Biomedical subjects
C Wood
Publications and source records attributed to C Wood.
HIV promoter activity in primary antigen-specific human T lymphocytes.
Human retroviruses, such as the HIV, infects human T cells, and efficient HIV replication occurs primarily in activated T cells rather than resting cells. Increased HIV production is likely caused by the activation of the retroviral promoter, and the HIV promoter may be regulated by intracellular signals induced during immune stimulation. To examine the regulation of retroviral promoter activity in normal, Ag-specific primary T lymphoblasts, a heterogeneous population of primary human T cells was transfected with either the HIV promoter or a promoter from a different retrovirus, Rous sarcoma virus (RSV) by protoplast fusion technique. Transfected T cells responded normally to Ag or mitogen stimulation, and activation of these T cells increased both the HIV and RSV promoter activity. Promoter activity was assessed by using transient expression assays after the T cells were restimulated with Ag, mitogen, or IL-2. In situ hybridization of transfected human T cells showed that 68 to 95% of activated lymphocytes expressed CAT mRNA directed by HIV or RSV. Thus, protoplast transfection of primary T cells was efficient in that the majority of cells expressed CAT message. By deletion of different regions of the HIV promoter, the enhancer region was identified as necessary for effective HIV promoter activity. In addition these deletion studies identified a region that negatively affects HIV promoter activity in primary T cells. Cotransfection of the HIV promoter with the HIV transactivator protein, tat, increases HIV promoter activity in both resting and activated primary human T cells only when the tat target sequences were present.
A controlled study of luteinizing hormone-releasing hormone agonist (buserelin) for the induction of folliculogenesis before in vitro fertilization.
Treatment with clomiphene citrate and human menopausal gonadotropin (HMG) is often used to induce folliculogenesis before in vitro fertilization, but not all women have an adequate response. It has been hypothesized that abnormally high levels of luteinizing hormone (LH) may contribute to the reduced folliculogenesis. We therefore performed a controlled, open trial in which treatment with buserelin, an agonist of luteinizing hormone-releasing hormone citrate and HMG in 44 consecutive women in whom no oocytes or only one had been produced by standard treatment with clomiphene and HMG. Twenty-nine women received buserelin with HMG, and 15 received clomiphene citrate with HMG. The median number of oocytes per patient recovered from those who received buserelin with HMG was 4 (range, 0 to 19), as compared with 0 (range, 0 to 5) in those who received clomiphene citrate with HMG. The fertilization rates of oocytes recovered from both groups of patients were similar (75.8 percent and 76.5 percent, respectively). Fifty-four percent of patients given buserelin with HMG underwent triple-embryo transfer, as compared with 13 percent of those given clomiphene citrate with HMG. Pregnancy (n = 3) occurred only among the patients receiving buserelin with HMG. In the buserelin-HMG group, significantly fewer oocytes were recovered from patients with occult ovarian failure (infertility and elevated follicular-phase levels of follicle-stimulating hormone, with regular menses) (median, 1; range, 0 to 4) than from those with other causes of infertility (median, 8; range, 0 to 19). Our data suggest that, except in women with occult ovarian failure, buserelin and HMG improve embryologic and clinical outcomes in patients with previously unsatisfactory stimulation of the ovaries for in vitro fertilization.
Analysis of progress curves for enzyme-catalysed reactions. Automatic construction of computer programs for fitting integrated rate equations.
The computer analysis of progress curves for enzyme-catalysed reactions involves a series of mathematical and computational tasks. The three most daunting of these are the derivation of an integrated rate equation, solving this equation so that the amount of product formed by the reaction at any time can be calculated, and incorporating this solution into a non-linear-regression computer program. This paper describes the basis of a computer program that greatly simplifies the problem. The proposed mechanism is specified in the familiar kinetic constant form, which is automatically translated into a program capable of fitting this mechanism to a series of experimental progress curves. The approach is illustrated for a reversible reaction with one substrate and one product, and tested with some data obtained for the fumarase reaction. A copy of the program has been deposited as Supplementary Publication SUP 50148 (13 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1989) 257, 5.
Kinetics, quantitative analysis and radioimmunolocalization using indium-111-HMFG1 monoclonal antibody in patients with breast cancer.
HMFG1 tumour associated monoclonal antibody IgG1 and F(ab')2 fragments were radiolabelled with indium-111 and used to study patients with breast cancer. In vitro and in vivo stability of the radiolabelled antibodies was shown to be satisfactory. Thirty patients with primary breast cancer underwent tumour resection and quantitative evaluation of the radioactivity in the tumour and normal tissues following administration of specific and non-specific antibodies. The mean tumour uptake of HMFG1 F(ab')2 fragments at 24 h was significantly higher (P less than 0.05) than the intact IgG but at 48 h there was no difference. The mean tumour uptake with the specific antibody was higher than the non-specific antibody of the same subclass (P less than 0.05). Lymph node metastases showed higher antibody uptake than the corresponding primary tumours (P less than 0.05). Fifteen patients with primary or metastatic breast cancer were investigated by external body scintigraphy using HMFG1 F(ab')2 fragments. Successful localisation was observed in approximately 50% of the primary and metastatic lesions with no false positive results. All the patients had observable concentration of 111In in the liver (20% of the injected dose), the kidneys and the spleen. Following i.v. administration, F(ab')2 fragments cleared from the blood more rapidly than the intact IgG. We conclude that HMFG1 F(ab')2 fragments can localise specifically and faster than intact IgG in breast cancer but the sensitivity of the radioimmunoscintigraphy is relatively low. This method needs further improvement before becoming clinically useful for detecting and staging breast cancer.
In vitro fertilization, a practical option after failed artificial insemination with donor semen.
The progress of 80 couples who failed to conceive by donor insemination was followed through in vitro fertilization cycles using donor sperm. The outcome was better than that for couples undergoing IVF for tubal disease and significantly better than their chance with further cycles of donor insemination.
Human immunodeficiency viral long terminal repeat is functional and can be trans-activated in Escherichia coli.
The long terminal repeat (LTR) of the human immunodeficiency virus (HIV) contains the viral promoter, which is responsible for viral gene expression in eukaryotic cells. We have demonstrated that HIV LTR can also function as a promoter in Escherichia coli. A recombinant plasmid containing the HIV LTR linked to the chloramphenicol acetyltransferase gene can express the enzyme efficiently upon transformation into bacteria. Mung bean nuclease analysis mapped the bacterial transcriptional start site of the promoter to the U3 region of the LTR, in contrast to transcription in eukaryotic cells, which initiates in the U3-R boundary of the LTR. The HIV LTR, besides being fully functional in E. coli, can also be specifically trans-activated by the HIV tat gene product. Trans-activation is demonstrated by an increase in chloramphenicol acetyltransferase activity as well as an increase in the mRNA level of the enzyme. This trans-activation of HIV LTR by tat protein in bacteria offers a useful system to investigate further the specific interaction between tat protein with HIV LTR and the mechanisms of trans-activation.
Possibility of HIV gp41 and thymosin beta-4 sharing the same antigenic epitope.
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Transactivation of human immunodeficiency virus promoter by human herpesvirus 6.
Patients with acquired immunodeficiency syndrome (AIDS) are often infected with a number of other heterologous viruses in addition to the initial human immunodeficiency virus (HIV) infection, and these agents could act as potential reactivating agents of latent HIV. A new antigenically distinct herpesvirus, designated human herpesvirus 6 (HHV-6), has recently been isolated from patients with AIDS and has been shown to infect a number of different human cells, specifically human T cells, B cells, and glial cells. Since these are some of the same cells that harbor the AIDS virus, it is quite important to determine any interaction between this new herpesvirus and HIV. In this report, we demonstrate that HHV-6 can trans-activate the HIV promoter in human T-cell lines as measured by the expression of the bacterial gene chloramphenicol acetyltransferase. This indicates that stimulation of HIV gene expression by HHV-6 could play a role in HIV pathogenesis.
Use of TrpE/Gag fusion proteins to characterize immunoreactive domains on the human immunodeficiency virus type 1 core protein.
The human immunodeficiency virus (HIV) p24 core protein is one of the most immunogenic of HIV structural proteins. Infected individuals develop high titers of antibodies against p24 early in infection, which makes anti-p24 antibodies important serological markers. However, despite the clinical importance of the anti-p24 response, no systematic study to characterize the antigenic domains on the p24 protein has been reported. We report here on the use of 12 overlapping fragments of the HIV type 1 p24 protein, synthesized in bacteria as TrpE/Gag fusion proteins, to identify at least two and possibly three antigenic domains on the p24 protein. In addition, we note that different HIV-seropositive sera exhibited different patterns of reactivity with the p24 domains presented on our fusion proteins.
Seizures presenting as apnoea.
Between the ages of 3 and 6 months a baby boy presented with repeated, non-specific episodes of cyanosis, apnoea, bradycardia, and abnormal movements of the limbs. The episodes were severe and required resuscitation and several admissions to hospital. Initial investigations showed only signs of oesophagitis. Despite treatment of the oesophagitis the symptoms recurred, and electroencephalography and polygraphy eventually showed evidence of minor seizures. Severe epilepsy with tonic-clonic seizures developed when he was 6 months old.
Metastatic malignant melanoma arising from a common blue nevus in a patient with subacute cutaneous lupus erythematosus.
We describe a 66-year-old black male who first presented with subacute cutaneous lupus erythematosus (SCLE) and was later found to have malignant melanoma adjacent to a common blue nevus. The melanoma was located on the left buttock and in several left inguinal lymph nodes. Following complete resection and lymph node dissection the patient developed widespread leukoderma. To our knowledge this is the first report of malignant melanoma arising in a common blue nevus. The literature on SCLE and leukoderma in the setting of melanoma is reviewed.
Cytomegalovirus infection in pediatric liver recipients. A virological survey and prophylaxis with CMV immune globulin and early DHPG treatment.
From November 1985 to August 1987, 22 children underwent orthotopic liver transplantation (OLT). Primary cytomegalovirus (CMV) infection was observed in 3 of 10 seronegative recipients (30%). It was severe in 2 cases, which were treated successfully by a combination of DHPG and CMV hyperimmune globulin. From September 1987 to August 1988, a virologic survey was undertaken. It enabled us to take prophylactic measures and to make an early diagnosis of CMV infection, permitting early antiviral treatment. During this period, 26 children received liver grafts. Nine of 13 seronegative recipients (69, 2%) developed primary CMV infection. Seven had received immunoprophylaxis and 8 were treated by DHPG. None had severe disease and all improved rapidly.
Cyclosporine nephrotoxicity and dermal vascular alterations in renal transplants.
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Morbidity, mortality, and quality of life in long-term survivors of an integrated dialysis/renal transplant programme.
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[Portal system obstruction of delayed onset following neonatal Staphylococcus aureus infection].
Two neonates underwent staphylococcal septicemia with multiple intrahepatic abscesses, following umbilical catheterization in one case and due to superinfected heel puncture in the other case. At the first examination, liver ultrasonography showed multiple hypoechogenic areas and assessed patency of the portal vein flow. In spite of clinical, biological and sonographic recovery within the following weeks, portal hypertension due to seemingly late portal vein thrombosis occurred. These clinical reports indicate the need for a protracted echosonographic supervision of neonatal intrahepatic abscesses and portal vein patency before asserting complete recovery.
Fatal Fusarium solani infections in baby sharks.
The occurrence of fatal fusariosis in baby bonnethead sharks (Sphyrna tiburo) born at the National Aquarium, Baltimore, Maryland, is reported. An atypical strain of Fusarium solani was cultured from the tissues of two of the infected sharks following postmortem examination. Histopathology revealed an apparent predilection of the fungus for hyaline cartilage. Invasion of the cartilage resulted in hyphae with a distorted morphology. In slide culture the fungus displayed the unusual characteristic of terminal chlamydoconidium generation on macroconidia; this may be of some taxonomic significance.
Characterization of immunoreactive epitopes of the HIV-1 p41 envelope protein using fusion proteins synthesized in Escherichia coli.
We have identified several immunoreactive epitopes on the human immunodeficiency virus (HIV) type 1 transmembrane envelope protein by synthesizing various regions of the protein as fusions to the trpE gene in Escherichia coli. Ten fusion clones which expressed overlapping peptides were found to contain epitopes reactive with antibodies in sera of North American (NAm) and West African (WAf) patients with acquired immune deficiency syndrome (AIDS). An immunodominant epitope which reacted with all HIV-infected patients' sera was mapped to a 51-amino acid sequence in the N terminus of p41. A novel epitope was also identified in the C terminus of p41 which was reactive with 41% and 48% of the sera tested from NAm and WAf, respectively. In addition, several minor epitopes were identified. We observed that sera from WAf reacted more strongly to minor HIV-1 p41 epitopes than did sera from similarly infected individuals in NAm. We also report on the detection of antibodies from patients with HIV-2 infection in WAf which cross react with HIV-1 p41 recombinant envelope antigens.