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Biomedical subjects

R Lau

Publications and source records attributed to R Lau.

At least 55 records · Page 3Linked to original sources
PubMed1995

AIDS in Africans living in London.

OBJECTIVES: To investigate the presentation of HIV infection and AIDS amongst Africans diagnosed with AIDS living in London. METHODS: Identification of all AIDS cases of African origin attending four HIV specialist centres in South London--Guy's, King's, St George's and St Thomas' Hospitals--up to March 1994, by retrospective review of case notes of all HIV positive patients. RESULTS: Of 86 patients (53 women, 33 men) studied, 59 (69%) were from Uganda. The most frequent AIDS-defining diagnoses were: Pneumocystis carinii pneumonia (PCP) 21%, tuberculosis (TB) 20% (extrapulmonary TB 14%, pulmonary TB 6%), cerebral toxoplasmosis 14%, oesophageal candida 13%, cryptococcal meningitis 11%, wasting 6%, herpes simplex infection > 1 month 5%, Kaposi's sarcoma 5%, other 6%. Cytomegalovirus retinitis was diagnosed in one case. Late presentation was common; 70% were diagnosed HIV positive when admitted to hospital. The diagnosis of AIDS was coincident with a first positive HIV test result in 61%. The mean CD4 counts at both HIV and AIDS diagnoses were similar in both men and women: 87 x 10(6)/l and 74 x 10(6)/l in men and 99 x 10(6)/l and 93 x 10(6)/l in women respectively. Overall, TB 21 (24%) (extrapulmonary TB 12, pulmonary TB 9) was either the AIDS-defining diagnosis or was detected within three months of this event. Sixty-two per cent of TB cases were diagnosed within twelve months of entry to the UK compared to 34% of all other AIDS cases. The prevalence of STD was very low; genital herpes was the commonest STD: 17% of the women, 9% men; 28% of the men and 11% of the women tested had a positive TPHA test. In cases known to be HIV-positive prior to an AIDS diagnosis, 41% took prophylaxis for PCP and 45% had taken zidovudine (ZDV). Forty two of the study participants had 89 children: 59 of these children had mothers in the study. Overall, 37 (42%) of the children had lost at least one parent at the time of data assessment. CONCLUSIONS: PCP and TB were the most common initial AIDS-defining diagnoses. The majority of TB cases were diagnosed within 12 months of entry to the UK. An AIDS-defining diagnosis was the first manifestation of HIV-related illness in the majority of patients. Because of late presentation to medical services, access to treatments for HIV infection and prophylaxis against opportunistic infections was limited. Extending the role of clinics and staff into the community might facilitate both earlier presentation and access to services. Future provision of local services will need to be sensitive to the requirements of individuals from different cultures and backgrounds.

Acquired Immunodeficiency Syndrome↗
PubMed1995

B-lineage lymphoid blast crisis in juvenile chronic myelogenous leukemia: II. Interleukin-1-mediated autocrine growth regulation of the lymphoblasts.

A pre-B acute lymphoblastic leukemia (ALL) cell line with monosomy 7 was established from a child with juvenile chronic myelogenous leukemia (JCML) in lymphoid blast crisis. Analysis of the growth properties of the cell line, termed 'W1' showed an interleukin-1 (IL-1) mediated autocrine pattern of cell proliferation with the following features: W1 colony growth without added growth factor was density-dependent and colony growth was augmented with serum-free autologous cell culture supernatant; exogenous IL-1 beta had a growth-promoting effect on W1 colony numbers when cells were seeded at low density; W1 cells constitutively expressed mRNA for IL-1 beta, and high levels of IL-1 beta were measured in W1 cell lysates; anti-IL-1 beta antibodies as well as IL-1 receptor antagonist markedly suppressed W1 colony growth when either was added to cultures of cells seeded without growth factors at low density; anti-GM-CSF antibodies and anti-IL-3 antibodies had no inhibitory effect on W1 colony growth. Whereas W1 colony growth was also augmented by adding IL-3, IL-4, IL-6, IL-7, GM-CSF, Steel factor and erythropoietin individually to the cultures, W1 cells did not constitutively express mRNA for any of these cytokines. W1 colony growth was markedly suppressed by exogenous TNF-alpha which contrasts sharply with the autocrine growth promoting effect of TNF-alpha on myelomonocytic elements of JCML in 'chronic' phase. The inhibitory effect of TNF-alpha on W1 cells was not due to downregulation of IL-1 production. The IL-1-dependent growth of W1 cells appeared to be unique because none of five other pre-B lineage ALL cell lines established as controls showed an autocrine growth loop via IL-1. W1 cells provide a valuable opportunity to examine the relationship of monosomy 7, B-lineage acute lymphoblastic leukemia, aberrant genetic expression of cytokines and their receptors, and IL-1 mediated autocrine cell growth in cancer.

B-Lymphocytes↗
PubMed1993

Epstein-Barr virus gene expression in oral hairy leukoplakia.

A combination of Northern blotting and sequencing of clones from a cDNA library constructed using RNA isolated from oral hairy leukoplakia (OHL) has been used to study Epstein-Barr virus (EBV) gene expression in this AIDS-associated lesion, the only accessible source of in vivo-replicating EBV. Because of the limited amount of RNA available, Northern blotting was only useful for detection of very abundant EBV transcripts in the OHL biopsies. Analysis of cDNA clones containing the BdRF1, BCRF1, gp350/220, BARF0, and BKRF4 reading frames and further characterization of RNA structures spanning BCRF1 (viral IL-10) in lymphocytes infected with EBV has provided a preliminary comparison of some virus replicative gene expression in its two main host cell types. No expression of EBNA-1, EBNA-2, or EBNA-3A RNA was detected in the oral hairy leukoplakia cDNA library.

Animals↗
PubMed1993

Differential effect of HTLV infection and HTLV Tax on interleukin 3 expression.

To characterize the interactions between human T-cell leukemia virus (HTLV) infection and cellular gene expression, we examined the expression of the lymphokine interleukin 3 (IL-3) in the presence and absence of HTLV infection. IL-3, like granulocyte-macrophage colony-stimulating factor (GM-CSF), is produced by activated but not resting T cells, but although GM-CSF is constitutively expressed in HTLV-infected T cells IL-3 mRNA cannot be detected in either unstimulated or mitogen-stimulated HTLV-infected cells by polymerase chain reaction (PCR) analysis. In contrast, transient co-transfection studies with an IL-3 promoter-CAT reporter gene and an HTLV-II Tax expression construct demonstrate that Tax can transactivate the IL-3 promoter in HTLV-uninfected T cells. To determine whether differences in IL-3 promoter-binding proteins present in HTLV-infected and uninfected T cells account for this discrepancy, DNAase I footprinting of the IL-3 promoter was performed. Although crude nuclear extracts from both cell types protected the IL-3 sequences located between base pairs -168 and -125, the sequences between -125 and -103, which contain the lymphokine consensus sequences CK-1 and CK-2, were protected by extracts from HTLV-infected but not HTLV-uninfected T cells. Deletion of the region containing the CK-1 and CK-2 sequences from an IL-3 promoter CAT construct resulted in a sixfold rise in promoter activity in HTLV-infected but not uninfected T-cell lines, indicating that this region participates in the repression of IL-3 gene expression in HTLV-infected T cells.

Base Sequence↗
PubMed1992

Differential splicing of Epstein-Barr virus immediate-early RNA.

A variant form of splicing of RNA crossing the Epstein-Barr virus (EBV) BZLF1 gene was observed in the late productive cycle of EBV. This splice omits the middle exon of BZLF1 and joins the outer two exons of BZLF1 in frame, but the shortened form of BZLF1 protein (Z delta) could not be detected in natural EBV infections.

Blotting, Western↗
PubMed1992

Characterization and assessment of an avian repetitive DNA sequence as an icterid phylogenetic marker.

The first tandemly repeated sequence examined in a passerine bird, a 431-bp PstI fragment named pMAT1, has been cloned from the genome of the brown-headed cowbird (Molothrus ater). The sequence represents about 5-10% of the genome (about 4 x 10(5) copies) and yields prominent ethidium bromide stained bands when genomic DNA cut with a variety of restriction enzymes is electrophoresed in agarose gels. A particularly striking ladder of fragments is apparent when the DNA is cut with HinfI, indicative of a tandem arrangement of the monomer. The cloned PstI monomer has been sequenced, revealing no internal repeated structure. There are sequences that hybridize with pMAT1 found in related nine-primaried oscines but not in more distantly related oscines, suboscines, or nonpasserine species. Little sequence similarity to tandemly repeated PstI cut sequences from the merlin (Falco columbarius), saurus crane (Grus antigone), or Puerto Rican parrot (Amazona vittata) or to HinfI digested sequence from the Toulouse goose (Anser anser) was detected. The isolated sequence was used as a probe to examine DNA samples of eight members of the tribe Icterini. This examination revealed phylogenetically informative characters. The repeat contains cutting sites from a number of restriction enzymes, which, if sufficiently polymorphic, would provide new phylogenetic characters. Sequences like these, conserved within a species, but variable between closely related species, may be very useful for phylogenetic studies of closely related taxa.

Animals↗
PubMed1991

Epstein-Barr virus infection in oral hairy leukoplakia: virus replication in the absence of a detectable latent phase.

Epstein-Barr virus (EBV) infects both B lymphocytes and oropharyngeal epithelium, and it has been argued that the true reservoir of virus persistence in vivo is the self-renewing basal epithelial compartment. The identification of oral hairy leukoplakia (HL) of AIDS patients as a clinically apparent focus of EBV replication in lingual epithelium therefore provides a means of studying the EBV-epithelial cell interaction in situ. Replicative EBV DNA and productive cycle antigens are restricted to the upper, more differentiated epithelial layers in HL, and here we have applied highly sensitive in situ hybridization and immunohistological methods to examine the lower basal/suprabasal layers for evidence of latent EBV infection. We could not detect EBV DNA in these layers using an in situ DNA hybridization protocol which, on reference B cell lines, detected 1 viral genome/cell. Likewise, using sensitive in situ RNA hybridization for both the small non-polyadenylated EBER RNAs (abundant transcripts seen in all known forms of EBV latency) and the latent membrane protein (LMP) mRNA (the most abundant viral mRNA in B lymphoblastoid cell lines), the basal/suprabasal cells in HL were consistently negative; immunohistological staining with specific monoclonal antibodies also gave no evidence of latently infected LMP-positive cells. When the biopsy extracts were analysed by immunoblotting with selected human antisera, in addition to abundant productive cycle antigens, a band of constant size (66K) was observed which also reacted with immunopurified antibodies monospecific for one of the latency-associated nuclear antigens, EBNA 1; the cellular origin of this EBNA 1 could not be ascertained, but it is possible that in HL the protein is expressed during the productive cycle. The absence of demonstrable EBV latency in the basal/suprabasal cells of HL suggests that this is purely a virus replicative lesion which is sustained by continual re-infection of the maturing epithelium, not by the maturation of latently infected cells from the basal compartment.

Antigens, Viral↗
PubMed1991

Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia.

The BZLF1 protein of Epstein-Barr virus (EBV) is a key immediate-early protein which has been shown to disrupt virus latency in EBV-infected B cells. We have generated a monoclonal antibody, BZ1, to BZLF1 which reacts in immunohistology, immunoblotting, and immunoprecipitation and which recognizes both the active, dimeric form and the inactive, monomeric form of the protein. Biopsies of oral hairy leukoplakia, an AIDS-associated lesion characterized by high-level EBV replication, were examined by immunohistochemistry using the BZ1 monoclonal antibody. A differentiation-associated pattern of BZLF1 expression was observed, BZ1 reacting with nuclei of the upper spinous layer of the lesion. This finding suggests that the BZLF1 promoter may be regulated by the degree of squamous differentiation. A comparison of in situ hybridization to EBV DNA and viral capsid antigen staining with BZ1 reactivity suggested that BZLF1 expression precedes rampant virus replication. The inability to detect EBV in the lower epithelial layers of oral hairy leukoplakia raises questions concerning the nature of EBV latency and persistence in stratified squamous epithelium.

Antibodies, Monoclonal↗
PubMed1990

Episcleral radioactive plaque therapy: initial clinical experience with 56 patients.

Between 1983 and 1987, 56 patients with choroidal melanoma were treated at the University of Southern California with episcleral plaque (RPT). There were 29 female and 27 male patients, with a mean age of 59 years. Tumor stage at diagnosis was T2 in 18 (32%) and T3 in 38 (68%) patients. The tumor height ranged from 2.9 to 15 mm (mean 6.8 mm). Radial dimensions ranged from 5 to 25 mm (mean 13.2 mm), and circumference ranged from 7 to 23 mm (mean 12.3 mm). Most (77%) patients had posteriorly located tumors, including 18% that were juxtapapillary. Custom-designed gold plaques were utilized in this study. Radioactive isotopes used were 125I for 26 procedures or 192Ir for 31 procedures. A total of 56 patients were treated, with one patient having two procedures. Radiation doses at the tumor apex ranged from 29.8 to 165.4 Gy (mean 94.5 Gy), with the dose at 5-mm depth ranging from 70.5 to 430 Gy (mean 161.5 Gy). Follow-up ranged from 29 to 57 months (mean 39 months). The overall 4-year survival was 96%, with a 91% incidence of free-of-disease progression at 4 years. The majority (84%) of patients experienced a decrease in tumor height, with 27 (48%) patients having greater than 50% decrease. Increase in tumor height was noted in 5 (9%) and no change in 4 (7%) patients. Useful vision (greater than 5/200) was observed in 59% of patients, including 21% who had improved vision. Metastatic tumor occurred in 5 (9%) patients, with a mean time to metastases of 14 months. There was a good correlation between radial tumor dimension and metastatic disease, p less than 0.001. Treatment complications were observed in 34 (61%) patients, with cataract and retinopathy being the most common. Enucleation was performed in 11 (20%) patients, with a mean time to enucleation of 14.5 months. Causative factors for enucleation were treatment complications in 6 and tumor progression in 5 patients. Enucleations were required primarily in patients with tumors greater than 8 mm in height (p = 0.009). Improved RPT techniques with three-dimensional dosimetry are needed to reduce the overall incidence of treatment complications. Adjuvant hyperthermia is being investigated in an attempt to improve tumor control in patients with larger tumors.

Adult↗
PubMed1990

Dendritic cell infection, depletion and dysfunction in HIV-infected individuals.

Immune responses in resting T cells are initiated by the presentation of antigen by bone marrow-derived dendritic cells (DC). Normal DC are susceptible to infection with human immunodeficiency virus (HIV) in vitro (Patterson & Knight, 1987) and this blocks their capacity to stimulate T-cell responses to other antigens (Macatonia, Patterson & Knight, 1989a). To study the relationship between HIV and DC in patients and its relevance to the pathogenesis of disease, DC have been isolated from the blood of individuals in the different clinical categories, counted, examined for the presence of virus genome and their antigen-presenting capacity measured. Infection, depletion and impaired function of DC occur in early HIV infection. HIV seropositive patients who were asymptomatic and those with symptoms of disease had significantly reduced numbers of DC, but patients with persistent generalized lymphadenopathy had normal numbers. Between 3% and 21% of DC, identified as large low-density cells not bearing monocyte, lymphocyte or natural killer cell markers, were infected with HIV, as indicated by in situ hybridization. Less than 0.12% of the lymphocytes or monocytes were infected. The DC from infected individuals were poor at enhancing responses to the mitogen concanavalin A (Con A). They also caused low levels of stimulation in allogeneic lymphocytes in mixed leucocyte cultures. By contrast, T cells from asymptomatic patients gave normal T-cell responses to uninfected allogeneic DC, although those from acquired immunodeficiency syndrome (AIDS) patients did show reduced responsiveness. Defects in DC thus precede both the appearance of symptoms and changes in T cells and may be instrumental in the development of AIDS. Furthermore, since DC numbers and function differ at different stages of disease, monitoring these may contribute to clinical assessment and lead to new therapeutic approaches.

Cell Count↗
PubMed1987

Influence of thyroidal status on pituitary content of thyrotropin beta- and alpha-subunit, growth hormone, and prolactin messenger ribonucleic acids.

Thyroidectomized rats were used to study the effects of a single injection of T3 on pituitary mRNA synthesis and hormone secretion. T3 was injected ip at doses of 0, 0.2, 1, or 5 micrograms/100 g body weight, and and animals were killed 24 h later. T3 caused a significant decrease in serum TSH, but caused no significant change in either serum GH or PRL. Pituitary mRNA was quantified by slot blot hybridization with cDNA probes specific for alpha-TSH, beta-TSH, PRL, and GH. We found that both the alpha and beta mRNA subunits decreased, that PRL mRNA remained relatively unchanged, and that GH mRNA increased with increasing T3 dose. The data show that a single dose of T3 can profoundly influence mRNA levels in the anterior pituitary; the lowest dose of T3 caused maximum inhibition of alpha-TSH mRNA while beta-TSH mRNA declined further in a dose-dependent manner.

Animals↗
PubMed1986

Differential expression of thyrotropin hormone genes by GH3 cells and the normal rat pituitary.

RNAs from GH3 cells, a rat clonal cell line, and anterior pituitaries of normal rats have been isolated and assayed for the presence of transcripts coding for the alpha- and beta-subunits of thyrotropin hormone (TSH) by hybridization to their respective cDNAs. Northern analysis indicated that GH3 cells lack both TSH transcripts, and that normal anterior pituitary cells contain mRNA for both the alpha- and beta-subunits approximating 800 and 700 nucleotides, respectively. An examination of the DNAs from GH3 cells and normal anterior pituitary tissue revealed no organizational difference when the restriction digests were subjected to Southern analysis. The lack of TSH secretion by GH3 cells is probably not due to sequence modification of genomic DNA, but to undetermined factors controlling transcription.

Animals↗
PubMed1984

Thyroid T4 5'-deiodinase activity in normal and abnormal human thyroid glands.

To investigate the activity of the thyroid gland to convert T4 to T3, we measured the activity of thyroid T4 5'-deiodinase in the following human thyroid glands: 9 normal glands, 5 Hashimoto's thyroiditis, 13 follicular adenomas, 11 methimazole (MMI)-treated Graves' disease (GD), 11 propranolol iodide-treated GD, and 8 propylthiouracil (PTU)-treated GD. The enzyme activity was determined by the ability of 100,000 X g pellet of the thyroid homogenate to convert T4 to T3 in vitro. Normal thyroids showed the enzyme activity of 1.59 +/- 0.18 (mean +/- SEM) pmol T3/mg protein/min. Euthyroid Hashimoto's thyroiditis displayed the enzyme activity of 1.01 +/- 0.15 pmol T3/mg protein/min, which was similar to the normal thyroid enzyme activity. The hypothyroid gland of Hashimoto's thyroiditis showed the enzyme activity of 1.8 pmol T3/mg protein/min. Follicular adenomas showed a wide range of enzyme activity with the mean level of 3.24 +/- 0.82 pmol T3/mg protein/min that did not differ significantly from that of the normal thyroids. Interestingly, one adenoma, despite TSH suppression that ordinarily decreases enzyme activity, showed the greatest activity of 11.0 pmol T3/mg protein/min. Graves' thyroids following treatment with MMI, PTU, and propranolol-iodide showed enzyme activities of 4.61 +/- 0.53, 3.95 +/- 0.43, and 3.51 +/- 0.46 pmol T3/mg protein/min, respectively; all these values were greater than that of the normal thyroids (P less than 0.01), but did not differ significantly when compared with each other. In summary, thyroid glands with Hashimoto's thyroiditis had activities of T4 to T3 conversion similar to the normal thyroid glands.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1980

Channeling health: a review of the evaluation of televised health campaigns.

This article reviews efforts to assess the effectiveness of television programs on changing health behaviors. The relatively limited literature to date has featured primarily correlational studies which permitted no causal conclusions. The few experimental studies available present a mixed picture. Numerous methodologic problems beset any effort at assessment of effectiveness. Perhaps the greatest difficulty is operationalizing a design that permits true experimental manipulation on a relevant sample without contamination. The several methodologic problems and some potential means of surmounting them are discussed.

Attitude to Health↗