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D J Lamb

Publications and source records attributed to D J Lamb.

At least 19 recordsLinked to original sources
PubMed2006

Association between indices of body mass and antibody titres to heat-shock protein-60, -65 and -70 in healthy Caucasians.

We have previously shown that antibody titres to several heat-shock proteins (Hsps) are elevated in dyslipidaemic patients and subjects with established vascular disease. Obesity is known to be associated with raised serum inflammatory markers suggesting a state of heightened immune activation. Hence, we have investigated the association between indices of obesity and several Hsp antibody titres in healthy subjects. Subjects (n=170) were recruited from among employees at the University of Surrey and the Royal Surrey County Hospital, Guildford, UK. Of these subjects, 35 were obese with a body mass index (BMI)>/=30 kg/m(2) (19 male and 16 female subjects), 58 were overweight with 30>BMI>/=25 kg/m(2) (36 male and 22 female subjects) and 77 were of a normal weight with BMI<25 kg/m(2) (31 male and 46 female subjects). Overall, obese subjects had significantly higher plasma anti-Hsp-60 (P<0.001), anti-Hsp-65 (P<0.05) and anti-Hsp-70 (P<0.05) compared with overweight and normal weight subjects.

Antibodies↗
PubMed2006

Characterization of the putative cholesterol transport protein metastatic lymph node 64 in the brain.

Intracellular management of cholesterol is a critical process in the brain. Deficits with cholesterol transport and storage are linked to neurodegenerative disorders such as Neimann-Pick disease type C and Alzheimer's disease. One protein putatively involved in cholesterol transport is metastatic lymph node 64 (MLN64). MLN64 localizes to late endosomes which are part of the cholesterol internalization pathway. However, a detailed pattern of MLN64 expression in the brain is unclear. Using immunocytochemical and immunoblot analyses, we demonstrated the presence of MLN64 in several tissue types and various regions within the brain. MLN64 immunostaining in the CNS was heterogeneous, indicating selective expression in discrete specific cell populations and regions. MLN64 immunoreactivity was detected in glia and neurons, which displayed intracellular labeling consistent with an endosomal localization. Although previous studies suggested that MLN64 may promote steroid production in the brain, MLN64 immunoreactivity did not colocalize with steroidogenic cells in the CNS. These results demonstrate that MLN64 is produced in the mouse and human CNS in a restricted pattern of expression, suggesting that MLN64 serves a cell-specific function in cholesterol transport.

Animals↗
PubMed2005

An SNP in protamine 1: a possible genetic cause of male infertility?

Gene targeting of the sperm nuclear proteins, the protamines, in mice leads to haploinsufficiency, abnormal chromatin compaction, sperm DNA damage, and male infertility. In order to investigate whether changes in amount or structure of the protamines could be a cause of human infertility, we sequenced the protamine genes of infertile men whose sperm appeared phenotypically similar to those of protamine deficient mice. We identified a heterozygous single nucleotide polymorphism (SNP) in the protamine (PRM1) gene in three infertile men (10% of the total infertile men analysed). This SNP disrupts one of the highly conserved arginine clusters needed for normal DNA binding. To rapidly screen for this SNP in infertile patients, we developed a simple PCR restriction fragment length polymorphism assay. This is the first report of a SNP in the PRM1 gene that appears associated with human male infertility.

Amino Acid Sequence↗
PubMed2005

Plasma antibody titres to heat shock proteins-60, -65 and-70: their relationship to coronary risk factors in dyslipidaemic patients and healthy individuals.

OBJECTIVE: To investigate the factors that may affect antibody titres to heat shock proteins (Hsp)-60, -65 and -70, and serum C-reactive protein (CRP) concentrations in patients with dyslipidaemia and other features of the metabolic syndrome as defined by ATPIII criteria. MATERIAL AND METHODS: The study comprised 237 dyslipidaemia patients and 135 healthy individuals recruited from amongst university and hospital employees. RESULTS: Compared to the healthy individuals, the dyslipidaemic patients had higher antibody titres to Hsp-60 (p<0.01), Hsp-65 (p<0.001) and Hsp-70 (p<0.05), and higher serum CRP concentrations (p<0.001). The best-fitting multifactorial models revealed that known coronary risk factors explained little of the variation in Hsp antibody titres: 3 % for Hsp-60, 1 % for Hsp-65 and 4 % for Hsp-70 amongst the dyslipidaemic subjects. The corresponding values for the subgroup with the metabolic syndrome were 8 %, 3 % and 1 %, respectively. In contrast, the best-fitting model explained 13.5 % of the variation in serum CRP concentrations among the dyslipidaemic patients, obesity being a major determinant; and 14 % in the subgroup with metabolic syndrome. CONCLUSIONS: The higher antibody titres to Hsp-60, -65, and -70 in the dyslipidaemic patients may be related to a heightened state of immunoactivation associated with atherosclerosis in this group. Our data indicate that antibody titres to these Hsps are not associated with the classical coronary risk factors, although serum high sensitivity (hs)CRP concentrations were significantly related to obesity.

Antibodies↗
PubMed2005

Palatal discrepancies and postdams.

To investigate the variation in post-cure palatal discrepancy of dentures, 20 complete maxillary replica dentures were prepared on models with high and low palates and processed by conventional compression moulding and injection moulding. Measurements were made by travelling microscope of the sagittal midline discrepancies between palate and model on three occasions; after processing; after removal of part of the investing plaster; and after immersion in water for 1 month at 37 degrees C. The magnitudes of discrepancies were greatest distally, diminishing with distance anteriorly from the postdam. They increased with partial removal of plaster, and decreased slightly after immersion.

Acrylic Resins↗
PubMed2005

Determinants of serum copper, zinc and selenium in healthy subjects.

BACKGROUND: We have investigated the association between serum copper, zinc and selenium concentrations, dietary intake, and demographic characteristics, including individual coronary risk factors, in healthy subjects. METHODS: Serum copper, zinc and selenium were measured by atomic absorption spectrometry in 189 healthy subjects. Serum glutathione peroxidase and caeruloplasmin were also determined for each subject. A previously validated food frequency questionnaire was used to estimate the dietary trace element intake. RESULTS: Male subjects had significantly lower serum copper (P<0.001) and caeruloplasmin (P<0.001), and higher serum zinc (P<0.05) and zinc:copper ratio (P<0.001) than female subjects. Significant differences were observed in serum copper and caeruloplasmin concentrations (P<0.01) with age. Weak but significant associations between dietary trace elements and their serum concentrations were observed for zinc (r=0.18, P=0.02), copper (r=0.17, P=0.03) and selenium (r=0.19, P=0.02). Obese subjects had significantly lower serum concentrations of zinc (P<0.05). In multifactorial analysis, dietary zinc (P<0.05), serum high-density lipoprotein-cholesterol (HDL-C) (P<0.05), diastolic blood pressure (P<0.05) and age (P=0.05) emerged as major predictors of serum zinc concentrations. The corresponding predictors for serum copper were C-reactive protein (CRP) (P<0.001), serum HDL-C (P<0.001), gender (P=0.01), physical activity levels (P<0.05) and dietary copper (P<0.05). Serum selenium concentrations were predicted by serum total cholesterol (P<0.01), serum CRP concentrations (P<0.05) and dietary selenium (P<0.03). CONCLUSION: Serum copper, zinc and selenium concentrations are influenced by physiological conditions such as age, diet and gender. Their serum concentrations are also associated with coronary risk factors, including body mass index, levels of physical activity, serum HDL-C and CRP.

Adult↗
PubMed2004

What does the lipoprotein oxidation phenomenon mean?

The evidence that oxidative lipid modification may be involved in the genesis of common diseases, such as atherosclerosis, is persuasive, but it was, until recently, conjecture based on in vitro findings, or investigation using experimental animal models. Recent clinical intervention studies in patients at high risk of cardiovascular events have been, at best, inconclusive. This has led to a general consensus that antioxidant supplements are of no value in the prevention of cardiovascular disease in subjects at high risk. However, epidemiological studies have demonstrated that the protective effects of antioxidant supplements, specifically vitamin E, were particularly evident amongst healthy subjects taking supplements. The picture is further clouded by the uncertain mechanism of lipoprotein modification within the artery wall, the possibility that some antioxidants may, under certain conditions, become pro-oxidants, the complex interactions between lipid- and water-soluble antioxidants, and the fact that free-radical-mediated events may only be important in the early stages of atherogenesis. Recent results also suggest that the biological efficacy of antioxidants, such as alpha-tocopherol, may be compromised by the conditions extant within the plaque. It is evidently important that the position on the benefits of antioxidants, whether in food or as supplements, in disease prevention is clarified.

Animals↗
PubMed2003

Microsatellite instability and defects in mismatch repair proteins: a new aetiology for Sertoli cell-only syndrome.

Microsatellite instability is characteristic of certain types of cancer, and is present in rodents lacking specific DNA mismatch repair proteins. These azoospermic mice exhibit spermatogenic defects similar to some human testicular failure patients. Therefore, we hypothesized that microsatellite instability due to deficiencies in mismatch repair genes might be an unrecognized aetiology of human testicular failure. Because these azoospermic patients are candidates for testicular sperm extraction and ICSI, transmission of mismatch repair defects to the offspring is possible. Seven microsatellite loci were analysed for instability in specimens from 41 testicular failure patients and 20 controls. Blood and testicular DNA were extracted from patient and control specimens, and amplified by PCR targeting seven microsatellite loci. DNA fragment length was analysed with an ABI Prism 310 Genotyping Machine and GeneScan software. Immunohistochemistry was performed on paraffinized testis biopsy sections and cultured testicular fibroblasts from each patient to determine if expression of the mismatch repair proteins hMSH2 and hMLH1 was normal in both somatic and germline cells. Results demonstrate that microsatellite instability and DNA mismatch repair protein defects are present in some azoospermic men, predominantly in Sertoli cell-only patients (P < 0.01 and P < 0.05 respectively). This provides evidence of a previously unrecognized aetiology of testicular failure that may be associated with cancer predisposition.

Animals↗
PubMed2002

Implant treatment.

Explore the source record for details and available documents.

Alveolar Bone Loss↗
PubMed2001

Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: molecular markers of risk for male infertility.

OBJECTIVE: To determine whether changes in the polymorphic trinucleotide (CAG) tract of the androgen receptor gene are associated with spermatogenic defects in patients with male infertility. DESIGN: Case-control study of two ethnic groups. SETTING: University referral centers for male infertility at Baylor College of Medicine, Houston, Texas, and National University Hospital, Singapore. PARTICIPANT(S): Two hundred and fifteen patients with male infertility and depressed spermatogenesis and 142 fertile controls. MAIN OUTCOME MEASURE(S): Size of androgen receptor CAG alleles according to fluorescent-labeled polymerase chain reaction and automated analysis using Genescan software (PE Biosystems Asia, Singapore), and statistical examination of its relation to clinical variables. RESULT(S): In U.S. patients, the mean androgen receptor CAG length was significantly longer in infertile patients than in fertile controls (21.95 +/- 0.31 vs. 20.72 +/- 0.52). Logistic regression showed that each unit increase in CAG length was associated with a 20% increase in the odds of being azoospermic. The odds ratio for azoospermia was sevenfold higher for patients with > or =26 CAG repeats than in those with <26 CAG repeats. Although mean CAG length in Singapore patients was longer than in the U.S. samples, long androgen receptor CAG alleles were significantly related to male infertility in both populations. CONCLUSION(S): Long (> or =26) androgen receptor CAG alleles, which are found in up to 25% of azoospermic men, are associated with male infertility and defective spermatogenesis. Conception in these men is possible with assisted reproductive technologies, as many have spermatozoa in their testes.

Biopsy↗
PubMed2001

Increased chromosome X, Y, and 18 nondisjunction in sperm from infertile patients that were identified as normal by strict morphology: implication for intracytoplasmic sperm injection.

OBJECTIVE: To determine the incidence of nondisjunction for chromosomes X, Y, and 18 using fluorescence in situ hybridization (FISH) on morphologically normal sperm from infertile men who are candidates for ICSI. DESIGN: After standard hematoxylin staining, sperm with normal morphology were identified using Kruger's strict morphology criteria. The location of each normal-appearing sperm was recorded using an electronic microstage locator. Slides were subsequently subjected to FISH for detection of chromosomes X, Y, and 18 (control probe). Nuclei were relocated and analyzed under the fluorescent microscope. SETTING: University-affiliated IVF and intracytoplasmic sperm injection program. PATIENT(S): Men classified as infertile on the basis of abnormal strict morphology (<4% by Kruger's criteria). For controls, normal fertile men (n=6) were also analyzed. INTERVENTION(S): Semen smears were obtained retrospectively from infertile (n=8) and fertile (n=6) men. MAIN OUTCOME MEASURE(S): Ploidy of each cell was determined according to the number of signals detected for each probe. RESULT(S): Approximately 100-150 morphologically normal sperm were identified and located in each case. Subsequent FISH analysis of these normal sperm showed aneuploidy to range from 1.8% to 5.5% in the infertile group as compared with 0 to 2.6% among the control fertile group. Statistically significant differences in the incidence of aneuploidy for the sex chromosomes as well as for all three (X, Y, and 18) chromosomes was observed. CONCLUSION(S): Although 95% to 98% of the sperm were found to be normal for X, Y, and 18, our findings show that infertile couples undergoing ICSI are likely to be at an increased risk for having a genetically abnormal conceptus as compared with the fertile controls. These results demonstrate that normal morphology is not an absolute indicator for the selection of genetically normal sperm. Hence, observed pregnancy failures among ICSI patients may in part be due to the selection of aneuploid sperm.

Adult↗
PubMed2001

Modification of natural and artificial polymer colloids by "topology-controlled" emulsion polymerization.

A diffuse layer of water-soluble polymer chemically grafted to the surface of a hydrophobic polymer colloid has been created by the second-stage polymerization of dimethylaminoethyl methacrylate (DMAEMA) onto the biomacromolecule polyisoprene in natural rubber latex and also onto synthetic polybutadiene and polystyrene latexes. To control the locus of radical formation, the process was initiated by a redox couple wherein one component (e.g., cumene hydroperoxide) is hydrophobic and the other (e.g., tetraethylenepentamine) is hydrophilic. The modified latexes displayed a dramatic increase in colloidal stability at low pH which is attributed to grafted hydrophilic polymer acting as an electrosteric stabilizer; the effect is particularly remarkable in natural rubber latex, which usually has poor colloidal stability for pH less, similar 8. (13)C NMR was performed to verify the existence of the grafted copolymer and to quantify yield. The mechanism by which such a novel morphology can be generated is postulated to be via a process of radical formation at the particle surface followed by the subsequent grafting to the hydrophobic polymer backbone and polymerization of hydrophilic monomer in the aqueous phase. This technique is potentially useful for creating novel materials from natural rubber latex.

Butadienes↗
PubMed2001

Biphasic modulation of atherosclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit.

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. We have investigated the effects of graded dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Rabbits (n = 40) were fed a 0.25-1% cholesterol diet deficient in copper. Animals received either 0, 1, 3 or 20 mg copper/day and were killed after 13 weeks. Plasma cholesterol levels were similar in each dietary group. Aortic concentrations of copper were higher in the 20 mg copper/day animals compared to those receiving 0 mg copper/day (3.70 +/- 0.78 vs. 1.33 +/- 0.46 microg/g wet tissue; P < 0.05). Aortic superoxide dismutase activity was higher in animals receiving 20 mg copper/day (323 +/- 21 IU/mg tissue) compared to the other groups (187 +/- 21; 239 +/- 53; 201 +/- 33 IU/mg tissue) (P > 0.05). En face staining of aortae with oil red O showed that both high copper supplementation (20 mg/day) (67.1 +/- 5.5%) and a deficient diet (0 mg/day) (63.1 +/- 4.8%) was associated with significantly larger lesions (P < 0.05) compared to moderately supplemented animals (1 mg/day and 3 mg/day) (51.3 +/- 6.3 and 42.8 +/- 7.9%). These data indicate that in the cholesterol-fed rabbit, there is an optimal dietary copper intake and that dietary copper deficiency or excess are associated with an increased susceptibility to aortic atherosclerosis. Many Western diets contain insufficient copper and these findings indicate that a moderate dietary copper content may confer a degree of cardiac protection to the human population.

Animals↗
PubMed2001

Defects of dental appearance assessed by patient and dental student groups.

A study was carried out to establish the relative need for treatment of a range of defects of dental appearance and identify differences between individual and group assessments. Three groups (n = 42), two of patients (one referred for a defect of dental appearance and one not) and one of dental students, assessed urgency of need on a visual analogue scale (VAS), of four cases of dental defect presented as colour prints. All groups rated the need for treatment of the four cases in the same order. Data sets were non-normal with wide ranges. Patients without a defect of appearance usually assessed treatment need as significantly less urgent. Marked variation was discovered between individual assessments within otherwise similar groups. Based on group decisions, guidelines for treatment of defects of dental appearance could be established. However, so extreme are individual variations that very sympathetic application would be needed if dissatisfaction is not to result.

Adolescent↗
PubMed2001

Genetic effects of intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) must be proved safe as well as efficacious. In this communication we first review available data following ICSI pregnancies concerning frequency of spontaneous abortion, malformations, and chromosomal abnormalities. In ICSI the spontaneous abortion rate is slightly increased, just as it is in in vitro fertilization (IVF) without ICSI. Among 6077 ICSI cycles begun in 1997 in the United States, there were 17.5% pregnancy losses. The same cohort showed a malformation rate of 1.7% in live-born infants. Malformations in live-born infants are not increased: 1.7% in the United States and 2.3% in Brussels. However, the Swedish IVF Registry encompassing 1139 ICSI infants found hypospadias to be increased (relative risk 2.9, 95% C.I. 1.4 to 5.4). Birth weight and prematurity rate in ICSI pregnancies seem similar to that following conventional IVF without ICSI. The category of genetic defects for which concerns have most often been raised is chromosomal abnormalities. A cohort of 1987 pregnancies in Brussels yielded a frequency of de novo autosomal rearrangements of 0.36% and a de novo sex chromosomal abnormalities of 0.83%. Both rates are higher than expected in the general population. Various explanations for these increased cytogenetic autosomal abnormalities are explored in this communication. In addition to arising from the procedure per se, a genetic or cytogenetic abnormality in offspring of an ICSI pregnancy could arise as result of offspring inheriting the mutant gene or chromosomal abnormality conferring paternal infertility: Y deletions (DAZ) in oligospermia males, cystic fibrosis in offspring of males with congenital bilateral absence vas deferens (CBAVD), and sex chromosomal abnormalities in offspring of Klinefelter syndrome (47,XXY) males.

Abortion, Spontaneous↗
PubMed2001

Endogenous neutralizing antibodies against platelet-derived growth factor-aa inhibit atherogenesis in the cholesterol-fed rabbit.

Previous studies have shown that the B chain of platelet-derived growth factor (PDGF) has an important role in atherogenesis. In this study we have investigated the contribution of PDGF-A chain in cholesterol-induced atherogenesis in the New Zealand White rabbit. High titers of antibodies to PDGF-AA or to platelet cytosolic protein (PCP) were induced in these animals by immunization against recombinant human PDGF-AA or human PCP. Rabbits were then fed a 0.25% to 1% cholesterol-containing diet for 10 weeks to induce atherosclerotic lesions; the rabbits were then humanely killed and perfusion-fixed and their aortas were removed. The extent of atherosclerosis in the thoracic aortas was determined by quantitative morphometry after staining with oil red O. The intimal and medial areas in histological sections taken at the level of the first intercostal branch were quantified by image analysis. Immunization against PDGF-AA and PCP, but not against adjuvant alone, resulted in rising titers of antibodies within 2 weeks, the levels of which reached a plateau by 8 weeks. The antibodies to PDGF-AA were isoform-specific, recognized both human and rabbit PDGF-AA, and neutralized the biological activity of PDGF-AA in vitro. Integrated plasma cholesterol levels were similar in both groups. Compared with nonimmune rabbits (n=10), animals immunized against PDGF-AA (n=10) or PCP (n=10) had significantly smaller areas of the aorta covered by atherosclerotic lesions (24.6+/-5.1% and 18.7+/-4.2%, respectively, vs 34.4+/-4.3%; P<0.05). This was associated with a reduced aortic intimal-medial area ratio in PDGF-AA-immunized (0.009+/-0.006) and PCP-immunized (0.025+/-0.017) rabbits than in nonimmune animals (0.159+/-0.066; P<0.05). These data suggest that PDGF-AA is actively involved in cholesterol-induced atherosclerosis in the rabbit.

Animals↗