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J Lamb

Publications and source records attributed to J Lamb.

At least 73 records · Page 4Linked to original sources
PubMed1991

Comparative pathology of breast cancer in a randomised trial of screening.

In the Edinburgh Randomised Breast Screening Project (EBSP) to December 1988 there were 500 cancers in the study population invited to screening and 340 cancers identified in the control population. The size and negative lymph node status characteristics of invasive cancers from the two populations were significantly different (P less than 0.05). The cancers detected by screening were predominantly 'early stage', with 16% noninvasive (PTIS) and 42% invasive stage I (pT1 node negative), whereas cancers were frequently 'late stage' (more than pT2) and inoperable in nonattenders (44%) and controls (36%). Grouped according to customary size ranges of invasive cancers, the proportion of cases lymph node positive differed in those screen detected compared with controls, but the benefit in favour of screen detection was not constant. In comparisons of cancers detected at prevalence and incidence screens, as a test of conformity with screening theory, no significant differences were apparent according to size and lymph node status, yet the characteristics of histological type of cancer discriminated significantly (P less than 0.05). When these same histological characteristics were used to compare survival, the capacity to separate invasive cancers into two groups having good and poor survival probabilities was evident, with a significant improvement for the screen detected poor survival group compared with controls (P less than 0.05).

Breast Neoplasms↗
PubMed1991

Stress-induced modulation of antigen-presenting cell function.

The effect of two means of inducing a stress response, heat and oxygen radicals, on the ability of an HLA-DR1 B-cell line to stimulate DR1-restricted and anti-DR1 auto- and alloreactive T-cell clones has been examined. Both forms of stress enhanced the ability of B cells to stimulate auto- and alloreactive T-cell clones and to present peptide to an influenza-virus specific T-cell clone. Furthermore, the ability of the B-cell line to present whole influenza virus was augmented by heat stress. The stress-induced enhancement of T-cell responses coincided with a modest increase in the cell-surface expression of major histocompatibility class II products. This was, however, insufficient to account for the observed functional effects. In contrast to these effects, presentation of whole antigen was inhibited by the oxygen radical intermediate, hydrogen peroxide (peroxide), in a dose-dependent manner. When analysed by SDS-PAGE, it was found that whilst overall protein synthesis decreased following both types of stress, increased synthesis of heat-shock proteins (HSP), and in particular the 70,000 MW HSP, was only evident following heat stress. The absence of an increase in the synthesis of HSP 70, in the antigen-presenting cells (APC) following the uptake of UV-treated influenza virus, however, implied that HSP 70 induction was not necessary for the presentation of whole antigen. The effects of peroxide stress appeared to be qualitatively different in several respects. First, peroxide treatment did not cause the induction of any stress proteins; second, peroxide abolished the presentation of whole antigen. In addition, heat stress of APC was unable to protect from the adverse effects of peroxide treatment, in that cells treated sequentially with heat, followed by peroxide, were unable to present whole influenza virus. In order to determine the stage of antigen presentation at which peroxide was causing inhibition, APC were treated at varying time-points after pulsing with antigen. The kinetics of the peroxide effect paralleled those of aldehyde fixation. Taking these results together it would appear that peroxide interferes with some aspects of the antigen-processing pathway.

Antigen-Presenting Cells↗
PubMed1990

Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation, characterization and regulation of the SPO7 sporulation gene.

SPO7 is one of several previously identified genes from the yeast Saccharomyces cerevisiae that is required for sporulation but not for vegetative growth. The SPO7 gene has been cloned by functional complementation and physically mapped 15-16 kb to the left of CEN1. Gene-disruption experiments confirmed that the cloned gene was the bona fide SPO7 gene. SPO7 codes for a 0.95-kb transcript that is expressed at approximately the same level in both vegetative and sporulating cells. The gene was sequenced and has the capacity to encode a 259-amino acid protein that does not appear to be related to other known proteins.

Amino Acid Sequence↗
PubMed1990

Effect of ATP on actin filament stiffness.

Actin is an adenine nucleotide-binding protein and an ATPase. The bound adenine nucleotide stabilizes the protein against denaturation and the ATPase activity, although not required for actin polymerization, affects the kinetics of this assembly Here we provide evidence for another effect of adenine nucleotides. We find that actin filaments made from ATP-containing monomers, the ATPase activity of which hydrolyses ATP to ADP following polymerization, are stiff rods, whereas filaments prepared from ADP-monomers are flexible. ATP exchanges with ADP in such filaments and stiffens them. Because both kinds of actin filaments contain mainly ADP, we suggest the alignment of actin monomers in filaments that have bound and hydrolysed ATP traps them conformationally and stores elastic energy. This energy would be available for release by actin-binding proteins that transduce force or sever actin filaments. These data support earlier proposals that actin is not merely a passive cable, but has an active mechanochemical role in cell function.

Actins↗
PubMed1990

A truncated human chromosome 16 associated with alpha thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n.

The instability of chromosomes with breaks induced by X-irradiation led to the proposal that the natural ends of chromosomes are capped by a specialized structure, the telomere. Telomeres prevent end-to-end fusions and exonucleolytic degradation, enable the end of the linear DNA molecule to replicate, and function in cell division. Human telomeric DNA comprises approximately 2-20 kilobases (kb) of the tandemly repeated sequence (TTAGGG)n oriented 5'----3' in towards the end of the chromosome, interspersed with variant repeats in the proximal region. Immediately subtelomeric lie families of unrelated repeat motifs (telomere-associated sequences) whose function, if any, is unknown. In lower eukaryotes the formation and maintenance of telomeres may be mediated enzymatically (by telomerase) or by recombination; in man the mechanisms are poorly understood, although telomerase has been identified in HeLa cells. Here we describe an alpha thalassaemia mutation associated with terminal truncation of the short arm of chromosome 16 (within band 16p13-3) to a site 50 kb distal to the alpha globin genes, and show that (TTAGGG)n has been added directly to the site of the break. The mutation is stably inherited, proving that telomeric DNA alone is sufficient to stabilize the broken chromosome end. This mechanism may occur in any genetic disease associated with chromosome truncation.

Base Sequence↗
PubMed1990

Resemblance of actin-binding protein/actin gels to covalently crosslinked networks.

The maintainance of the shape of cells is often due to their surface elasticity, which arises mainly from an actin-rich cytoplasmic cortex. On locomotion, phagocytosis or fission, however, these cells become partially fluid-like. The finding of proteins that can bind to actin and control the assembly of, or crosslink, actin filaments, and of intracellular messages that regulate the activities of some of these actin-binding proteins, indicates that such 'gel-sol' transformations result from the rearrangement of cortical actin-rich networks. Alternatively, on the basis of a study of the mechanical properties of mixtures of actin filaments and an Acanthamoeba actin-binding protein, alpha-actinin, it has been proposed that these transformations can be accounted for by rapid exchange of crosslinks between actin filaments: the cortical network would be solid when the deformation rate is greater than the rate of crosslink exchange, but would deform or 'creep' when deformation is slow enough to permit crosslinker molecules to rearrange. Here we report, however, that mixtures of actin filaments and actin-binding protein (ABP), an actin crosslinking protein of many higher eukaryotes, form gels rheologically equivalent to covalently crosslinked networks. These gels do not creep in response to applied stress on a time scale compatible with most cell-surface movements. These findings support a more complex and controlled mechanism underlying the dynamic mechanical properties of cortical cytoplasm, and can explain why cells do not collapse under the constant shear forces that often exist in tissues.

Actinin↗
PubMed1990

Characterization of a transferrin-independent uptake system for iron in HeLa cells.

HeLa cells incubated in serum-free medium accumulated 59Fe ("non-transferrin iron") when incubated with either 59Fe-citrate, 59Fe-nitrilotriacetate, or 59Fe dissolved in Tricine ascorbate. Accumulation of iron was time-, concentration-, and Ca2+-dependent and was saturable. Uptake of non-transferrin (non-Tf) iron was transferrin-independent because of the fact that uptake occurred at pH 5.5, a pH at which transferrin binds iron poorly and at which transferrin is not internalized by cells. Uptake of non-Tf iron was less affected than uptake of transferrin iron by 1) exposure of cells to trypsin, a maneuver that cleaves Tf receptors, or 2) incubation of cells with phenylarsine oxide, an agent that inhibits both fluid- and receptor-mediated internalization. After exposure of cells to non-Tf iron at 37 degrees C, most of the cell-associated radioactivity was recovered in heme and ferritin, demonstrating that iron gained access to intracellular compartments and was not simply adsorbed to the cell surface. Uptake of non-Tf iron could be partially blocked by Cu2+ in a dose-dependent manner, while the accumulation of transferrin-bound iron was unaffected by Cu2+. Other transition metals, such as Zn2+, Cd2+, and Mn2+ were able to inhibit the uptake of non-Tf iron to different degrees. The accumulation of 109Cd was inhibited by incubation of cells with non-Tf iron, Cu2+, or Mn2+. The extent of inhibition was concentration- and metal-dependent. A number of cultured cell lines including HeLa, human skin fibroblasts, and Chinese hamster ovary cells demonstrated uptake of non-Tf iron and 109Cd. Additionally, an endosome acidification mutant of Chinese hamster ovary cells, which exhibited an increase in non-Tf iron uptake, also exhibited an increase in the uptake of Cd2+. These observations suggest that the characteristics of the non-Tf iron transport system in HeLa cells are similar if not identical to those reported for perfused rat liver (Wright, T. L., Brissot, P., Ma, W.-L., and Weisiger, P. A. (1986) J. Biol. Chem. 261, 10909-10914) and suggest the existence of a family of transition metal transport systems, each with a different metal specificity.

Arsenicals↗
PubMed1990

Edinburgh trial of screening for breast cancer: mortality at seven years.

Between 1979 and 1981, 45,130 women in Edinburgh aged 45-64 were entered into a randomised trial of breast cancer screening by mammography and clinical examination. The initial attendance rate was 61% but this varied according to age and socioeconomic status and decreased over succeeding years. The cancer detection rate was 6.2 per 1000 women attending at the first visit; the rate fell to around 3 per 1000 in the years when mammography was routinely repeated and to around 1 per 1000 at the intervening visits with clinical examination alone as the screening method. After 7 years of follow-up the mortality reduction achieved was 17% (relative risk = 0.83, 95% CI 0.58-1.18), which was not statistically significant, even when corrected for socioeconomic status. In women aged 50 years and over a mortality reduction of 20% was achieved.

Age Factors↗
PubMed1990

Herbal remedies.

Explore the source record for details and available documents.

Humans↗
PubMed1990

Antigen presentation by keratinocytes induces tolerance in human T cells.

Antigen recognition by interleukin 2 (IL 2)-producing T lymphocytes can lead to two distinct outcomes, depending on the nature of the antigen-presenting cell. Recognition of antigen presented by specialized antigen-presenting cells leads to T cell activation; in contrast, antigen presentation by cells which lack "accessory function" can lead to a state of specific nonresponsiveness, which is characterized by a failure to produce IL 2. We have shown in this study that co-culture of an HLA-DR1/4-restricted, influenza hemagglutinin-specific T cell clone with a specific peptide presented by interferon-gamma-induced DR4-expressing keratinocytes causes tolerance induction. This effect was DR restricted, in that it required pre-incubation of the T cell clone with keratinocytes expressing an appropriate DR type (DR4Dw14). The induction of T cell tolerance was also antigen specific; no inhibition resulted from pre-incubation of the clone with an irrelevant peptide. Furthermore cell to cell contact appeared to be necessary, and the addition of supernatant from interferon-gamma-induced keratinocytes did not cause any inhibition. This phenomenon may have relevance to the immunogenicity of transplanted cultured keratinocytes and to the effects of major histocompatibility complex class II induction on non-bone marrow-derived cells. Presentation of tissue-specific autoantigens by cells such as keratinocytes may provide a mechanism of avoiding, rather than stimulating, autoimmune reactions in the context of a local inflammatory response.

Antigen-Presenting Cells↗
PubMed1990

Anxiety levels and cancer fear in patients admitted for elective operations.

Patients who are to have elective operations project varying degrees of anxiety, and many spontaneously express fear (without basis) that their operation involves a diagnosis of malignancy. To measure total, covert, and overt anxiety objectively, we gave the Institute for Personality and Ability Testing anxiety test to 125 consecutive patients admitted for elective general surgical procedures. A simple survey of cancer fear was also completed. Chi-square and Fisher's exact test were used to compare categoric data, and linear regression and analysis of variance were used where appropriate. Total anxiety scores were in the upper quartile compared to the general population. Scores indicating fear of cancer were elevated in 75% of patients who had no history of or reason to suspect malignancy. Covert anxiety scores correlated with cancer fear scores, and both significantly decreased as age increased (P less than .05). Also, as age increased, the cancer fear scores decreased (P less than .002). Obese patients had higher scores of cancer fear than all other patients (P less than .0001).

Adult↗
PubMed1990

Expression of the genome of potato leafroll virus: readthrough of the coat protein termination codon in vivo.

An antiserum was raised against a fusion protein containing part of the 56K polypeptide (P5) encoded by the open reading frame (ORF) at the 3' end of the genome of potato leafroll virus (PLRV). This antiserum reacted specifically with 80K and 90K polypeptides in PLRV-infected protoplasts, with a 90K polypeptide in infected potato tissue and with a 53K polypeptide in protein extracted from purified particles of PLRV. Monoclonal antibodies raised against purified PLRV particles also reacted with these polypeptides, as well as with the 23K coat protein. Virus particles partially purified from infected protoplasts contained some 90K polypeptide as well as the major 23K coat protein. The ORFs of the 23K coat protein and P5 are contiguous and in frame. The results suggest that the P5 polypeptide of PLRV occurs in infected cells as part of a readthrough protein comprising the 23K coat protein joined to the P5 amino acid sequence. Moreover the readthrough protein can be assembled into virus particles as a minor component together with the main 23K component. The P5 protein may thus contribute to properties of PLRV determined by its virus particle surface.

Blotting, Western↗
PubMed1990

Guidance for the planning and design of genitourinary medicine clinics.

The number of patients attending genitourinary medicine (GUM) clinics in Britain has risen greatly in recent years. In contrast there have been very modest increases in staff and there are no data on accommodation or facilities. The Department of Health therefore set up a team to provide guidance on the planning and design of GUM clinics. After a survey the team concluded that GUM clinics in England were poorly and inappropriately accommodated. In their guidance they recommended that GUM clinics are sited in general outpatient departments (OPDs) of general hospitals; this improves patient care simplifying cross referral, consultation and other aspects of operational efficiency and convenience for patients, improves cost effectiveness and increases convenience for staff. Some facilities may be shared. Reception should be an attractive focal point and allow patients to be received and registered in privacy. Facilities for clinical examination are the central part of a clinic. Rooms which allow consultation and examination (CE) rooms of male and female patients maximise efficiency, flexibility and confidentiality. Sound attenuation is vital and decor should be attractive so inspiring confidence by producing a non-institutional atmosphere. An adequate number of CE rooms is essential and the waiting area should be sufficient for booked and walk in patients plus companions. There must be rooms for venepuncture, treatment and colposcopy. Interviewing rooms and offices are important, and there must be a secure health records store. A childrens play area and staff accommodation can be shared. An area for handling and simple investigation of patients' specimens is essential. This guidance should be interpreted flexibly. Though commissioned by the Department of Health for England, it is hoped that it will be useful for planning and designing genitourinary medicine clinics throughout Britain and in other countries.

Ambulatory Care Facilities↗
PubMed1990

Differential sensitivity of newborns to synthetic vowel stimuli.

Three-day-old babies were presented with synthetic speech stimuli and some no-sound trials. Three factors of the speech stimuli were examined: vowel quality change, pitch (F0) change, and stimulus presentation rate. The motor behaviour of the neonates was assessed using a multi-response observation method. The babies responded more when the vowel quality changed than when it did not. In some conditions, pitch variation and stimulus presentation rate also affected d'. The work extends previous findings on newborn auditory sensitivity showing differential responding to steady state vowels and that alterations in F0 can affect behaviour. The method has advantages in permitting several stimuli to be compared as well as studying neonates in states of arousal typical of perinatal experience.

Differential Threshold↗
PubMed1990

Identification of a locus which shows no genetic recombination with the autosomal dominant polycystic kidney disease gene on chromosome 16.

The major site for mutations leading to autosomal dominant polycystic kidney disease (ADPKD) is at the PKD1 locus, previously mapped to 16p13. Three additional probes have now been mapped within an existing array of genetic markers flanking this locus. One of these, CMM65b (D16S84), shows no recombination with PKD1 in 201 informative meioses. The others, Fr3-42 (D16S21) and EKMDA2 (D16S83), are shown to be the closest telomeric flanking markers. Somatic cell hybrids containing derivative chromosome 16s were used to construct a physical map of the region. Cosmid overlap cloning of the D16S84 region allowed a t(16;1) translocation breakpoint to be mapped at the molecular level, orientating the extended D16S84 locus with respect to the chromosome. The new markers and physical map described here provide an improved framework for attempts to clone the PKD1 region and to identify polycystic kidney disease mutations.

Animals↗
PubMed1990

Clinical features and molecular analysis of the alpha thalassemia/mental retardation syndromes. I. Cases due to deletions involving chromosome band 16p13.3.

We describe eight patients who have alpha thalassemia which cannot be accounted for by the Mendelian inheritance of abnormal alpha globin genes. Apart from the hematologic abnormality, the other universal clinical finding is mild to moderate mental handicap; there is also a broad spectrum of associated dysmorphic features. Initial analysis of the alpha globin gene complex (which maps to chromosome band 16p13.3), demonstrated that the alpha thalassemia results from failure of the patient to inherit an alpha globin allele from one of the parents. Using a combined molecular and cytogenetic approach, we have extended this analysis to show that all of these patients have 16p deletions which are variable in extent but limited to the terminal band 16p13.3; in at least four cases the deletion results from unbalanced chromosome translocation, and hence aneuploidy of a second chromosome is also present. The relatively nonspecific clinical phenotype contrasts with the other currently known microdeletion syndromes; this may reflect ascertainment bias in the recognition of such syndromes. This work represents the first step in the characterization of a new microdeletion syndrome that is probably underdiagnosed at present.

Adolescent↗