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Biomedical subjects

D J Lamb

Publications and source records attributed to D J Lamb.

At least 55 records · Page 3Linked to original sources
PubMed1999

Dental student assessment of learning programmes.

OBJECTIVES: To compare relevance, accessibility, role in the teaching-learning process, and user preference, of identical case-study-based teaching programmes in CAL and booklet format. DESIGN: Questionnaire assessment. SUBJECTS AND SETTING: Dental students at Sheffield Dental School. METHODS: 54 5th-year dental students were self-grouped as computer novice (n = 26) or proficient (n = 23) and sub-groups of 12 randomly selected from each. Half of each sub-group tested the CAL programme first and half the booklet-based programme, with cross-over, after 6 weeks. Assessment of packages was carried out immediately after use, and 2 weeks after completion, a further assessment was made on the basis of preference and value as a teaching medium. RESULTS: All subjects thought both packages relevant to clinical practice and written at an appropriate level, and the majority found the text, illustrations and tasks clear. Both groups competed the CAL package more quickly. Students asked to use such packages in the future,viewing them as support for, rather than replacement of, present teaching. The majority of computer-proficient students preferred CAL, considering it the superior teaching medium. CONCLUSIONS: Both CAL and booklet case-study materials were considered useful in addition to, rather than as a replacement for, other teaching methods. Most considered the CAL superior and preferred it. Nevertheless, while past computer experience determined preference for the format, it did not influence ability to access the medium. Future use of such materials is probably best in relation to preparation for tutorials and clinics. A key role is its availability as a revision aid.

Chi-Square Distribution↗
PubMed1999

A C619Y mutation in the human androgen receptor causes inactivation and mislocalization of the receptor with concomitant sequestration of SRC-1 (steroid receptor coactivator 1)

Androgen ablation therapy is a primary treatment for advanced prostate cancer, but tumors become refractive to therapy. Consequently, the role of the androgen receptors (ARs) and of mutations in the AR in prostate cancer has been a subject of much concern. In the course of analyzing tumors for mutations, we identified a somatic mutation that substitutes tyrosine for a cysteine at amino acid 619 (C619Y), which is near the cysteines that coordinate zinc in the DNA binding domain in the AR. The mutation was re-created in a wild-type expression vector and functional analyses carried out using transfection assays with androgen-responsive reporters. The mutant is transcriptionally inactive and unable to bind DNA. In response to ligand treatment, AR619Y localizes abnormally in numerous, well circumscribed predominantly nuclear aggregates in the nucleus and cytoplasm. Interestingly, these aggregates also contain the bulk of the coexpressed steroid receptor coactivator SRC-1, suggesting, in analogy to AR in spinal bulbar muscular atrophy, that this mutant may alter cellular physiology through sequestration of critical proteins. Although many inactivating mutations have been identified in androgen insensitivity syndrome patients, to our knowledge, this is the first characterization of an inactivating mutation identified in human prostate cancer.

Cell Nucleus↗
PubMed1999

An approach to the development of quantitative models to assess the effects of exposure to environmentally relevant levels of endocrine disruptors on homeostasis in adults.

The workshop "Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels" was held to provide a forum for discussions and recommendations of methods and data needed to improve risk assessments of endocrine disruptors. This article was produced by a working group charged with determining the basic mechanistic information that should be considered when designing models to quantitatively assess potential risks of environmental endocrine disruptors in adults. To reach this goal, we initially identified a set of potential organ system toxicities in males and females on the basis of known and/or suspected effects of endocrine disruptors on estrogen, androgen, and thyroid hormone systems. We used this integrated, systems-level approach because endocrine disruptors have the potential to exert toxicities at many levels and by many molecular mechanisms. Because a detailed analysis of all these untoward effects was beyond the scope of this workshop, we selected the specific end point of testicular function for a more detailed analysis. The goal was to identify the information required to develop a quantitative model(s) of the effects of endocrine disruptors on this system while focusing on spermatogenesis, sperm characteristics, and testicular steroidogenesis as specific markers. Testicular function was selected because it is a prototypical integrated end point that can be affected adversely by individual endocrine disruptors or chemical mixtures acting at one specific site or at multiple sites. Our specific objective was to gather the information needed to develop models in the adult organism containing functional homeostatic mechanisms, and for this reason we did not consider possible developmental toxicities. Homeostatic mechanisms have the potential to ameliorate or lessen the effects of endocrine disruptors, but these pathways are also potential target sites for the actions of these chemicals.

Adult↗
PubMed1999

Analysis of homeobox gene HOXA10 mutations in cryptorchidism.

PURPOSE: Cryptorchidism is the most common congenital abnormality of the genitalia. However, its exact etiology remains to be defined. Homeobox (HOX) containing genes have a key role in the morphogenesis of segmental structures along the primary body axis, including the urogenital mesenchyma. In male mice with a targeted deletion of the HOXA10 gene cryptorchidism manifests in the absence of other major defects. Because to our knowledge this gene has never been examined for alterations in humans, we evaluated whether mutations of HOXA10 are associated with cryptorchidism in humans. MATERIALS AND METHODS: Genomic deoxyribonucleic acid (DNA) was extracted from human blood or tissue samples from 16 noncryptorchid control subjects and 45 cryptorchid boys. To screen for mutations exons 1 and 2 of the HOXA10 gene were amplified individually by polymerase chain reaction using 6 overlapping oligonucleotide primer pairs. Single strand conformational polymorphism (SSCP) analysis of the amplified radiolabeled DNA fragments was performed. Variant band shifts were detected due to abnormal migration of the denatured DNA fragment compared to controls, suggesting an alteration in the DNA sequence. Sequence analysis of these variant bands was then done to define any mutations. RESULTS: SSCP analysis revealed variants in 2 controls. Of the 45 samples from cryptorchid patients 30 had SSCP variants in exon 1. No variants were found in other regions of the gene. Sequence analysis revealed several DNA polymorphisms in exon 1 in controls and boys with cryptorchidism. Other nucleotide changes (point mutations) were noted only in exon 1 in the DNA of 5 cryptorchid patients, of whom 1 had a 24 nucleotide deletion. CONCLUSIONS: Our initial analysis of the HOXA10 gene in humans demonstrates that genetic alterations of this gene may be present in some boys with cryptorchidism. HOXA10 polymorphisms exist in normal control subjects as well as in cryptorchid patients. Further analysis of the function of the mutated protein will elucidate the role of this gene as a potential causative factor of testicular descent.

Child↗
PubMed1999

FGF7 and FGF2 are increased in benign prostatic hyperplasia and are associated with increased proliferation.

PURPOSE: To determine if overexpression of FGF7 and FGF2 occurs in benign prostatic hyperplasia (BPH) and if so, whether such overexpression is correlated with increased proliferation of epithelial and/or stromal cells. MATERIALS AND METHODS: The FGF7 and FGF2 content of protein extracts of normal peripheral zone, normal transition zone and hyperplastic prostatic tissues were determined by enzyme-linked immunoabsorption assay. Proliferation of epithelial and stromal cells was assessed by immunohistochemistry with anti-Ki67 antibodies on frozen sections of the same tissues used for protein extraction. The in vitro effects of FGF7 and FGF2 on proliferation were assessed by addition of recombinant growth factor to primary cultures of prostatic epithelial and stromal cells. RESULTS: We have found that both FGF7 and FGF2 are overexpressed in hyperplastic prostate in comparison to normal peripheral and transition zone tissue. FGF7 is a potent mitogen for epithelial cells in culture. Consistent with these in vitro effects, quantitative analysis of cellular proliferation by Ki67 immunohistochemistry revealed a strong correlation of epithelial proliferation with FGF7 content in BPH tissue, consistent with a key role for this growth factor in driving the abnormal epithelial proliferation in BPH. FGF2 is mitogenic for stromal cells in culture and there was a weaker correlation of FGF2 content with increased stromal proliferation. CONCLUSION: Overexpression of FGF7 and FGF2 may play an important role in the abnormal cellular proliferation seen in benign prostatic hyperplasia.

Cell Division↗
PubMed1999

Gender and age-related differences in the pattern of complete denture referrals from general dental practitioners.

This study was designed to identify gender and age-related differences among complete denture referrals from general dental practice to a dental teaching hospital over a 4 year period. Referral rates were calculated according to male/female ratios in the edentulous population. Although more women than men were referred overall, the proportion of males to females referred was similar to that in the edentulous population. Significant gender-related differences in referral patterns were identified, suggesting that edentulous males with complete denture problems, and aged 69 or less, made proportionately less use of hospital services, and proportionately more when aged 70 or over.

Adult↗
PubMed1998

Absence of cyclic adenosine 3':5' monophosphate responsive element modulator expression at the spermatocyte arrest stage.

OBJECTIVE: To test the hypotheses that variations in the expression of adenosine 3':5' monophosphate (cAMP) responsive element modulator are found in human seminiferous epithelium in men with impaired testicular function and subsequent infertility and that variations in apoptosis frequency are associated with differential cAMP responsive element modulator expression in male infertility states. DESIGN: Standard immunohistochemical staining using a rabbit polyclonal antibody against the tau isoform of the cAMP responsive element modulator protein was performed on 5-microM sections of Bouin's fixed, paraffin-embedded testicular tissue obtained from azoospermic or severely oligozoospermic men for routine clinical purposes. Histologic diagnosis was confirmed with computerized image analysis of Feulgen-stained sections. SETTING: Tertiary male infertility referral center at a medical school. PATIENT(S): Forty-eight testis biopsies were performed in 38 azoospermic or severely oligozoospermic males. INTERVENTION(S): Rabbit polyclonal cAMP responsive element modulator tau antibody was applied to the paraffin-embedded testis sections. MAIN OUTCOME MEASURE(S): Testis immunoreactivity to polyclonal cAMP responsive element modulator tau antibody and apoptotic indices. RESULT(S): Although cAMP responsive element modulator immunoreactivity was present in the round spermatid stage of meiosis in testis biopsy specimens showing normal spermatogenesis, spermatid maturation arrest, and hypospermatogenesis, there was complete absence of expression in biopsy specimens from patients with Sertoli cell only and spermatocyte maturation arrest states. In addition, significantly increased apoptotic indices were observed in the spermatocyte maturation arrest state in comparison with normal spermatogenesis and Sertoli cell only pattern. CONCLUSION(S): These data suggest that cAMP responsive element modulator may be important for spermatid development and a stage-specific regulator of human spermatogenesis. Absence of cAMP responsive element modulator may be a cause of testicular failure in various types of male infertility.

Adult↗
PubMed1998

Androgen receptor gene alterations are not associated with isolated cryptorchidism.

PURPOSE: Multiple theories of testicular descent exist but there is no consensus. Cryptorchidism is a component of the androgen insensitivity syndrome, suggesting that testicular descent may be at least partially under the control of androgenic stimulation. To determine whether isolated cryptorchidism may be caused by androgen insensitivity, we screened a population of boys with isolated cryptorchidism for the presence of androgen receptor gene alterations. MATERIALS AND METHODS: Deoxyribonucleic acid (DNA) was isolated from tissue collected from 21 patients with isolated cryptorchidism during orchiopexy. Patient selection was biased to maximize the likelihood of detection of a genetic etiology of cryptorchidism. The DNA was screened for androgen receptor gene alterations in exons 2 to 8 using single strand conformational polymorphism analysis. RESULTS: No abnormalities in the androgen receptor gene were detected by single strand conformational polymorphism analysis in any patient. CONCLUSIONS: Mutations of the androgen receptor gene in the hormone and DNA binding domains of the protein appear to be an unlikely cause of isolated cryptorchidism.

Child↗
PubMed1998

Restorative treatment need assessment by dentally and nondentally trained subjects.

A study was carried out which compared how two groups of people, one with clinical dental experience and one without, assessed restorative dental treatment need. Using a visual analogue scale, a group of final year dental students (n = 50) and nonclinical university students (n = 50) assessed the extent to which they considered common dental imperfections, viz. spacing of the upper anterior teeth and discolouration of upper anterior teeth, warranted restorative correction. The group of dental students judged the necessity for treatment of discolouration to be more urgent than correction of spacing. The nondental group did not differentiate between the degrees of need. Data were non-normal in distribution but the use of appropriate statistical tests showed the differences in mean assessments to be significant.

Adolescent↗
PubMed1998

Genetic concerns for the subfertile male in the era of ICSI.

The treatment of severe male factor infertility has seen remarkable advances in the last five years with the introduction and widespread use of intracytoplasmic sperm injection (ICSI). Although ICSI represents one of the most important advances in the treatment of the subfertile male, significant concerns exist regarding the potential for transmission of abnormal genes to the offspring because many of the natural barriers to conception have been bypassed. Because these couples were not able to conceive prior to ICSI, the long-term genetic consequences in these offspring are largely undefined at this time. Genetic abnormalities related to male infertility need to be considered in terms of being (1) causative for male infertility and (2) potentially transmissible to the offspring. Reasons for pursuing a genetic evaluation include (1) establishing a diagnosis, (2) establishing a possible genetic origin, (3) clarifying the pattern of inheritance, and (4) providing information on natural history, variation and expression. The three most common known genetic factors related to male infertility are cystic fibrosis gene mutations leading to congenital absence of the vas deferens, Y-chromosome microdeletions leading to spermatogenic impairment, and karyotype abnormalities. When congenital bilateral absence of the vas deferens with azoospermia is encountered, cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations are commonly the underlying cause. When testicular failure is manifest by azoospermia or severe oligoszoospermia, Y-chromosome microdeletions may be present in approximately 10-15 per cent of otherwise normal appearing men. Karyotyping can uncover potentially transmissible genetic abnormalities in the infertile male including structural chromosomal disorders such as Klinefelter's (classic 47,XXY), mixed gonadal dysgenesis, chromosomal translocations and XYY syndromes. Finally, potential male infertility genes in animal models are reviewed. Without question, advances in clinical and basic research raise scientific and social issues that must be addressed.

Animals↗
PubMed1997

Non-oxidative modification of low density lipoprotein by ruptured myocytes.

In this study, the interaction of ruptured cardiac myocytes with low density lipoprotein (LDL) has been investigated and the consequent extent of uptake by macrophages. The results show that lysate released from ruptured myocytes is capable of inducing LDL oxidation and that the resulting modified form is recognised and degraded by macrophages. Peroxyl radical scavengers inhibit the LDL oxidation but not the macrophage uptake suggesting that LDL can be modified by mechanisms that are independent of oxidative processes by intracellular constituents of cardiac myocytes.

Animals↗
PubMed1997

In situ end-labeling of human testicular tissue demonstrates increased apoptosis in conditions of abnormal spermatogenesis.

OBJECTIVE: To determine, using an in situ end-labeling technique, whether the frequency of apoptosis is increased in testis biopsy specimens that demonstrate abnormal spermatogenesis. DESIGN: Immunohistochemical analysis was performed on archived paraffin-embedded testis biopsy specimens. Apoptotic indices, defined as the number of apoptotic bodies per the total number of cells or the number of Sertoli cells, were calculated after counting all the intratubular spermatogenic cells and Sertoli cells in 20 tubules. SETTING: Major academic male factor infertility clinic. PATIENT(S): Forty-eight testis biopsy specimens were obtained for routine clinical purposes from 38 men with azoospermia or severe oligozoospermia. INTERVENTION(S): In situ end-labeling was performed on archived paraffin-embedded testis biopsy specimens using terminal deoxynucleotidyl transferase. MAIN OUTCOME MEASURE(S): Apoptotic indices. RESULT(S): Significantly increased apoptotic indices were observed in patients with spermatocyte arrest, spermatid arrest, and hypospermatogenesis compared with patients with normal spermatogenesis and the Sertoli cell-only pattern. CONCLUSION(S): In situ end-labeling of testis biopsy specimens from infertile men demonstrates increased apoptosis in maturation arrest and hypospermatogenesis states compared with normal spermatogenesis and the Sertoli cell-only pattern. This unique observation implicates a prominent role for this form of programmed cell death in the pathophysiology of maturation arrest and hypospermatogenesis states.

Adult↗