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Biomedical subjects

J Lamb

Publications and source records attributed to J Lamb.

At least 37 records · Page 2Linked to original sources
PubMed1999

Renal cell carcinoma with massive osseous metaplasia and bone marrow elements.

Focal calcifications are frequently seen in renal masses and may be present in renal cell carcinomas. Metaplastic bone formation, on the other hand, is a rare event. We report a unique case of a large calcified renal cell carcinoma with massive osseous metaplasia and bone marrow elements. The clinical and pathologic differential diagnosis for this tumor is discussed along with a review of the literature on this unusual phenomenon.

Biomarkers, Tumor↗
PubMed1999

A quantitative-trait locus on chromosome 6p influences different aspects of developmental dyslexia.

Recent application of nonparametric-linkage analysis to reading disability has implicated a putative quantitative-trait locus (QTL) on the short arm of chromosome 6. In the present study, we use QTL methods to evaluate linkage to the 6p25-21.3 region in a sample of 181 sib pairs from 82 nuclear families that were selected on the basis of a dyslexic proband. We have assessed linkage directly for several quantitative measures that should correlate with different components of the phenotype, rather than using a single composite measure or employing categorical definitions of subtypes. Our measures include the traditional IQ/reading discrepancy score, as well as tests of word recognition, irregular-word reading, and nonword reading. Pointwise analysis by means of sib-pair trait differences suggests the presence, in 6p21.3, of a QTL influencing multiple components of dyslexia, in particular the reading of irregular words (P=.0016) and nonwords (P=.0024). A complementary statistical approach involving estimation of variance components supports these findings (irregular words, P=.007; nonwords, P=.0004). Multipoint analyses place the QTL within the D6S422-D6S291 interval, with a peak around markers D6S276 and D6S105 consistently identified by approaches based on trait differences (irregular words, P=.00035; nonwords, P=.0035) and variance components (irregular words, P=.007; nonwords, P=.0038). Our findings indicate that the QTL affects both phonological and orthographic skills and is not specific to phoneme awareness, as has been previously suggested. Further studies will be necessary to obtain a more precise localization of this QTL, which may lead to the isolation of one of the genes involved in developmental dyslexia.

Adolescent↗
PubMed1999

Chromosome size-dependent control of meiotic reciprocal recombination in Saccharomyces cerevisiae: the role of crossover interference.

In the yeast Saccharomyces cerevisiae, small chromosomes undergo meiotic reciprocal recombination (crossing over) at rates (centimorgans per kilobases) greater than those of large chromosomes, and recombination rates respond directly to changes in the total size of a chromosomal DNA molecule. This phenomenon, termed chromosome size-dependent control of meiotic reciprocal recombination, has been suggested to be important for ensuring that homologous chromosomes cross over during meiosis. The mechanism of this regulation was investigated by analyzing recombination in identical genetic intervals present on different size chromosomes. The results indicate that chromosome size-dependent control is due to different amounts of crossover interference. Large chromosomes have high levels of interference while small chromosomes have much lower levels of interference. A model for how crossover interference directly responds to chromosome size is presented. In addition, chromosome size-dependent control was shown to lower the frequency of homologous chromosomes that failed to undergo crossovers, suggesting that this control is an integral part of the mechanism for ensuring meiotic crossing over between homologous chromosomes.

Chromosomes, Fungal↗
PubMed1999

Health concerns and risk behaviors of rural adolescents.

Although much has been written about the health status of adolescents, little is known about adolescents' perception of their own health. The purpose of this article is to describe the health concerns of rural adolescents. Two national studies, the Youth Risk Behavior Survey and the National Longitudinal Study of Adolescent Health (Add Health Project), are used as comparisons. Data from the rural survey represent 624 community adolescents attending 4 rural Pennsylvania schools. The students were in the 9th, 10th, and 11th grades. The Adolescent Health Inventory was used to report concerns related to general health, psychosocial issues, and risk behaviors. Overall, rural adolescents in the study reported an average of 6.5 (SD = 3.2) health concerns with frequencies of occurrence being always or often and reported an average involvement in 1 (SD = 1.3) risk behavior. Psychosocial issues were reported by 28%, and 23% worried about their general health. Frequently reported risk behaviors included alcohol use, drug use, and a lack of exercise. There was minimal concern expressed regarding venereal disease or AIDS, whereas 12% expressed concern about the possibility of pregnancy. These results suggest the likelihood that adolescents perceive health from a holistic perspective and that health promotion programs should consider involving adolescents in planning, both (a) to ensure congruence of the plan of care with adolescents' concerns and (b) to clarify the interpretation and meaning of their concerns. We present implications for the community health nurse.

Adolescent↗
PubMed1999

Pain management. A patient's perspective.

Improving pain management practices can decrease adverse complications and improve patient outcomes. This in turn will result in the more efficient use of health care resources. Clinicians who are constantly challenged to improve delivery of care are interested in the perceptions of patients. They often rely on their patients' reported levels of satisfaction as an outcome measure for success of a program. Most often, informal methods are used to gather information on satisfaction with care.

Adolescent↗
PubMed1998

Six unrelated HLA-DR-matched adults recognize identical CD4+ T cell epitopes from influenza A haemagglutinin that are not simply peptides with high HLA-DR binding affinities.

Influenza A/Beijing/32/92 (H3N2) haemagglutinin (HA)-specific short-term CD4+ T cell lines were generated from six unrelated HLA-DR0701, 1501 positive adults (aged 27-60 years) 3 months following administration of an influenza subunit vaccine containing HA A/Beijing/32/92. Epitope recognition was examined using 118 HA A/Beijing/32/92-specific 16mer peptides which overlapped by 11 residues and which spanned the entire molecule. Following influenza vaccination the donors recognized identical HA peptides. The selected peptides represented HA regions which have been free from extensive drift mutation since the emergence of human H3N2 influenza A strains. Using DAP DR7.0701 cells (a murine cell line expressing HLA-DR0701) as antigen-presenting cells the majority of CD4+ T cell responses were shown to be HLA-DR0701 restricted. The relationship between HA peptide recognition and relative strength of HA peptide-HLA-DR0701 binding was then explored in a competition assay with biotinylated CLIP peptide. Although peptides representing dominant HA epitopes bound to DR0701, the relationship between relative strength of binding and immunodominance was complex, and many strongly binding peptides, particularly those with glycosylation sites and showing inter-strain variation, were not recognized. These results illustrate the control HLA class II exerts over CD4+ T cell HA epitope selection in unrelated adult humans. Immunodominance appears not to be directly related to the relative strength of HA peptide-HLA class II binding, and thus reflects complex interactions between antigen processing, intracellular competition for HLA binding, TCR repertoires and repeated exposure to different strains of influenza A viruses.

Adult↗
PubMed1998

Systemically but not orogastrically delivered insulin-like growth factor (IGF)-I and long [Arg3]IGF-I stimulates intestinal disaccharidase activity in two age groups of suckling rats.

The growth mitogenic properties of IGF-I on tissues of the gastrointestinal tract are well established; however, IGF effects on enzyme maturation are less clear. To test whether IGF-I peptide administration stimulates disaccharidase activity, we administered IGF-I or the more potent analog, long [Arg3]IGF-I, at doses ranging between 2 and 12.5 micrograms g-1 d-1 to suckling Wistar rat pups by either continuous s.c. infusion or by three times daily orogastric gavage. Peptides were administered for approximately 6 d starting on d 6 or 12 postpartum with six to nine rats per group. The results of the study demonstrated that systemically but not orally administered IGF-I stimulated duodenal wet tissue weight (up to 85%) and length (up to 36%). Enzyme maturation was assessed by measuring disaccharidase biochemically in tissue homogenates. Enzyme activity was also localized histocytochemically in cryostat-sectioned duodenum. After systemic infusion of IGF-I, intestinal lactase activity increased proportional to mucosal mass in both age groups. Systemic infusion of the more potent analog, long [Arg3]IGF-I, precociously induced the decline in lactase activity and accelerated the appearance of sucrase activity in the rat pups infused during the later suckling period. These findings indicate that enzyme maturation can be accelerated by systemically derived IGF-I peptides. Orogastrically IGF-I peptides, delivered at pharmacologic doses, did not affect intestinal growth or digestive enzyme maturation in suckling rat pups treated between 6 and 18 d postpartum, indicating the efficacy of IGF-I peptides may depend on the route of delivery and postnatal age of the recipient.

Administration, Oral↗
PubMed1998

Cell cycle-independent death of prostate adenocarcinoma is induced by the trk tyrosine kinase inhibitor CEP-751 (KT6587).

Advanced prostate cancer remains largely incurable, primarily because the very low growth fraction present in these tumors makes them generally resistant to treatment with standard chemotherapeutic agents that target cell division. Effective therapies should therefore induce death of prostate cancer cells, independent of their growth rate. trkA, the high-affinity tyrosine kinase-linked receptor for nerve growth factor, has been implicated in prostatic cancer growth and may represent a molecular target for therapeutic agents. At low mg/kg doses, the trk tyrosine kinase inhibitor CEP-751 (KT6587) inhibits prostatic cancer growth in nine different animal models independent of the tumor growth rate, androgen sensitivity, metastatic ability, or state of tumor differentiation. CEP-751 is selective for cancerous versus normal prostate cells and affects the growth of only a limited number of nonprostate tumors. Importantly, CEP-751 induces cell death of prostate cancer cells in a cell cycle-independent fashion and, therefore, represents a novel therapeutic approach to the management of both hormone-dependent and hormone-independent prostate cancer.

Adenocarcinoma↗
PubMed1997

Apoptosis in colorectal carcinoma occurring in patients aged 45 years and under: relationship to prognosis, mitosis, and immunohistochemical demonstration of p53, c-myc and bcl-2 protein products.

The aim of this study was to ascertain whether apoptotic counts have prognostic significance in colorectal cancer and if such counts are related to the expression of proteins implicated in cell cycle regulation. Material from a cohort of patients aged 45 years or less with colorectal carcinoma was re-examined to determine apoptotic and mitotic counts by light microscopy, in addition to assessing p53, c-myc, and bcl-2 protein status by immunohistochemistry. The apoptotic index in the 74 patients who were alive or who had died of colorectal carcinoma ranged from 1.2 per cent to 12.3 per cent and exhibited independent prognostic significance, with high counts predicting better survival (P = 0.02). Mitotic counts were not related to survival, despite a close correlation with apoptosis (r = 0.85). Tumours regarded as not staining with the CM1 antibody for p53 protein demonstrated higher apoptotic counts, compared with those that stained (medians 5.2 and 4.0 per cent, respectively; P = 0.03), but p53 expression was found not to be related to survival. The 68 tumours which stained for c-myc appeared to exhibit higher mitotic counts than those that did not. bcl-2 was detected in only four tumours. The latter two proteins exhibited no apparent relationship to the apoptotic index or survival. Although these results indicate a potential role for apoptotic counting in prognostic prediction in colorectal tumours, this is an uncommon group of patients who exhibited some atypical features. The likelihood of a proportion of cases arising within hereditary non-polyposis colorectal cancer syndrome may limit the application of the findings to a more general population with cancer of the colon and rectum. Further work is required, including critical measurement of reproducibility and assessment of the relative impact of this parameter compared with 'traditional' prognostic markers.

Adolescent↗
PubMed1997

IL-5 production by allergen-stimulated T cells following grass pollen immunotherapy for seasonal allergic rhinitis.

Grass pollen immunotherapy for the treatment of seasonal allergic rhinitis ('summer hayfever') results in improvement in symptoms, a reduction in the early and late phase responses to allergen provocation and decreased tissue eosinophilia. Immunotherapy may act by altering the pattern of cytokine production by allergen-specific T cells from a 'Th2-type' (IL-4 and IL-5) profile to a 'Th1-type' (interferon-gamma (IFN-gamma)) profile. We set out to determine whether clinical improvement following specific allergen immunotherapy is accompanied by reduced production of the pro-eosinophilic and archetypal 'Th2-type' cytokine, IL-5. Peripheral blood mononuclear cells (PBMC) were isolated from (i) 13 patients who had received 6 or 7 years' continuous conventional immunotherapy with timothy grass pollen (Phleum pratense); (ii) 14 patients who had received 3 or 4 years of conventional immunotherapy followed by 3 years of placebo treatment; (iii) 12 matched seasonal rhinitic patients who had never received immunotherapy; and (iv) 17 non-atopic normal controls. PBMC were stimulated with 20 microg/ml and 200 microg/ml P. pratense extract, or 10 microg/ml of Mycobacterium tuberculosis purified protein derivative (PPD), at 2 x 10(6) cells/ml and 5 x 10(6) cells/ml. IL-5 concentrations in culture supernatants collected after 6 days' culture were measured by ELISA. IL-5 production in response to stimulation with P. pratense extract was highly reproducible and was elevated in both of the immunotherapy treated groups and the untreated rhinitics relative to non-atopic controls (P<0.005 for each group relative to non-atopic controls, under each of the four conditions tested). However, no significant reduction was observed in IL-5 production when immunotherapy treated patients were compared with untreated rhinitic controls. Moreover, abrogation of the cutaneous late-phase responses to allergen following treatment was not associated with reduced IL-5 production by allergen-stimulated peripheral blood T cells. Reduced IL-5 production by peripheral blood T cells may not be necessary for immunotherapy to be effective. Local immunodulation of T cell responses may play a role in this form of treatment.

Adult↗
PubMed1996

From epitopes to peptides to immunotherapy.

Allergic inflammatory responses are regulated by cytokines [interleukin (IL)-4, IL-5, IL-10, and IL-13] produced by CD4+ helper (Th0 and Th2) cells. The activation of these T cells follows engagement of T-cell antigen receptors (TCR) by antigenic peptides complexed with major histocompatibility complex (MHC) class II molecules. Under defined conditions presentation of T-cell epitopes as peptides can downregulate immune responses, and here we discuss the potential of peptide-mediated immunotherapy in the regulation of responses to the house dust mite (HDM). Cloning the major allergens of HDM has allowed detailed analysis of the HDM-reactive T-cell repertoire and has revealed that MHC class II restriction is heterogeneous, involving HLA-DP,-DQ, and -DR molecules, and that multiple T-cell epitopes are recognized. There is, however, evidence for a bias in TCR gene usage, which has prompted the analysis of peptide-mediated densitization of human T cells in vitro. CD4+ T cells exposed to high concentrations of HDM peptides become refractory to restimulation and fail to provide B-cell help. This is accompanied by complex changes in the surface phenotype, including the downregulation of TCR and CD28. During the induction of anergy cytokine-specific mRNA levels are enhanced, but when the anergic T cells are restimulated they fail to secrete IL-4 and IL-5, although interferon (IFN)-gamma production may remain unaltered. The ability of peptides to modulate the function of HDM-specific T cells in vivo has been investigated in mice. Following inhalation of peptide containing a major T-cell epitope of Der p 1 (residues 111-139) transient T-cell activation was observed prior to the inhibition of responses in naive and sensitized mice. T cells from the tolerant mice restimulated in vitro produced low levels of cytokines and failed to provide help for B cells.

Adjuvants, Immunologic↗
PubMed1996

Imidazoacridinones arrest cell-cycle progression in the G2 phase of L1210 cells.

Imidazoacridinones are a new class of highly potent antineoplastic agents synthesised at the Technical University of Gdansk. The pharmacophoric alkyldiamine group, which is also present in anthracenediones (e.g. ametantrone, mitoxantrone), has been shown to be responsible for their antineoplastic activity. In view of their chemical similarity to anthracenediones, we anticipated that the imidazoacridinones would have a mechanism of action similar to that of these agents and that this would be reflected by a similar influence on cell-cycle progression. Flow cytometry was used to monitor the effect of three derivatives of imidazoacridinone (C-1263, C-1310 and C-1311) on L1210 cell cycle traverse at concentrations ranging from 0.01 to 0.9 microgram/ml, corresponding to their 50% and 90% effective concentrations (EC50 and EC90 values), over times of drug treatment ranging from 1 to 48 h. The results demonstrate that all of the compounds produced a similar effect, inducing preferential and complete arrest (accumulation) of cells in the G2 phase of the cell cycle (i.e. G2 block). The kinetics of the induction of G2 arrest were dependent on both the dose and the duration of treatment. Cell-cycle arrest was reversible for up to about 3 h of treatment, being quite irreversible at longer incubation times. Microscopic inspection of cells performed in parallel with flow cytometry confirmed that imidazoacridinones induced a G2, not a G2/M, block.

Aminoacridines↗
PubMed1996

Cell killing by the novel imidazoacridinone antineoplastic agent, C-1311, is inhibited at high concentrations coincident with dose-differentiated cell cycle perturbation.

We have studied the actions of C-1311, an imidazoacridinone analogue with potent in vivo antitumour activity, against a human tumour line (HeLa S3), in an examination of the events associated with the lethality of this agent. Continuous exposures (24 h) induced complete G2 arrest, although the concentration range of this effect was narrow, with elevation of the drug level inducing additional and increasing impediment to S-phase transit. Acute treatments (3 h) revealed that cells exposed to drug levels, which first induced persistent G2 arrest (0.5 microgram ml-1), subsequently died from this compartment, while doses exceeding these levels (1.0 microgram ml-1), paradoxically, did not cause the same extensive cell death. We explain our findings on the proposition that this particular mode of cell death is dependent upon inappropriate activation of the primed mitotic machinery-specifically the hyperphosphorylated p34cdc2/cyclin B complex-assembled within G2, but that impediment to genomic replication at higher doses inhibits assembly of this complex, and hence prevents cell death. Our results demonstrate that high dose does not necessarily correlate with increased cell death, while at the same time providing further evidence for the importance of events normally associated with the G2/M transition in DNA damage-induced tumour cell death.

Aminoacridines↗
PubMed1996

Assessment of the acceptability of conservative management of fibroadenoma of the breast.

A prospective study was performed in 202 patients with 219 fibroadenomas, diagnosed by a combination of clinical examination, ultrasonography and fine-needle aspiration cytology. Patients were given the choice of excision or conservative management with regular monitoring by ultrasonography. Sixteen patients with 18 fibroadenomas opted for excision and all 18 lesions were histologically confirmed as fibroadenomas. A further 152 patients with 163 fibroadenomas were observed for a minimum period of 2 years; 13 fibroadenomas increased significantly in size (all 13 were excised and confirmed histologically as fibroadenomas), 19 decreased significantly in size, 42 resolved and the remaining 89 showed no change in size. Conservative management of fibroadenomas in patients under the age of 40 is safe and acceptable to the majority of women.

Adult↗