Biomedical subjects
Publications and source records attributed to W L Chan.
We study the large time behaviour of a nonlinear population model with a general logistic term. It is proved that every solution must have a limit when time becomes infinite. We present conditions that guarantee the boundedness of the solution. Furthermore, we prove that in general no oscillation is possible for the total number of population. This is in sharp contrast to the linear case.
Thirteen patients in chronic atrial fibrillation with a normal resting heart rate but with exercise tachycardia and episodes of bradycardia were randomised to treatment periods of two weeks on xamoterol (200 mg twice daily), low dose digoxin, or placebo, in a blind crossover study. The results (mean SEM) of symptom scores, a treadmill exercise test, and 24 hour ambulatory electrocardiographic monitoring were obtained. Xamoterol improved symptom scores and controlled exercise heart rate better than digoxin. Xamoterol was better than digoxin or placebo in reducing the heart rate response to exercise and tended to improve exercise duration. Xamoterol, by reducing the daytime maximum hourly heart rate and increasing the night time minimum hourly heart rate, significantly reduced the difference between the two compared with placebo. In contrast, digoxin tended to reduce both the maximum and minimum hourly heart rates through day and night. Both the frequency and duration of ventricular pauses were reduced by xamoterol but tended to increase with digoxin. Xamoterol reduced both the circadian variation in ventricular response to atrial fibrillation and exercise tachycardia by modulating the heart rate according to the prevailing level of sympathetic activity. These changes were translated into symptomatic benefit for the patients studied.
Evidence presented here from kinetic studies of interleukin-3 (IL-3) production by spleen cells from adult mice infected subcutaneously with HSV-1 and stimulated with virus antigen in vitro shows that high levels of IL-3 were produced at the onset of the animal's recovery from the disease state. Injections of anti-IL-3 antibody into HSV-1-infected mice resulted in exacerbation of the disease. Primary mouse embryonic head cells grown in the presence of murine IL-3, when infected with HSV-1, showed a 1000-fold decrease in virus titre compared with untreated control cells. This inhibiting effect was reversed by anti-IL-3 and anti-IFN-alpha, beta and gamma antibodies. These data suggest that IL-3 plays a host-protective role against HSV infection and it does so probably by inducing brain cells to produce interferons which then inhibit virus replication.
BALB/c mice are highly susceptible to Leishmania major infection. They develop a progressive fatal disseminating disease even with a minimum infecting dose. However, these mice are able to contain the disease if they are exposed to sublethal gamma-irradiation shortly before infection. Earlier studies demonstrated that CD4+ T cells from mice which had recovered from infection (Tr) can adoptively transfer resistance. In contrast, CD4+ cells from mice with progressive disease (Ts) not only failed to protect, but can reverse the protective effect of the Tr cells. Spleen cells from BALB/c mice which had recovered from L. major infection or which had progressive disease were cultured with leishmanial antigens in vitro. The culture supernatant from spleen cells of recovered mice (TrSN) contains high levels of macrophage-activating factor (MAF) activity which can activate peritoneal macrophages to kill 51Cr-labeled P815 cells and to eliminate intracellular parasites as measured by the reduction in [3H]thymidine uptake by residual parasites released from macrophages following sodium dodecyl sulfate treatment. The MAF activity of TrSN parallels that of recombinant interferon-gamma (IFN-gamma). In contrast, culture supernatant of spleen cells from mice with progressive disease (TsSN) contains no detectable MAF but it is able to neutralize the MAF activity of TrSN. The MAF-inhibiting function of TsSN appears to be mediated by interleukin (IL)3 and IL4, since the MAF activity of TrSN and rIFN-gamma also can be inhibited by the addition of rIL3 and rIL4 but not by rIL1 or rIL2. Furthermore, the MAF-inhibiting activity of TsSN can be partially reversed by the addition of specific anti-IL3 or anti-IL4, but completely reversed by the combination of the two antibodies in vitro. These findings provide a mechanism for the immune regulation in leishmaniasis and a means by which the two subsets of CD4+ T cells influence each other through their modulation of macrophage function.
The authors studied optimal birth control policies for an age-structured population of McKendrick type which is a distributed parameter system involving 1st order partial differential equations with nonlocal bilinear boundary control. The functional analytic approach of Dubovitskii and Milyutin is adopted in the investigation. Maximum principles for problems with a free end condition and fixed final horizon are developed, and the time optimal control problems, the problem with target sets, and infinite planning horizon case are investigated.
Herpes simplex virus (HSV) infection of mice can induce viral encephalitis. Using two-fluorochrome immunofluorescence, our present study shows that though there is extensive myelin loss and necrosis in the brain stem of mice with HSV encephalitis, only some oligodendrocytes, astrocytes and microglial cells are infected. T cells that express CD4 or CD8 and a large number of CD4+, F4/80+ macrophages are present in perivascular infiltrates close to and in contact with HSV-infected cells in areas of massive myelin loss. These findings suggest that the resultant infiltration of immune cells into the brain during HSV-1 infection may cause as much damage as the virus itself.
A monoclonal antibody (T157) directed against gB-1, the glycoprotein B (gB) of herpes simplex virus-1 (HSV-1) shows positive indirect immunoflourescent staining with an Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line B95-8. SDS PAGE and Western blot analysis show that B95-8 cells contain a 110,000 MW protein that co-migrates with the 110,000-115,000 MW gB-1. The gB-1 homologue of EBV (gB-EBV), immunopurified using a T157 affinity column, cross-stimulates HSV-1 immune T cells to proliferate in vitro. Mice immunized by a single subcutaneous injection of 30 microg gB-EBV in saline developed significant protection against HSV-1 challenge infection. Therefore gB-EBV can be considered a potential candidate vaccine and as an antigen to examine the cell-mediated immune response mounted by the host to limit virus spread during productive infection. The significance of a better understanding of the immune response to this and other EBV proteins of productive infection as an alternative to limit tumour growth by preventing virus spread is discussed.
UNLABELLED: Recombinant tissue plasminogen activator (rt-PA) is the most promising agent use for salvaging ischemic myocardium in acute infarction. To assess the safety and efficacy of rt-PA thrombolytic therapy, an open label clinical trial was conducted. Patients of acute myocardial infarction with angina, occurring within the five previous hours, was treated with rt-PA 100 mg infusion within three hours; followed with coronary arteriography to assess the patency rate of infarct vessels. Twenty-five cases of acute myocardial infarction were studied over a 10-month period. The patients, 24 male and one female, were aged 58.1 +/- 7.7 years. Rt-PA was given at 3.17 +/- 1.0 hour. Infarct-related vessels had opened in 21/24 cases when examined with coronary arteriogram three hours after infusion. Good antegrade flow of grade 2 to 3 was gained in 20/24 cases, representing an 83% success rate. One patient expired from cardiogenic shock during the infusion; another was expired from noncardiac accident after coronary bypass graft. The total inhospital mortality rate was about 8%. There was no major bleeding complication except in one case with gastrointestinal bleeding requiring transfusion. IN CONCLUSION: rt-PA is safe and effective in the treatment of acute myocardial infarction in the early stage. Coronary arteriography can be safely delayed until three hours postinfusion, and the achieved reperfusion rate is up to 83%.
Oligopeptides of the highly conserved herpes virus glycoprotein B (gB) were expressed from DNA fragments of the EBV gB (BALF4) and HSV-2 gB open reading frames as fusion proteins with the lambda CII protein and beta-galactosidase (GZ), respectively, in Escherichia coli. After immunopurification using anti-gB or anti-GZ affinity columns, the fusion proteins were used in vitro to stimulate human peripheral blood lymphocytes (PBL) or murine lymph node cells that have been primed with EBV, HSV-1, HSV-2, VZV or HCMV (all human herpes viruses) to proliferate. Results obtained in BALB/c mice indicate that different herpes viruses induce different levels of T-cell response to each other and to gB, over a range of type-specific and cross-reactive T-cell epitopes. There is a lack of correlation of immunogenicity and antigenicity in the generation of T-cell responses between some of the viruses. Major T-cell epitopes are located at the C terminal half of the gB molecule. The T-cell response to gB in healthy individuals seropositive for various combinations of the five herpes viruses differed markedly from individual to individual, even when they are seropositive to the same set of herpes viruses. However, two individuals with high proliferative T-cell response to VZV and sharing HLA A2, B7, DR2 and DQw1 are also good responders for cross-reactive gB/fragments and for virus antigen of all the five herpes viruses. Therefore the data obtained demonstrated that the MHC and the immune interaction arising from cross-reactive T-cell response evoked by other herpes viruses may determine the pathogenesis of a herpes virus infection.
Massive endocardial calcific deposits in the left ventricular chamber is such an uncommon lesion that only three cases have been reported previously. This report describes an apparently asymptomatic patient with endomyocardial fibrosis and massive endocardial calcific deposits. The results of electrocardiography, echocardiography, angiography, and endomyocardial biopsy findings are presented, and the pathogenesis of massive endocardial calcification is speculated upon. The interesting point is that the clinical history and manifestation of this patient suggests that endomyocardial fibrosis may occur in a benign form and long-term survival may be expected.
1. A monoclonal antibody (TG7A) reacts with a Mr 90,000 mammalian protein, accumulating during virus infection and heat shock. 2. This protein is encoded by a member of the Mr 90,000 heat shock gene family present in a range of organisms form yeast to man. 3. The antibody also recognises a Mr 94,000 protein in E. coli which similarly accumulates in virus infection and heat shock. 4. This protein has been identified as the Lon protease of E. coli. 5. The shared epitope and similar stress inducibility of the two proteins suggests that a functional and/or evolutionary relationship exists between them.
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A small number of cellular proteins accumulate to high levels in cells infected with Herpes Simplex Virus (HSV) despite a generalised repression of most host cell bio-synthesis. An antibody to one such protein has been used to screen a lambda gt11 library and for polysome immunoprecipitation in order to isolate cDNA clones derived from the corresponding gene. The cDNA clones have been used in dot blot and nuclear run-off assays to show that HSV, like other DNA tumour viruses can transcriptionally induce a cellular gene. The mechanism of this effect which is dependent on viral protein synthesis and its possible significance in transformation by HSV are discussed.
The type specificity of 16 herpes simplex monoclonal antibodies was tested on 50 isolates previously typed by endonuclease restriction. A panel of antibodies was selected and used to type isolates from 50 primary and 50 recurrent genital infections. Sixty-four isolates from 18 patients followed up for six months were subtyped by using a larger panel of monoclonal antibodies and predominant HSV1 and HSV2 subtypes were demonstrated. In addition to confirming recurrences, four possible reinfections were identified. Type-specific differences in the location of viral antigens in infected cells were noted and a possible association of this finding with the type-specific differences in rates of recurrence of genital infections discussed.
Herpes simplex virus-1 (HSV-1) infection of cultured human neural cells causes the accumulation of a host cell-encoded nuclear protein identified as a 57,000 mol.wt. stress protein by monoclonal antibody TI56. This protein is cell cycle-related in fibroblast, may mediate host cell control during HSV infection and could play a role in the regulation of HSV latency.
Three herpes simplex virus type I (HSV-I) glycoproteins of apparent molecular masses 103, 63, and 115 kD have been purified using virus-specific monoclonal antibodies (mAb) G8D1, C2D2, and T157, respectively. Both G8D1 and C2D2 neutralize HSV-I in vitro and passively protect CBA mice against HSV-I infection in vivo, whereas T157 is neither neutralizing nor passively protective. However, mice given a single subcutaneous injection of 30 micrograms 115 kD glycoprotein in saline were completely protected against lethal challenges of HSV-I administered intraperitoneally or in the footpad 7 d after immunization. In contrast, mice similarly immunized with 103 or 63 kD glycoproteins were only partially protected. The prophylactic immunity was correlated with an early induction of specific antibody, which became even more evident 3 d after virus challenge. There was a remarkable similarity in antibody isotype distribution between the responses to 115 kD glycoprotein and to heat-inactivated intact HSV-I. However, the prechallenge sera from 115 kD glycoprotein hyperimmunized mice were again neither virus-neutralizing nor passively protective. All three glycoproteins induced only low levels of delayed-type hypersensitivity (DTH). Pretreatment of mice with cyclophosphamide significantly enhanced DTH to 115 kD and 103 kD glycoproteins in the absence of antibody, but failed to confer significant immunity, indicating that DTH alone is insufficient for protection. Splenic and lymph node Ig- (B cell-depleted) cells from mice protectively immunized with 115 kD glycoprotein could adoptively transfer effective protection and enhance a virus neutralizing antibody response in normal recipients challenged with a lethal dose of HSV-I. Both the protection and the ability to enhance neutralizing antibody were diminished when the cells were treated with mAb GK 1.5 and complement. These results therefore demonstrate that the 115 kD glycoprotein, though not apparently containing accessible epitopes for the induction of virus-neutralizing antibody, possesses determinants capable of activating helper T cells. These L3T4+ cells confer strong protective immunity by enhancing protective antibody upon challenge infection, probably through associative help.
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