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Biomedical subjects

A Cox

Publications and source records attributed to A Cox.

At least 91 records · Page 5Linked to original sources
PubMed1997

Vascular hypertrophy in experimental diabetes. Role of advanced glycation end products.

The accelerated formation of advanced glycation end products (AGEs) and the overexpression of transforming growth factor beta (TGF-beta) have both been implicated in the pathogenesis of diabetic microvascular and macrovascular complications. Previous studies in our laboratory have demonstrated that the vascular changes in diabetes include hypertrophy of the mesenteric vasculature. To examine the role of AGEs in this process, streptozotocin-induced diabetic rats and control animals were randomized to receive aminoguanidine, an inhibitor of AGE formation, or no treatment. Animals were studied at 7 d, 3 wk, and 8 mo after induction of diabetes. When compared with control animals, diabetes was associated with an increase in mesenteric vascular weight and an increase in media wall/lumen area. By Northern analysis, TGF-beta1 gene expression was increased 100-150% (P < 0.01) and alpha1 (IV) collagen gene expression was similarly elevated to 30-110% compared to controls (P < 0.05). AGEs and extracellular matrix were present in abundance in diabetic but not in control vessels. Treatment of diabetic rats with aminoguanidine resulted in significant amelioration of the described pathological changes including overexpression of TGF-beta1 and alpha1 (IV) collagen. These data implicate the formation of AGEs in TGF-beta overexpression and tissue changes which accompany the diabetic state.

Animals↗
PubMed1997

Suspected nutritional deficiency causing anaemia in llamas (Lama glama).

A case of poor condition and recumbency in a 14-month-old female llama and a case of poor condition and ataxia in a 23-month-old male llama are described. Both animals were anaemic and had low plasma copper levels. An increased intake of feed with a higher copper level and treatment with copper injections and an oral mineral solution resulted in a successful recovery. Two other young llamas also had low plasma copper levels. The problem was probably due to a nutritional, particularly copper, deficiency and the animals recovered as their copper levels increased.

Anemia↗
PubMed1997

Increased epidermal growth factor in experimental diabetes related kidney growth in rats.

Renal enlargement is a characteristic feature of human and experimental diabetes mellitus that may be predictive of subsequent nephropathy. In the streptozotocin diabetic rat kidney growth rapidly follows the induction of experimental diabetes but the mechanisms responsible for this growth are poorly understood. Epidermal growth factor (EGF) is a potent mitogen for renal tubular cells. Thirty one male Sprague-Dawley rats aged 13 weeks were randomised to receive either streptozotocin (diabetic, n = 20) or buffer (control, n = 11). Animals were studied on days 1, 3, 5 and 7 following streptozotocin. Diabetes was associated with a 3-fold increase in urinary EGF excretion (223 +/- 15 vs 59 +/- 5 ng/day, mean +/- SEM, diabetic vs control, p < 0.0001) and 3-6 fold increase in renal EGF mRNA relative to controls (p < 0.001). A transient rise in kidney EGF protein was noted on day 1. There was no difference between diabetic and control animals with regard to intrarenal sites of EGF expression or in plasma EGF. These data suggest that the increased urinary EGF excretion in diabetic animals is the result of enhanced local production and that EGF is not stored for a prolonged period within renal tubular cells but is released following its synthesis. In the context of the known intrarenal actions of EGF this growth factor may play a role in the pathogenesis of diabetes related kidney growth.

Animals↗
PubMed1997

Infants with autism: an investigation of empathy, pretend play, joint attention, and imitation.

Systematic studies of infants with autism have not been previously carried out. Taking advantage of a new prospective screening instrument for autism in infancy (S. Baron-Cohen et al., 1996), the present study found that, compared with developmentally delayed and normally developing children, 20-month-old children with autism were specifically impaired on some aspects of empathy, joint attention, and imitation. Infants with autism failed to use social gaze in the empathy and joint attention tasks. Both the infants with autism and the infants with developmental delay demonstrated functional play, but very few participants in either group produced spontaneous pretend play. In the developmental delay group, but not the autism group, pretend play was shown following prompting. The implications of these findings for developmental accounts of autism and for the early diagnosis of the disorder are discussed.

Analysis of Variance↗
PubMed1997

Transforming growth factor beta 1 and renal injury following subtotal nephrectomy in the rat: role of the renin-angiotensin system.

Transforming growth factor-beta (TGF-beta) and the renin-angiotensin system (RAS) have both been implicated in the pathogenesis of chronic renal disease. The present experiment investigated the chronology of TGF-beta 1 gene expression following subtotal nephrectomy (STNx) in the rat and the effect of blocking the RAS by angiotensin converting enzyme (ACE) inhibition or by angiotensin II receptor (AT1) antagonism. Rats that had undergone subtotal nephrectomy developed hypertension, proteinuria, renal impairement, glomerulosclerosis, tubulointerstitial fibrosis and mononuclear cell infiltration. These changes were associated with a 2.5-fold increase in TGF-beta 1 gene expression during a 16-week time course. In situ hybridization localized TGF-beta 1 mRNA to sclerotic glomeruli, areas of tubuloin-terstitial injury and sites of mononuclear cell infiltration. Administration of the ACE inhibitor ramipril and the AT1 receptor blocker valsartan blunted the increase in TGF-beta 1 mRNA, and attenuated the structural and functional manifestations of injury. These data suggest an interaction between the intrarenal RAS and TGF-beta in the pathogenesis of the glomerular and tubulointerstitial fibrosis that follow a major reduction in renal mass.

Angiotensin II↗
PubMed1997

Sperm morphology assessment: diagnostic potential and comparative analysis of strict or WHO criteria in a fertile and a subfertile population.

This prospective study compared the diagnostic and predictive potential of sperm morphology assessments in a fertile vs. a subfertile population, evaluated in three different laboratories. The fertile population included 144 men who had recently fertilized their partners. As subfertile controls, 136 men with a history of subfertility for more than 12 months were used. All semen samples (280) were evaluated in three different centres in a blind fashion, without any patient information. The evaluation of sperm morphology was performed according to the criteria normally used in the different laboratories: WHO (1992) criteria for laboratory A, and Tygerberg strict criteria for laboratories B and C. Using ROC analysis, the predictive power of sperm morphology turned out to be different in the three laboratories (area under ROC curve: 69% for lab A, 72% for lab B and 78% for lab C). Using percentile 10 of the fertile population as the cut-off value for normality, we obtained the following results: 2, 1 and 5% for laboratories A, B and C, respectively. Using ROC analysis cut-off values with optimal specificity and sensitivity were 6, 1 and 10%, respectively. Although our data highlight a reasonable predictive power of sperm morphology in centres using different or the same criteria, cut-off values for normality were different, even when the same criteria were applied. These results stress the importance of standardization in sperm morphology evaluation and the need for examining a reference population in estimating the real threshold value in different laboratories.

Fertility↗
PubMed1997

The rap and hor proteins of Erwinia, Serratia and Yersinia: a novel subgroup in a growing superfamily of proteins regulating diverse physiological processes in bacterial pathogens.

The enteric bacterium Serratia marcescens is an opportunistic human pathogen. The strain ATCC39006 makes the red pigment, prodigiosin (Pig), and the beta-lactam antibiotic carbapenem (Car). Mutants were isolated that were concomitantly defective for Pig and Car production. These mutants were found to have a mutation in the rap gene (Regulation of Antibiotic and Pigment). Sequence analysis of the rap gene revealed a predicted protein product showing strong homology to SlyA, originally thought to be a haemolytic virulence determinant in Salmonella typhimurium. Homologues of rap were detected in several bacterial genera, including Salmonella, Yersinia, Enterobacter, and species of the plant pathogen, Erwinia. The Erwinia hoeEr (homologue of rap) and the Yersinia horYe genes were also found to be very similar to rap and slyA. Marker exchange mutagenesis of horEr revealed that it encoded a regulatory protein controlling the production of antibiotic and exoenzyme virulence determinants in the phytopathogen, Erwinia carotovora subspecies carotovora. We have shown that these new homologues of SlyA form a highly conserved subgroup of a growing superfamily of bacterial regulatory proteins controlling diverse physiological processes in human, animal and plant pathogens.

Amino Acid Sequence↗
PubMed1997

Semen parameters in a fertile versus subfertile population: a need for change in the interpretation of semen testing.

This prospectively designed study was conducted to compare a fertile and a subfertile population so as to define normal values for different semen parameters. Semen analyses were performed according to the World Health Organization (WHO) guidelines, except for sperm morphology (strict criteria). In the fertile population (n = 144), all patients had recently achieved pregnancy, within 12 months of unprotected coitus. As subfertile controls we examined semen samples from 143 consecutive men attending our infertility clinic during the same study period. Couples with tubal factor infertility and/or ovulatory disorders were excluded from our study. Using receiver operating characteristic (ROC) curve analysis we determined the diagnostic potential and cut-off values for single and combined sperm parameters. Sperm morphology scored best, with a value of 78% (area under the ROC curve). Summary statistics showed a shift towards abnormality for most semen parameters in the subfertile population. Using the 10th percentile of the fertile population as the cut-off value, the following results were obtained: 14.3 x 10(6)/ml for sperm concentration, 28% for progressive motility and 5% for sperm morphology. Using ROC analysis, cut-off values were 34 x 10(6)/ml, 45% and 10% respectively. Cut-off values for normality were different from those described in the WHO guidelines. Routine bacterial and non-bacterial cultures turned out to be of little prognostic value.

Adult↗
PubMed1997

Treatment of male infertility due to sperm surface antibodies: IUI or IVF?

This prospectively designed study was aimed at comparing the results of two different treatment protocols in 29 infertile couples with proven male immunological infertility, i.e. a positive (>50%) mixed antiglobulin reaction (MAR) test (IgG and/or IgA). In the first protocol (group I, n = 14) couples were treated with ovarian stimulation/ intrauterine insemination (IUI), followed by in-vitro fertilization (IVF) if no pregnancy occurred after three IUI cycles. In the second protocol (group II, n = 15), patients were treated with IVF as a first choice procedure. The decision to follow protocol 1 or 2 was made by the couples after information about financial costs and expected success rates (according to the literature) for both treatment options. In group I, nine patients (64.3%) conceived after a maximum of three IUI cycles whereas seven patients (46.6%) of group II became pregnant during the first IVF cycle. The take-home baby rate per started IUI or IVF cycle was 27.3% (9/33) and 44.4% (16/36) respectively with a take-home baby rate of 64.3% after three IUI cycles and 93.3% after three IVF attempts. To conclude, both IUI and IVF yielded unexpectedly high pregnancy rates in this selected group of patients with long-standing infertility due to sperm surface (predominantly IgG) antibodies. Since cost benefit analysis comparing superovulation IUI with IVF may favour a course of four IUI cycles, we advocate superovulation IUI as the first line therapy in male immunological infertility.

Adult↗
PubMed1997

Intrauterine insemination after ovarian stimulation with clomiphene citrate: predictive potential of inseminating motile count and sperm morphology.

This retrospective study aimed to evaluate the prognostic value of the inseminating motile count (IMC) and sperm morphology (using strict criteria) on success rates after homologous intrauterine insemination (IUI) combined with clomiphene citrate (CC) stimulation. A total of 373 couples underwent 792 IUI cycles in a predominantly (87.4%) male subfertility group. The overall cycle fecundity (CF) and baby take-home rate (BTH) was 14.6 and 9.9% respectively. The cumulative CF and BTH (per couple) after three cycles were 30.6 and 21.1% respectively. Overall, sperm morphology and IMC were of no prognostic value using receiver operating characteristic (ROC) curve analysis, but after classifying the study population into different subgroups according to IMC, sperm morphology turned out to be a valuable prognostic parameter in subgroup 1, i.e. IMC <1 x 10(6). In this subgroup, no pregnancies were seen when the morphology score was <4% and the mean value of sperm morphology was significantly different in the pregnant (8.3%) versus non-pregnant group (5.0%; P <0.05). The cumulative CF and BTH after three IUI cycles were comparable for all couples with the exception of those cases in which the IMC was <1 x 10(6) with a morphology score of <4% normal forms. We recorded only two twin pregnancies (2.5%) and no moderate or severe ovarian hyperstimulation syndrome. We conclude that in a selected group of patients without CC resistance and normal ovarian response following CC stimulation [maximum of three follicles with a diameter of >16 mm at the time of administration of human chorionic gonadotrophin (HCG)], IUI combined with CC-HCG can be offered as a very safe and non-expensive first-line treatment, at least with an IMC of >1 x 10(6) spermatozoa. In cases with <1 x 10(6) spermatozoa, CC-IUI remains important as a first-choice therapy provided the morphology score is > or =4%.

Adult↗
PubMed1997

Secreted protein acidic and rich in cysteine expression after subtotal nephrectomy and blockade of the renin-angiotensin system.

Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix-associated protein with antiadhesive, antiproliferative, and matrix remodeling properties. SPARC gene and protein expression were investigated after subtotal nephrectomy (STNx), a model of noninflammatory progressive renal injury. In addition, the effect of blockade of the renin-angiotensin system by the angiotensin-converting enzyme inhibitor ramipril or by the angiotensin II receptor antagonist valsartan was examined. The STNx rats developed hypertension, proteinuria, and renal impairment. These changes were associated with a 2.4-fold increase in SPARC gene expression in STNx compared with SHAM kidneys (P < 0.001). In situ hybridization revealed increased SPARC mRNA in glomeruli and interstitial cells, as well as de novo expression by tubular epithelial cells at sites of renal injury. Immunofluorescence studies confirmed concordant changes in SPARC protein. Both ramipril and valsartan ameliorated renal injury and significantly reduced SPARC overexpression in the STNx animals. The findings of the present study suggest that SPARC, in the context of its known biological actions, may influence some of the pathological features associated with significant renal mass reduction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Effects of mianserin and ketanserin on lordosis behavior after systemic treatment or infusion into the ventromedial nucleus of the hypothalamus.

The effects of the 5-HT2A/2C antagonists, mianserin and ketanserin, were investigated in proestrous rats and in ovariectomized rats hormonally primed with estradiol benzoate and progesterone. Drugs were administered systemically or by infusion into the vicinity of the ventromedial nucleus of the hypothalamus (VMN). By both routes of administration, inhibition of lordosis behavior was seen following treatment with the 5-HT2A/2C antagonists, but the magnitude of the decline was smaller in proestrous than in hormone-primed, ovariectomized rats. The results of these studies are discussed in terms of the dual role of serotonin in the control of female sexual behavior.

Animals↗
PubMed1996

Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus.

We have previously found association between an allele of the interleukin-1 (IL-1) receptor antagonist gene (IL1RN) and several inflammatory diseases, where IL-1 has been implicated in the inflammatory mechanism. We have now, therefore, tested the association of this specific allele (IL1RN*2) with complications of diabetes which have an inflammatory tissue component. We have tested the allele frequency of IL1RN*2 in 128 patients with insulin-dependent and 125 with non-insulin-dependent diabetes mellitus (NIDDM). There was a significant association between carriage of IL1RN*2 and diabetic nephropathy (P<0.001, Pcorrected<0.0012). The association was significant in both types of diabetes, but the observed increase was highest in NIDDM, rising to double the control levels. It appears that IL1RN*2 is a novel genetic marker of severity of inflammatory complications of diseases rather than a marker of disease susceptibility. If the DNA polymorphism is associated with altered gene function, new therapeutic interventions may be possible.

Adult↗
PubMed1996

Novel interleukin-1 receptor antagonist exon polymorphisms and their use in allele-specific mRNA assessment.

A variable number of tandem repeats (VNTR) polymorphism has been described in intron 2 of the interleukin-1 receptor antagonist gene. Allele 2 of this polymorphism is associated with many chronic inflammatory diseases. Using direct sequencing of polymerase chain reaction products from individuals of known genotype for the VNTR, we have identified four single base change polymorphisms in exons 1ic and 2 and one upstream of exon 1ic, all of which are probably in linkage disequilibrium with the intron 2 VNTR. The exonic polymorphisms do not alter the encoded amino acid sequence. Using the exon 2 polymorphism as a marker for the intron 2 disease-associated allele, we have been able to analyse allele-specific mRNA in heterozygotic keratinocyte cell lines. The disease-associated allele shows no difference from other alleles in this cell type with respect to mRNA accumulation.

Alleles↗
PubMed1996

Why pregnant adolescents say they did not use contraceptives prior to conception.

OBJECTIVE: In this study we attempted to learn why childbearing adolescents failed to use contraceptives prior to conception. We hypothesized that among adolescents who elect to bear their children, positive and/or ambivalent feelings about having a baby are the most frequently cited reasons for not having used contraceptives. STUDY DESIGN: This is a cross-sectional, clinic-based survey of a racially and ethnically diverse group of 200 consecutively enrolled, poor, pregnant, 13-18-year-old patients in an adolescent-oriented maternity program. The participants completed a self-administered questionnaire which elicited information about environmental and personal risk factors for inconsistent use of contraceptives and information about the reasons they had not used contraceptives consistently prior to conception. Student's t-tests, Chi-square, and logistic regression analyses were used. RESULTS: The most frequently cited reasons for not using contraceptives prior to conception were: "I didn't mind getting pregnant" (20%) and "I wanted to get pregnant" (17.5%), followed by "I was using birth control but it didn't work (broke)" (12%), "I thought there was something wrong with me and I couldn't get pregnant" (9%) and "I just didn't get around to it" (9%). Teenagers who cited positive and/or ambivalent attitudes toward childbearing as their primary reason for not using contraceptives at the time of conception did not differ from others with regard to age, Medicaid status, gravidity, parity, frequency of living with parents, partner's age, depressive symptoms, or perceived family support. They were, however, more likely to have known the father of the baby for more than 6 months at the time of conception [odds ratio (OR) 2.53; 95% confidence interval (CI) 1.22-5.26) and to have dropped out of school (OR) 2.15; 95% CI 1.10-4.26]. CONCLUSIONS: The study hypothesis was supported. The absence of negative attitudes toward having babies rather than negative attitudes toward contraceptives is the most commonly cited reason for nonuse of contraceptives among childbearing adolescents. The results of this study may enable health care and social service providers to design more effective programs for preventing first and subsequent adolescent pregnancies.

Adolescent↗
PubMed1996

Potential utility of p53 immunopositivity in differentiation of adenocarcinomas from reactive epithelial atypias of the lung.

Reactive atypia of alveolar epithelium occurs in many types of lung injury and may sometimes raise suspicions of adenocarcinoma or bronchioloalveolar carcinoma. To assess whether there is sufficient difference in the frequency of p53 protein immunopositivity in these lesions to provide a practical basis for differentiating malignancy from reactive atypia, we immunostained 110 malignant and inflammatory/fibrotic lung specimens for p53 protein. Paraffin-embedded sections were immunostained with p53 protein antibody (clone BP53-12; BioGenex, San Ramon, CA) and standard capillary gap (Microprobe; Fisher Scientific, Fairlawn, NJ) avidin- biotin complex technique with antigen retrieval solution. Percent of immunopositive cells was semiquantitatively categorized as follows: 0%, less than 1%, 1% to 10%, 10% to 50%, more than 50%. Of reactive atypias, 94% are negative or show p53 immunopositivity in less than 10% of cells. Of p53 positive malignancies, 86% are positive in more than 10% of cells. When p53 immunopositivity occurs in more than 10% of atypical cells, the lesion is usually a malignancy, primarily adenocarcinoma. Most reactive atypias are immunopositive in less than 10% of atypical cells. Important caveats were noted. Rare reactive atypias are p53 immunopositive in greater than 10% of cells. Bronchioloalveolar carcinomas are infrequently p53 immunopositive. Therefore, this approach would be less useful in their differentiation from reactive atypias.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1996

Promotion of children's early psychosocial development through primary health care services.

The paper presents the study design of the development and organisation of an EU/WHO multicentre study on the promotion of children's early psychosocial development through primary health care services. The aim of the programme is to develop training for primary health care workers (PHCWs) that improves their ability to assess factors relevant to psychosocial development and gives them preventive approaches to foster that development, building on families' strengths. The focus is on the period from conception to the end of the second year of the child's' life. Two main components are the training of the PHCWs and the semi-structured interviews that guide the workers in practice. The training has content and structure that is feasible within primary health care resources working in collaboration with mental health services. The programme is evaluated in terms of (a) the impact of training on both the PHCWs' knowledge and attitudes with regard to infant behaviour and development, and on practice as assessed by the delivery of the semi-structured interview; and (b) the effect of the intervention on maternal well-being, infant language development and behavior, home environment and mother-infant interaction. The programme is taking place in Cyprus, Greece, the Federal Republic of Yugoslavia, Portugal, Slovenia and Turkey.

Child Development↗