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Biomedical subjects

H M Smith

Publications and source records attributed to H M Smith.

At least 37 records · Page 2Linked to original sources

Lower extremity injuries in in-line skaters: a report of two cases.

In-line skating has become a very popular sport over the past several years. Previous studies examining the injuries associated with this sport have emphasized the incidence upper extremity injuries. Two cases are described in which patients suffered severe lower extremity injuries while in-line skating: one had a femoral shaft spiral fracture and the other bilateral anterior cruciate ligament and medial collateral ligament injuries. Although a predominance of upper extremity injuries associated with this sport has been widely noted, increased numbers of participants, higher speeds and changing skate designs may further predispose skaters to leg, knee and ankle injuries.

Adult↗

Quantitative assessment of serum beta-2-microglobulin in liver transplant recipients and relationship to liver graft rejection.

OBJECTIVE: To investigate the usefulness of serum beta 2-microglobulin determination in the diagnosis of acute liver allograft rejection. DESIGN: Prospective study. SETTING: Liver transplant unit. PATIENTS: Twenty consecutive patients who underwent liver transplantation because of a non-virus-related end-stage liver disease. METHODS: Serum samples were collected before the transplant, at days 7, 30 and 90 and whenever a clinical complication developed after liver transplantation. beta 2-Microglobulin was quantified using a new quantitative automated microparticle enzyme immunoassay. RESULTS: Serum beta 2-microglobulin levels increased significantly (P < 0.05) during rejection episodes and correlated with the degree of hepatocyte injury as assessed using serum aspartate aminotransferase levels. Increased beta 2-microglobulin levels were also found in surgical or infectious post-transplant complications. A significant difference in beta 2-microglobulin values was recorded between patients with rejection and only those with bacterial sepsis. CONCLUSION: Although highly sensitive in recognizing damage to the graft, determination of beta 2-microglobulin was not sufficiently specific to differentiate between rejection and other post-transplantation complications.

Adult↗

Three classes of nuclear import signals bind to plant nuclei.

Three nuclear localization signals (NLS), including an unusual Mat alpha 2-like NLS from maize (Zea mays) R, were found to compete for binding to plant nuclei. In addition, the authentic yeast Mat alpha 2 NLS, which does not function in mammals, was shown to function in plants in vivo. Our results indicate that plants possess a site at the nuclear pore complex that recognizes the three known classes of NLSs.

Amino Acid Sequence↗

Autoimmune mechanisms in chronic hepatitis B and delta virus infections.

OBJECTIVE: To investigate the possibility that hepatitis delta virus infection may be responsible for, or enhance, the autoreactivity seen in patients chronically infected with hepatitis B virus. DESIGN: Sera from 68 patients with chronic hepatitis B infection, 27 of whom had concomitant delta virus (HDV) infection and 19 of whom were infected with hepatitis C virus (HCV), were screened for (1) the non-organ-specific autoantibodies usually associated with autoimmune hepatitis, (2) antibodies against the putative autoantigen, GOR, which have been described in patients with HCV infection and (3) antibodies against a hepatocyte-specific autoantigen, the asialoglycoprotein receptor (ASGP-R). METHODS: Anti-GOR antibodies were detected using an enzyme-linked immunosorbent assay against a synthetic GOR peptide, non-organ-specific autoantibodies using standard indirect immunofluorescence and anti-ASGP-R antibodies using a radioimmunoassay. RESULTS: Liver-specific autoreactivity, manifested by circulating anti-ASGP-R antibodies, was found in 41 (60.3%) patients and correlated independently with the histological severity of liver damage but not with HDV infection. In contrast, non-organ-specific autoantibodies (antinuclear, anti-smooth muscle, anti-gastric parietal cell and anti-liver-kidney microsomal type 1) were found (mostly at low titres) in only 15 (22.1%) patients and did not correlate with either HDV infection or with histological severity. Basal cell layer antibodies and type 3 liver-kidney microsomal antibodies were not seen in any patient. Antibodies against GOR were found in only five (7.4%) patients, all of whom showed evidence of exposure to HCV. CONCLUSION: The findings suggest that HBV-induced liver-specific autoreactions might contribute to periportal liver damage in patients with chronic hepatitis B infection, but do not support the notion that the delta virus can induce an autoimmune response or that HCV coinfection suppresses autoreactivity in this situation.

Adult↗

Impact of immunoprophylaxis and patient selection on outcome of transplantation for HBsAg-positive liver recipients.

We have studied the roles of immunoprophylaxis, patient selection policy and coexistent hepatitis D virus infection in the outcome of 56 HBsAg-positive elective liver transplant recipients. Twenty-nine unselected patients not treated with immunoprophylaxis formed group 1 and were compared to a recent consecutive series of 27 patients (group 2) in whom pre-transplant serological status was determined and who received immunoprophylaxis. One-year actuarial HBsAg serological recurrence rates were 48% in group 2 and 90% in group 1 with particular improvement in recipients who were either HBV DNA-negative or who had co-existent hepatitis delta virus infection. One-year patient survival has improved from 62% in group 1 to 86% in group 2 with improvements in hepatitis delta virus-negative and replicating recipients. Patients who have either co-existent hepatitis delta virus infection or are in group 2 have 1-year survival rates comparable to elective HBsAg-negative recipients (19/21 (90%), 22/27 (86%) vs 87%, respectively). In the event of recurrence, severe graft injury is diminished in recent patients and in those with coexistent delta infection who also have lower levels of circulating HBV DNA. Retransplantation for associated graft injury has a poor prognosis irrespective of administration of immunoprophylaxis. In elective liver recipients, immunoprophylaxis and/or hepatitis delta virus infection modulate hepatitis B virus recurrence and associated graft injury with consequent improvement in patient survival.

Adult↗

Tissue-specific expression of the human CD19 gene in transgenic mice inhibits antigen-independent B-lymphocyte development.

CD19 is a B-cell-specific member of the immunoglobulin superfamily expressed from early pre-B-cell development until plasma cell differentiation. In vitro studies demonstrate that the CD19 signal transduction molecule can serve as a costimulatory molecule for activation through other B-lymphocyte cell surface molecules. However, much remains to be known regarding how CD19 functions in vivo and whether CD19 has different roles at particular stages of B-cell differentiation. Therefore, transgenic mice overexpressing the human CD19 (hCD19) gene were generated to determine whether this transgene would be expressed in a B-lineage-specific fashion and to dissect the in vivo role of CD19 in B-cell development and activation. Expression of the human transgene product was specifically restricted to all B-lineage cells and appeared early in development as occurs with hCD19. In addition, expression of hCD19 severely impaired the development of immature B cells in the bone marrow, with dramatically fewer B cells found in the spleen, peripheral circulation, and peritoneal cavity. The level of hCD19 expressed on the cell surface correlated directly with the severity of the defect in different transgenic lines. These results demonstrate that the hCD19 gene is expressed in a lineage-specific fashion in mice, indicating that the hCD19 gene may be useful for mediating B-lineage-specific expression of other transgene products. In addition, these results indicate an important role for the lineage-specific CD19 molecule during early B-cell development before antigen-dependent activation.

Aging↗

Outcome of renal transplantation in hepatitis BsAg-positive patients.

Renal transplantation of patients with previous or ongoing hepatitis B virus infection has been tempered with a concern that immunosuppression may lead to viral replication and progressive liver damage. However, renal transplantation as therapy for end-stage renal failure in these patients improves quality of life and reduces the risk of body fluid exposure to their carers. To assess the long-term outcome of renal transplantation in hepatitis-BsAg-positive patients a retrospective study was carried out on the patients transplanted in this unit since 1969. Seventy-six patients received 98 grafts up to December 1991; follow-up was available on 68. Thirty-one of the 68 patients died; the causes of death were infective 23, cardiovascular 6, liver failure 4, pancreatitis 2, aspiration 1, GI haemorrhage 1, and stopped therapy 1. Serological markers of hepatitis B virus infection did not correlate with outcome. The risk of developing liver failure after renal transplantation appears small in the hepatitis-BsAg-positive patients and no patient should be denied a renal transplant on the basis of serological tests.

Adolescent↗

Quantitative assessment of serum IgM anti-HBc in the natural course and during interferon treatment of chronic hepatitis B virus infection.

Serum IgM anti-HBc was determined in 135 chronic HBsAg carriers with various categories of histological activity on liver biopsy and hepatitis B serological profile. Thirty-three patients were treated with interferon-alpha to investigate the correlation between serum IgM anti-HBc with histological activity and viral replication, to evaluate the usefulness of pretreatment IgM anti-HBc as a predictor of a successful response to interferon-alpha and to examine the IgM anti-HBc response during this treatment. All 53 patients with chronic active hepatitis with either wild-type (n = 42) or precore mutant variant HBV infection (n = 11) had an IgM anti-HBc index greater than 0.300 compared with 7.4% (2 of 27) of the chronic HBsAg/HBeAg-positive carriers with chronic persistent hepatitis, 10% (3 of 30) of the anti-HBe-positive asymptomatic carriers and none of the 25 patients with hepatitis D virus-positive chronic active hepatitis (p < 0.0001). Pretreatment IgM anti-HBc index was greater than 0.300 in 82.4% (14 of 17) of HBeAg/HBV DNA-positive patients who seroconverted after interferon-alpha treatment compared with 25% (4 of 16) of the patients who did not seroconvert (p = 0.0013), whereas an elevated pretreatment AST was present in only 52.9% (9 of 17) of responders and in 37.5% (6 of 16) of nonresponders (p = 0.42). Serial testing of IgM anti-HBc in these 33 patients during interferon-alpha treatment showed a significant rise in IgM anti-HBc in all responders, which followed the AST flare-up but preceded the time of the HBeAg to anti-HBe seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspartate Aminotransferases↗

Reptilian and avian ovarian cycles and the evolutionary origin of volant birds.

The first birds probably evolved from a line of theropod dinosaurs in the late Jurassic or early Cretaceous. The "trees down" theory proposes that avian ancestors were arboreal, whereas the "ground-up" (cursorial) theory suggests that they were terrestrial, and ran and jumped for prey. We present suggestive evidence from reptilian and avian female reproductive biology that supports the arboreal theory, although neontological evidence can never authenticate a paleontological event. The "law of follicular constancy" is an empirical observation that the number of ovulations per female per ovulatory cycle (instantaneous fecundity, or IF) is the same regardless of the amount of ovarian tissue present. In vertebrates with an IF of two or more, surgical removal of one of the paired ovaries (unilateral ovariectomy, or ULO) leads to a doubling of ovulations from the remaining ovary (compensatory ovarian hypertrophy, or COH), this ovary cycling at the same frequency as it did before surgery. In vertebrates that produce one egg alternately from each ovary (an IF of one), however, ULO leads to a form of COH in which the remaining ovary still ovulates one egg at a time but twice as frequently. In most birds, only the left ovary is present; it ovulates a single egg every 1-2 days until the species-specific clutch size is reached. Inasmuch as this avian ovulatory pattern is similar to an accelerated version of that occurring after ULO in a species that alternates ovulation, we propose that birds evolved from dinosaurs with such a pattern. A great majority of extant reptiles with an IF of one are either anoline or gekkonid lizards, and many of these ovulate several times a year. Furthermore, most species in these tropical groups are arboreal. Even considering phylogenetic constraints within anoline and gekkonid lizards, we propose that correlations of arboreality and an IF of one in these groups are implied as adaptive relationships and represent ecological parallelisms. Therefore, we propose that the ancestors of birds were arboreal. Furthermore, they probably were of small size, as are all lizards with an IF of one.

Animals↗

Loss of HBsAg with interferon-alpha therapy in chronic hepatitis D virus infection.

Eleven patients with chronic hepatitis D virus (HDV) infection who had chronic active hepatitis and HDV antigen on liver biopsy were randomised in a crossover therapeutic trial of interferon-alpha 2b vs. no therapy. Nine patients had a history of intravenous drug use (drug free > 6 months before therapy), 8 had histological evidence of cirrhosis, and 7 out of 10 tested were found to be seropositive for antibody to hepatitis C virus (HCV). Six patients were randomised to receive interferon-alpha 2b therapy for 1 year, and 5 patients received no therapy for 1 year followed by the same regime of interferon-alpha 2b treatment. All patients with a history of intravenous drug use found self-injection stressful, 3 patients restarted using illicit drugs, and 2 patients with active cirrhosis developed severe thrombocytopenia during therapy and treatment was stopped in these patients. Of the 6 patients who completed at least 11 months of treatment, 4 lost serum hepatitis B surface antigen (HBsAg) with 3 developing antibody to HBsAg and one patient completing treatment. Among the 6 patients who had posttreatment liver biopsy, 5 showed an improvement in liver histology (3 of them lost serum HBsAg). These results provide further evidence that interferon-alpha is beneficial in chronic HDV infection although the psychological stress associated with the treatment, especially in patients with a previous history of intravenous drug use, is not inconceivable.

Adult↗

Prairie rattlesnakes (Crotalus viridis) respond to rodent blood with chemosensory searching.

In Experiment I, homogenized rodent tissue was applied to the lips of prairie rattlesnakes (Crotalus viridis). This treatment produced elevated rates of tongue flicking compared to controls that received water, but the elevations seen following stimulation with homogenate were not as large as those seen after snakes struck prey. In Experiment II, water, rodent blood, and integumentary cues were applied to the lips of rattlesnakes, and only blood resulted in elevated rates of tongue flicking. We conclude that blood is a critical component of the homogenate. It is hypothesized that detection of blood during predatory strikes may be a causal element in the triggering of strike-induced chemosensory searching, a typical component of rattlesnake predatory behavior.

Animals↗

A novel cell-surface molecule expressed by human interdigitating reticulum cells, Langerhans cells, and activated lymphocytes is a new member of the Ig superfamily.

cDNA isolated from a human lymphocyte library were analyzed and shown to encode a novel cell-surface glycoprotein, termed HB15, expressed by dendritic cell subsets and activated lymphocytes. The predicted mature 186 amino acid protein was composed of a single extracellular V-type Ig-like domain, a transmembrane region, and a 39-amino acid cytoplasmic domain. In contrast to most Ig-like domains, analysis of a partial genomic DNA clone revealed that the extracellular Ig-like domain of HB15 was encoded by at least two exons. Northern blot analysis revealed that HB15 derived from three mRNA transcripts of approximately 1.7, 2.0, and 2.5 kb expressed by lymphoblastoid cell lines. Two mAb reactive with HB15 were produced and used to show that HB15 is expressed as a single chain cell-surface glycoprotein of M(r) 45,000. HB15 expression was specific for lymphoblastoid cell lines and mitogen-activated lymphocytes, and HB15 was not expressed at detectable levels by circulating leukocytes. Immunohistologic analysis revealed that HB15 had a unique pattern of expression, being found predominantly in hemopoietic tissues with strong expression by scattered interfollicular interdigitating reticulum cells and weak expression by germinal center cells. HB15 was also expressed by Langerhans cells within the skin. HB15 therefore serves as a unique marker for the subset of dendritic cells represented by Langerhans cells and interdigitating reticulum cells. Thus, the HB15 glycoprotein represents a newly identified member of the Ig superfamily that may play a significant role in Ag presentation or the cellular interactions that follow lymphocyte activation.

Amino Acid Sequence↗

Significance of serum IgM anti-HBc in chronic hepatitis B virus infection.

Because of widely differing reports on the significance of IgM anti-HBc in chronic hepatitis B virus (HBV) infection, paired sera and liver biopsies from 49 patients with chronic HBV infection were analysed for serum IgM anti-HBc, HBsAg titre, HBeAg/anti-HBe, HBV DNA, serum aspartate transaminase, intrahepatic HBcAg expression, and liver histology. High levels of IgM anti-HBc, in the diagnostic range of acute hepatitis B (greater than 1.2), were detected in seven patients (14.3%) and a total of 34 patients (69.6%) had an index of more than 0.2. No correlation was found between IgM anti-HBc and the serum markers of active viral replication or HBsAg titre but it correlated significantly with intrahepatic expression of cytoplasmic HBcAg (r2 = 0.165, P = 0.002). IgM anti-HBc also correlated with active liver histology (P = 0.015) but there was a considerable overlap of the IgM anti-HBc index values between the various disease groups, indicating a poor specificity. Serial assessment of IgM anti-HBc in eight patients treated with interferon-alpha (four responders) showed an increase in IgM anti-HBc in three out of four patients corresponding to the e-seroconversion period followed by a drop in IgM anti-HBc levels. However, an increase in IgM anti-HBc was also seen in one non-responder, indicating that this feature is not unique to interferon-alpha responders. These data indicate that serum IgM anti-HBc cannot be used alone as a certain diagnostic measure of HBV replication nor in the prediction of liver histology.

Adolescent↗

Toga virus-like particles in acute liver failure attributed to sporadic non-A, non-B hepatitis and recurrence after liver transplantation.

Toga virus-like particles (typically 60-70 nm: enveloped with small surface spikes) were detected in the native hepatectomy specimens in 7 of 18 patients grafted for acute liver failure attributed to sporadic non-A, non-B hepatitis and in 2 patients grafted for fulminant hepatitis attributed to anti-epileptic drug hepatotoxicity. These particles were not detected in the hepatectomies from 12 other patients grafted for other causes of acute liver failure, 12 for various chronic liver diseases, and 2 histologically normal livers. Acute hepatic failure, characterized histologically by severe haemorrhagic necrosis, developed 7 days after grafting in 5 patients, all in the non-A, non-B group with toga virus-like particles in native liver. Similar virus-like particles were detected in all grafts and were in greater abundance than in the native livers. The agent may be novel because pre- and post-grafting sera were negative for antibodies against representative panels of arboviruses and in first and second generation antibody tests for hepatitis C virus.

Adolescent↗

Stimulus control of predatory behavior in the brown tree snake (Boiga irregularis). IV. Effect of mammalian blood.

Brown tree snakes (Boiga irregularis) from Guam were exposed to mammalian (Rattus norvegicus) blood on cotton-tipped applicators. Water and other control substances were similarly presented. All trials lasted 60 s, and the dependent variable was the number of tongue flicks emitted by the snake during the trial. In five experiments, B. irregularis responded with greater numbers of tongue flicks to blood than to control substances. This is the first study to reveal an ophidian response to internal chemicals of potential prey organisms.

Amniotic Fluid↗

Hepatitis B virus reinfection after orthotopic liver transplantation. Serological and clinical implications.

The implications of hepatitis B virus (HBV) reinfection after liver transplantation were studied in 29 patients followed for 1.7-15 years. Of 20 patients with HBV infection alone, nine were HBeAg and HBV DNA seronegative and 11 had evidence of HBV replication as measured by HBeAg or HBV DNA seropositivity. Nine patients had co-existing HBV and delta virus (HDV) infection. Five patients became HBsAg seronegative after transplantation (four immediately and one after an hepatitic episode). Of the 20 patients with HBV infection alone, 17 had evidence of viral replication after transplantation with markedly increased HBV DNA levels. Five patients with HDV infection had HBV DNA in serum, but in significantly lower amounts than in those with HBV infection alone. Twenty-five episodes of graft dysfunction attributed to recurrent HBV infection occurred in 19 patients (65.5%). Thirteen episodes (in 12 patients) were self-resolving acute hepatitic illnesses. Six patients had a rapidly progressive illness leading to graft loss within 6 weeks, with the distinctive histological features termed fibrosing cholestatic hepatitis (FCH). Liver function tests in these patients showed markedly abnormal serum bilirubin and prothrombin times, but only modest increases in serum transaminase levels. An additional six patients lost their graft as a consequence of HBV recurrence through various pathogenetic mechanisms including possible (but unproven) FCH, chronic active hepatitis or late-onset hepatic failure. Co-existing HDV infection appeared to confer some medium-term protection from graft loss.

Adult↗