypeptide functions as a urea transporter, but the transport activity and the membrane expression level of the mutant protein was reduced to a similar extent. A substantial fraction of the mutant protein was retained intracellularly suggesting that the transit to the plasma membrane was reduced, presumably because of the S-->P mutation. After transfection in erythroleukemia K562 cells the wild-type, but not the mutant, protein was efficiently expressed at the cell surface. Because the Jk(S291P) mutant polypeptide was not present in human red cells from Jk(null) individuals, expression data in the erythroid context clearly indicates that the S-->P mutation is the molecular basis of the Finnish Jk(null) phenotype. (Blood. 2000;96:1566-1573)

Finland↗
PubMed2000

Selective use of extracorporeal membrane oxygenation is warranted after lung transplantation.

OBJECTIVES: Early allograft dysfunction after lung transplantation ranges from subclinical x-ray abnormalities to pulmonary edema, hypoxemia, hypercarbia, and pulmonary hypertension. Management may include extracorporeal circulation to allow recovery of the acute lung injury. We reviewed our experience with extracorporeal membrane oxygenation after lung transplantation to assess the utility of this therapy. METHODS: A retrospective chart review was performed. Single or bilateral lung transplantation was performed in 444 adults from July 1988 to July 1998. Twelve (2.7%) patients experienced allograft dysfunction severe enough to require extracorporeal membrane oxygenation after failure of conventional therapy, including sedation, paralysis, and inhaled nitric oxide. RESULTS: Seven of 12 patients requiring extracorporeal membrane oxygenation were discharged from the hospital. Mean and median times to extracorporeal membrane oxygenation support were 1.2 days and 0 days, respectively. Mean length of support was 4.2 days. Four patients died while receiving extracorporeal membrane oxygenation support. One patient was weaned from extracorporeal membrane oxygenation but died during the hospitalization. Two patients required acute retransplantation while receiving extracorporeal membrane oxygenation, and one survived to discharge. Three patients continued to receive extracorporeal membrane oxygenation support for more than 4 days, and all 3 died. All survivors had begun receiving extracorporeal membrane oxygenation support by post-transplantation day 1. Three of 7 patients discharged from the hospital died 12 months, 13 months, and 72 months after transplantation because of bronchiolitis obliterans syndrome (n = 2) or lymphoma (n = 1). Four patients are alive 2, 12, 25, and 54 months after transplantation. CONCLUSIONS: Extracorporeal membrane oxygenation provides effective therapy for acute post-transplantation lung dysfunction. The frequency and pattern of our extracorporeal membrane oxygenation use reflects bias toward early extracorporeal membrane oxygenation support for isolated graft failure in otherwise intact and uninfected recipients.

Adult↗
PubMed2000

Human herpes virus 8 infection in kidney transplant patients in Belgium.

BACKGROUND: Kaposi sarcoma (KS) may arise as a complication of kidney transplantation. In the Saint Luc Teaching Hospital in Brussels, patients of both Belgian and foreign origin are treated. The prevalence of human herpes virus 8 (HHV-8) infection differs in different geographical settings. We wanted to estimate the background infection rate and the risk of infection in our transplant population: a first step towards evaluating the necessity of HHV-8 screening. METHODS: Serum samples were taken from 210 organ donors over a period of 7 years (30 per year) and from 200 kidney recipients from whom two sera were tested, one pre-transplant and the second 6-12 months post-transplant. All sera were screened for HHV-8 by an enzyme-linked immunosorbant assay using recombinant ORF 65 and ORF 73 antigens and an immunofluorescence assay for the latent antigen. Reactive samples were confirmed by western blotting. RESULTS: Seven donors (3.3%) were positive for HHV-8 antibodies. Of 198 pre-transplant sera available for evaluation, 15 were positive (7.6%). Post-transplantation 18/199 (9%) were positive: four (2.1% of negatives) had a documented seroconversion and one lost the antibodies. No patients developed KS. CONCLUSIONS: A substantial number of kidney transplant patients already had antibodies to HHV-8 at the time of transplantation. A further 2.1% of seronegative patients had seroconversion, which could have been acquired through the transplanted organ (3.3% of donors were positive) or through transfusion.

Antibodies, Viral↗
PubMed2000

Chemically modified oligonucleotides exhibit decreased immune stimulation in mice.

Phosphorothioate oligodeoxynucleotides produce splenomegaly and mononuclear cell infiltrates in multiple organs in mice after repeated i.v. administration. Several phosphorothioate oligodeoxynucleotides were studied to better understand the basis of immunostimulatory properties of these molecules in mice and to study the effects of chemically modified oligonucleotides. Chemical modifications examined included 5-methyl cytosine and 2'-methoxyethoxy substituents. Male mice (six per group) were treated with oligonucleotide concentrations of 0, 2, 10, or 50 mg/kg by i.v. injection every other day for 14 days. Immune stimulation was assessed 24 h after the last dose by measuring spleen weight, or histologic and immunohistochemical examination of liver and kidney. Immune stimulation was dose-dependent for the phosphorothioate oligodeoxynucleotides studied, but potency varied as a function of sequence. Results from this study reveal that there is a close correlation between the extent of splenomegaly and other evidence of immune stimulation, such as the severity of cell infiltrates in liver and kidney in mice. Immunohistochemical analysis indicated that cell infiltrates in liver and kidney were primarily mononuclear cells associated with increased expression of the endothelial-leukocyte cellular adhesion molecule intracellular adhesion molecule-1 and the cytokine interleukin-6. Immune stimulation was markedly decreased with oligonucleotides containing the 5-methyl cytosine and further decreased by 2'-methoxyethoxy modifications. Administration of these modified oligonucleotides to mice did not produce splenomegaly even at the 50-mg/kg dose, and only produced minimal cell infiltrates despite the presence of comparable or greater tissue oligonucleotide concentrations. Thus, chemical modifications appeared to increase the tolerability profile for these compounds that are representative of the second generation of antisense oligonucleotides.

Alanine Transaminase↗
PubMed1999

Malarial antibodies in Auckland blood donors.

AIM: To determine the malarial exposure characteristics of "malarial risk" blood donors and measure the potential infectivity of their donations using a commercially available malarial antibody screening kit. METHOD: Malarial risk donors were identified according to standard protocols, questioned as to their degree of exposure to malaria and blood samples were tested for malarial antibodies using an enzyme immunoassay kit. The kit used detects IgG antibodies to P. falciparum, shows 50% crossreactivity with P. vivax and some crossreactivity with P. ovale. Antibody positive samples were further checked by a direct immunochromatographic test for P. falciparum. RESULTS: We found 1.7% of the donors who were classified as a "malarial risk" to be positive for IgG malarial antibodies. None of these antibody positive samples was positive by the direct immunochromatographic test for P. falciparum. CONCLUSION: These results indicate that none of these donors tested were a risk of transmitting P. falciparum, the major and most serious cause of transfusion transmitted malaria. The introduction of malarial testing of malarial risk blood donors in Auckland, currently deferred for plasma donation only, could potentially recover 2300 units of red cells per year.

Animals↗
PubMed1999

Anatomical distribution of glycoprotein 93 (gp93) on nerve fibers during rat brain development.

Recent studies have implicated glycoconjugates on the membrane of growth cones as the necessary markers and intermediaries for axonal recognition, axonal motility, and pathway development. One such glycoconjugate, glycoprotein 93 (gp93), has been characterized, but the relative distribution of gp93 has yet to be described for the embryonic brain. In this study, the anatomical distribution of gp93 has been analyzed at embryonic day 15 (E15) and E18, and on postnatal day 3 in the rat by using a polyclonal gp93 antibody. Furthermore, fetal brain tissue transplanted into the adult rat eye has been tested for gp93 immunoreactivity, since central noradrenergic neurons in brainstem transplants are known to provide a continuous source of growing axons, even in adult tissue. In general, a greater abundance of gp93 immunoreactivity is apparent in the earlier embryonic stages (E15 and E18), whereas less is seen in the postnatal brain. The regions showing unique dispersal patterns of gp93 are the neuroepithelium, cerebral cortex, septo-hippocampal pathways, brainstem, and midbrain. This study has therefore focused on these areas and found implications for gp93 distribution appearing in the early development of specific neuronal pathways. Moreover, axons stain densely for gp93 within brain tissue transplants. The presence of gp93 in areas of extensive axonal outgrowth in the normal brain and in transplants suggests that this antibody is used as an early marker for axonal growth. Furthermore, gp93 might be used to map normal development in order to improve our understanding of diseases arising from developmental abnormalities.

Animals↗
PubMed1999

Resuscitation in the new millennium.

This article discusses resuscitation from a historical perspective; physiology; the optimal timing and volume for and fluids and endpoints of resuscitation; and the role of resuscitation in the future. Whether different types of victims of trauma should be resuscitated using different endpoints also is discussed.

Fluid Therapy↗
PubMed1999

Effects of glucagon in the control of endogenous glucose production in man.

Endogenous glucose production has been shown to increase during administration of glucagon + fructose, but not during administration of fructose alone. To determine the mechanisms by which glucagon exerts this action, endogenous glucose production (EGP) and gluconeogenesis from fructose (GNF) were measured in eight healthy subjects infused 1) with graded doses of glucagon (2 and 4 ng.kg-1.min-1 for 3 h each) during constant infusion of 13C-fructose (3 mg.kg-1.min-1), and 2) with graded doses of 13C-fructose (3 and 6 mg.kg-1.min-1) during constant glucagon infusion (2 ng.kg-1.min-1). GNF was estimated from 13C-glucose synthesis. In both protocols, infusion of 3 mg.kg-1.min-1 fructose + 2 ng.kg-1.min-1 glucagon increased EGP by 5-8% (P < 0.05), while GNF represented 43-49% of EGP. Thereafter, increasing the glucagon infusion rate further increased EGP to 118 +/- 3% of basal values (P < 0.01) without altering the proportion due to GNF. In contrast, increasing the fructose infusion rate at constant glucagonemia increased EGP similarly (by 19 +/- 4%, P < 0.05) but enhanced the contribution of GNF to 76 +/- 2% (P < 0.001). Graded infusion of glucagon or fructose alone failed to stimulate EGP. The present findings indicate that hyperglucagonemia stimulates endogenous glucose production during fructose infusion. This effect is not secondary to a stimulation of gluconeogenesis, but to a channelling of glucose-6-phosphate towards systemic release.

Adult↗
PubMed1999

Tuberculosis chemoprophylaxis using a liquid isoniazid-methadone admixture for drug users in methadone maintenance.

BACKGROUND: Tuberculosis is common in drug users, although compliance with therapy may be difficult in this population. OBJECTIVE: To evaluate an approach to enhancing compliance with tuberculosis chemoprophylaxis in drug users enrolled on methadone maintenance utilizing an isoniazid (INH)-methadone admixture. DESIGN: A prospective cohort study. SETTING: A drug treatment program in New Haven, Connecticut, USA. PATIENTS: Opioid-dependent drug users enrolled in methadone maintenance. INTERVENTION: Liquid isoniazid was mixed into subjects' daily dose of methadone. Vitamin B6 was given to subjects for self-administration. MEASUREMENTS AND MAIN RESULTS: Number of eligible subjects, reasons for not starting therapy, number starting therapy, proportion completing therapy and median duration of INH therapy were calculated. Thirty-nine subjects were eligible for INH chemoprophylaxis: 34 (87%) received INH mixed directly in their methadone and five (13%) had their INH consumption supervised by a nurse. Among these subjects, 72% (28/39) completed therapy. Among the 11 subjects who discontinued INH, discharge from the methadone maintenance program was the most common reason--73% (8/11). Thus, among the 31 subjects who were not discharged from methadone maintenance, 90% (28/31) successfully completed INH prophylaxis. The median duration of therapy was 182 days. CONCLUSIONS: Tuberculosis chemoprophylaxis using a liquid isoniazid-methadone admixture appears to be an effective approach to enhancing compliance with this therapy in methadone-maintained drug users.

Antitubercular Agents↗
PubMed1999

Sequence analysis and expression of a mRNA for a larval-specific cuticular protein, LCP1, from Helicoverpa armigera.

Several cDNA clones for a larval cuticular protein from Helicoverpa armigera were isolated and sequenced. The cDNA clones contain an open reading frame encoding a 109 residue protein which is homologous to other known cuticular proteins. The predicted protein appears to have a signal peptide which would be removed to give a mature protein of 91 amino acid residues with an Mr of 10 127. The mature protein, LCP1 (Larval Cuticular Protein), would be highly acidic, as is found for other cuticular proteins from flexible insect cuticles. The mRNA appears to be expressed throughout larval development although it is more highly expressed in the integument of the late final instar.

Amino Acid Sequence↗
PubMed1999

Cortical activation during human volitional swallowing: an event-related fMRI study.

Functional magnetic resonance imaging (fMRI) provides a safe, noninvasive method for studying task-related cortical neuronal activity. Because the cerebral cortex is strongly implicated in the control of human swallowing, we sought to identify its functional neuroanatomy using fMRI. In 10 healthy volunteers, a swallow event-related paradigm was performed by injecting 5 ml water bolus into the oral cavity every 30 s. Whole brain functional magnetic susceptibility -weighted spiral imaging data were simultaneously acquired over 600 s on a 1.5-T magnetic resonance scanner, utilizing the blood oxygenation level-dependent technique, and correlation maps were generated using both >99% percentile rank and spatial extent thresholding. We observed areas of increased signal change consistently in caudal sensorimotor cortex, anterior insula, premotor cortex, frontal operculum, anterior cingulate and prefrontal cortex, anterolateral and posterior parietal cortex, and precuneus and superiomedial temporal cortex. Less consistent activations were also seen in posterior cingulate cortex and putamen and caudate nuclei. Activations were bilateral, but almost every region, particularly the premotor, insular, and frontal opercular cortices, displayed lateralization to one or the other hemisphere. Swallow-related cortical activity is multidimensional, recruiting brain areas implicated in processing motor, sensory, and attention/affective aspects of the task.

Adult↗
PubMed1998

Microfabricated microneedles: a novel approach to transdermal drug delivery.

Although modern biotechnology has produced extremely sophisticated and potent drugs, many of these compounds cannot be effectively delivered using current drug delivery techniques (e.g., pills and injections). Transdermal delivery is an attractive alternative, but it is limited by the extremely low permeability of skin. Because the primary barrier to transport is located in the upper 10-15 micron of skin and nerves are found only in deeper tissue, we used a reactive ion etching microfabrication technique to make arrays of microneedles long enough to cross the permeability barrier but not so long that they stimulate nerves, thereby potentially causing no pain. These microneedle arrays could be easily inserted into skin without breaking and were shown to increase permeability of human skin in vitro to a model drug, calcein, by up to 4 orders of magnitude. Limited tests on human subjects indicated that microneedles were reported as painless. This paper describes the first published study on the use of microfabricated microneedles to enhance drug delivery across skin.

Administration, Cutaneous↗
PubMed1998

IgG subclass distribution of antibody responses to protein and polysaccharide mycobacterial antigens in leprosy and tuberculosis patients.

Immunoenzymatic assays were developed for the measurement of antibodies against mycobacterial lipoarabinomannan (LAM), a cell-free proteic extract (CFX) of Mycobacterium leprae, and the 38-kD protein antigen of M. tuberculosis. Sera from 108 leprosy patients, belonging to all clinical-immunological forms of the spectrum, and 81 patients with localized or disseminated tuberculosis (TB) were tested for antibodies of the four IgG subclasses. Standard calibration curves were used to allow comparisons between results of different isotypes and specificities. Mean concentrations of total IgG antibodies were higher in the overall leprosy population than in TB patients. In leprosy, levels of anti-CFX increased from tuberculoid toward lepromatous forms, with a clear switch from IgG1 to IgG2 subclass predominance. A similar IgG1 to IgG2 conversion was observed in anti-LAM antibodies, although total levels of anti-LAM were similar in patients with tuberculoid and lepromatous forms. In TB, antibodies against polysaccharide and protein antigens were both predominantly of IgG1 subclass, whatever the patient's clinical status, although lower in disseminated forms, probably due to concomitant HIV infection. A hypergammaglobulinaemia was also found in most leprosy and TB patients. In TB this was due to increased IgG1 and IgG3, especially in HIV co-infected patients. Based on the current knowledge of the influence of T cell-secreted cytokines on human immunoglobulin isotype expression, these results do not fit with a putative role of Th1 (such as found in TB and tuberculoid leprosy (TT)) and Th2 (such as found in leprosy lepromatous (LL) leprosy) environment in the isotypy of antibody responses in mycobacterial infections. Nor do variations of isotypy according to pathological conditions seem to be related to the biochemical nature of antigens, since antibodies to LAM and protein antigens had comparable evolutions of their subclass distribution. Other factors are to be investigated in order to understand better the significance and possible roles of antibodies in mycobacterial diseases.

Adolescent↗
PubMed1998

Effects of a sympathetic activation by a lower body negative pressure on glucose and lipid metabolism.

The effects of a sympathetic activation elicited by a lower body negative pressure (LBNP) (at -15 mmHg for 75 min) were assessed in 7 healthy subjects on two occasions: (i) in post-absorptive conditions, and (ii) during glucose infusion (22.2 mumol kg-1 min-1). LBNP increased plasma norepinephrine concentration and heart rate. It did not alter whole-body glucose metabolism (measured with [6,6-2H]glucose) and glycerol turnover (measured with [1,1,2,3,3-2H]glycerol). Interstitial glycerol concentrations were monitored with microdialysis in subcutaneous adipose tissue and in skeletal muscle. LBNP increased dialysate glycerol concentrations in muscle by 16% (P < 0.03) but not in adipose tissue in post-absorptive conditions, and by 37% in adipose tissue (P < 0.05) but not in muscle during glucose infusion. These results indicate that an LBNP-induced sympathetic activation (i) does not increase endogenous glucose production, and (ii) induces only a slight stimulation of lipolysis in adipose tissue during glucose infusion.

Adolescent↗
PubMed1998

Point mutations and deletion responsible for the Bombay H null and the Reunion H weak blood groups.

OBJECTIVE: Definition of the molecular basis of the Reunion and the Bombay red cell and salivary H-deficient phenotypes. METHODS: Sequence and expression of FUT1 and FUT2 genes from H-deficient individuals. Family segregation analysis of the mutations responsible for the fucosyltransferase defects of H, secretor and Lewis systems. RESULTS: The Indian red cell H null Bombay phenotype depends on a new mutation of the FUT1 gene. T725-->G changing Leu242-->Arg. Their salivary nonsecretor phenotype is secondary to a complete deletion of the FUT2 gene. The red cell H weak Reunion phenotype depends on another new mutation of FUT1, C349-->T which induces a change of His117-->Tyr. Their salivary nonsecretor phenotype is due to the known Caucasian inactivating mutation G428-->A. CONCLUSION: Single prevalent FUT1 and FUT2 point mutations and a deletion are responsible for the Indian Bombay H null and the Reunion H weak phenotypes found on Reunion island. This is in contrast with other H-deficient phenotypes where sporadic nonprevalent inactivating mutations are the rule.

ABO Blood-Group System↗
PubMed1998

[Direct diagnosis of Chlamydia trachomatis genital infections: culture or PCR?].

PCR and culturing were compared for the routine diagnosis of Chlamydia trachomatis infections. Two laboratories experienced in both techniques participated in the study, which included 513 specimens. Both techniques were performed on each specimen; the portion of the specimen used for PCR was divided in two, and each half was sent to one of the two laboratories, where the tests were run in a blinded fashion. The PCR primers used by the two laboratories matched different parts of the bacterial genome. PCR inhibitors were looked for in all specimens. Overall, PCR was more sensitive than culturing; the difference was marked for sperm and endopelvic specimens and nonsignificant for urethral and cervical specimens. False-positive PCR results were few in number; there were no consistent false-positive results when each specimen was amplified twice. PCR inhibitors were rarely present in urethral and cervical specimens but were found in 7% of sperm and endopelvic specimens. PCR inhibitors should be looked for routinely during PCR testing of sperm or endopelvic specimens.

Bacteriological Techniques↗