Viewpoint interview--Ron Paul.
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Automation↗
Biomedical subjects
R Paul
Publications and source records attributed to R Paul.
P-Cadherin is a basal cell-specific epithelial marker that is not expressed in prostate cancer.
P-Cadherin is a member of the cadherin family of cell surface glycoproteins that mediate Ca2+-dependent cell-cell adhesion and is expressed in a differential fashion in normal epithelial tissues. The expression of P-cadherin in human prostate cancer development has not been investigated previously. By immunohistochemistry, we show that P-cadherin expression is restricted to the cell-cell border of basal epithelial cells in 30 normal prostate samples. This staining is down-regulated in prostatic intraepithelial neoplasia and is absent in all 25 of the well to poorly differentiated prostate cancer specimens analyzed. To examine potential P-cadherin-regulatory elements, we sequenced the 5'-flanking region of this gene. Similar to the mouse gene, the human P-cadherin promoter is TATA-less, contains an Sp-1 binding site and, analogous to the human E-cadherin sequence, demonstrates a GC-rich region characteristic of a CpG island. Cytosine methylation of this region occurs in P-cadherin-negative prostate cancer cell lines but not in cell lines expressing this gene. In vivo, a lack of expression in 12 clinical prostate cancer specimens is not associated with methylation of the P-cadherin promoter. These results demonstrate that the expression of the basal cell marker P-cadherin is lost in prostate cancer development and that in vivo mechanisms other than cytosine methylation regulate this consistent loss of expression.
Animals↗
Rare metastases of signet ring cell carcinomas to the scrotum: report of two cases.
Metastases of signet ring cell carcinomas to the scrotum are rare. We present 2 patients with this kind of tumor. In 1 patient, the scrotal pathologic examination helped to detect an adenocarcinoma of the appendix with a signet ring cell component, with an extent that had not been apparent clinically. The other patient was seen at an advanced stage of signet ring cell carcinoma of the sigmoid colon following surgical therapy and palliative chemotherapy. The route of metastases seems to be via seeding along the testicular cord and via lymphatic dissemination.
Appendiceal Neoplasms↗
Narrative development in late talkers: early school age.
Children with slow expressive language development (SELD) as toddlers and a control group of children with normal language development (NL) were followed to early school age. Children with SELD were, at that point, subdivided into two groups: those who had moved within the normal range of expressive language (the History of Expressive Language Delay [HELD] subgroup); and those who continued to score below the normal range in expressive language at school age (the Expressive Language Delay [ELD] subgroup). During their kindergarten, first, and second grade years, they were administered a narrative generation task. Narratives were analyzed for MLU, lexical diversity, amount of information included, proportion of complete cohesive ties, and overall stage of narrative maturity. In kindergarten, children with normal language history scored significantly higher than those with HELD and ELD on lexical diversity and narrative stage; and higher than those with ELD in proportion of complete cohesive ties. In first grade, children with normal language history again scored significantly higher than those with HELD and ELD on narrative maturity, with no other significant differences. In second grade, there were no significant differences among the groups.
Age Factors↗
Coding sequence and chromosome mapping of the human gene (CDC46) for replication protein hCdc46/Mcm5.
We have isolated the complete cDNA sequence encoding the human homolog of the yeast replication protein Cdc46/Mcm5. The cDNA was used as a probe for chromosomal fluorescence in situ hybridization (FISH), which localized the human Cdc46 gene (CDC46) to chromosome region 22q13.1-->q13.2. This is the fourth human Mcm gene whose chromosome region has been determined, and it is now apparent that human Mcm genes are widely distributed in the genome. As deduced from the cDNA sequence, human protein hCdc46 is composed of 734 amino acids and contains a central region that is almost 80% identical with the yeast protein. Immunoprecipitation experiments with hCdc46-specific antibodies confirm that essentially all nuclear hCdc46 proteins form a stable dimeric complex with protein P1Mcm3.
Amino Acid Sequence↗
Rapid mapping of mitochondrial dna deletions by large-fragment PCR.
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Base Sequence↗
Mediastinal enterogenic cyst presenting as paraplegia--a case report.
A rare case of a mediastinal enterogenic cyst with an intraspinal extension through a anterior vertebral defect presenting with paraplegia in a 10 year boy is presented. Laminectomy and the trans-thoracic excision of the cyst resulted in the complete recovery of the neural deficit.
Abnormalities, Multiple↗
Experimental pneumococcal meningitis: cerebrovascular alterations, brain edema, and meningeal inflammation are linked to the production of nitric oxide.
We investigated whether treatment with the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA) and the free radical scavenger superoxide dismutase influences cerebral blood flow changes, brain edema, and cerebrospinal fluid pleocytosis in early experimental pneumococcal meningitis. Compared to untreated infected rats, superoxide dismutase given 3 hours after infection significantly attenuated the increase of brain water content, intracranial pressure, and cerebrospinal fluid white blood cell count, but did not modulate the increase in regional cerebral blood flow. N-Nitro-L-arginine treatment (5 mg/kg intravenously, followed by 5 mg/kg/hour) reversed the increase in regional cerebral blood flow; prevented an increase in brain water content, intracranial pressure, and cerebrospinal fluid nitrite concentrations; and reduced cerebrospinal fluid white blood cell count. With a closed cranial window preparation, N-nitro-L-arginine prevented pneumococci-induced dilatation of pial arterioles. When the effective dose was increased twofold, the effects of N-nitro-L-arginine became more pronounced but resulted in the death of 4 of 5 rats, probably due to hemodynamic side effects. In primary cultures of rat cerebral endothelial cells, nitrite concentrations increased after pneumococcal stimulation, which could be prevented by N-nitro-L-arginine and cycloheximide. These data suggest that (a) nitric oxide accounts for regional cerebral blood flow changes and pial arteriolar dilatation in the early phase of experimental pneumococcal meningitis; (b) both superoxide radical and nitric oxide are involved as mediators of brain edema and meningeal inflammation; and (c) cerebral endothelial cells can be stimulated by pneumococci to release nitric oxide presumably via the inducible nitric oxide synthase.
Amino Acid Oxidoreductases↗
Pharmacokinetics and metabolism of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in mammary tumors of antiestrogen-treated rats.
Attempts are being made to evaluate 2-[18F]fluoro-2-deoxy-D-glucose (FDG) as a noninvasive marker of therapy response in malignant tumors. We studied rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinomas by measuring the differential absorption ratio (DAR) and the metabolites of FDG in tumor homogenates. Half the rats were treated with the antiestrogen toremifene for 14 days and half were untreated. The histology of the tumors was studied by morphometry. The animals were killed 15, 45 or 240 min after injection. Regardless of whether the rats received toremifene or not, the fractional change in tumor volume correlated better with the DAR at 15 min [r = 0.284 (untreated) and r = 0.721 (treated)] and at 240 min [r = 0.932 (untreated)], than at 45 min [r = -0.137 (untreated) and r = 0.265 (treated)]. Inverse relations were found for the fraction of unmetabolized FDG and change in tumor volume [r = 0.070 (45 min) and r = -0.872 (240 min) for untreated tumors and r = -0.963 (15 min) and r = -0.715 (45 min) for treated tumors]. The DAR and the fraction of unmetabolized FDG correlated also [r = -0.420 (15 min), r = -0.647 (45 min) and r = -0.976 (240 min) for untreated tumors, and r = -0.963 (15 min) and r = -0.213 (45 min) for treated tumors]. No significant therapy-induced morphometrical changes were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
9,10-Dimethyl-1,2-benzanthracene↗
Complex carpal dislocation.
We present an unusual case of carpal dislocation which to our knowledge has not previously been described in any of the current classifications of such injuries. Despite the extensive damage sustained, the case was managed without difficulty and outcome has been very satisfactory.
Carpal Bones↗
Questions concerning facilitated communication: response to Duchan.
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Autistic Disorder↗
Disseminated acyclovir-resistant herpes simplex virus type 2 treated successfully with foscarnet.
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Acyclovir↗
Prostate-specific antigen density and age-specific prostate-specific antigen values: the solution of prostate cancer screening?
The results of 225 systematic prostate biopsies from 1992 to 1993 were evaluated retrospectively. The parameters prostate-specific antigen (PSA) density and age-specific PSA values were compared with digital rectal examination, transrectal ultrasound, and PSA as single parameters and possible combinations. The PSA density proved to have the highest specificity of all single parameters, but the sensitivity was low. Age-specific PSA values are offering a good compromise of sensitivity and specificity as compared with fixed cutoff levels. Since there is no sufficient screening parameter up to now, a combination of all parameters is recommended for screening of early prostate cancer.
Aged↗
The challenge of marketing wellness programs to small versus large firm employees.
The authors extend prior research by examining employee attitudes towards wellness programs among thirty-eight large and small companies in five states. Program components that were considered to be most desirable by workers at different sized companies are identified in a series of regression models. The results indicate that different sized firms can emphasize general wellness and aerobic exercise programs during the design phase of employee wellness programs. However, employees at large companies were more interested in early detection programs than small firm employees.
Attitude to Health↗
Marketing hospital wellness products to service companies.
The authors examine service firm employee attitudes towards wellness programs among twenty-three service companies in three states. Program components that were considered to be most desirable by service industry workers are identified in a regression model. The results indicate that hospital administrators need to adopt a marketing approach during the design phase of employee wellness programs.
Attitude to Health↗
Neonatal pulmonary mechanics and oxygenation after prophylactic amnioinfusion in labor: a randomized clinical trial.
OBJECTIVE: Amnioinfusion has been reported to improve the perinatal outcome of pregnancies complicated by decreased amniotic fluid volume, but detailed information on its possible adverse effects on neonatal pulmonary mechanics and oxygenation is not available. STUDY DESIGN: We evaluated 42 infants with birth weights of 2600 to 4320 g and gestational ages of 36 to 44 weeks, who were born to mothers enrolled in a prospective, randomized trial of amnioinfusion for oligohydramnios in labor. Maternal entry criteria were gestational age 36 weeks or older, estimated fetal weight more than 2500 g, oligohydramnios defined as an amniotic fluid index of 5 cm or less, and a normal fetal heart rate pattern. Evaluation of pulmonary mechanics and oxygen saturation (SaO2) was done with the infants breathing room air between birth and day 3 of life. Transpulmonary pressure, flow, and tidal volume were recorded simultaneously, and pulmonary resistance and lung compliance were calculated. SaO2 was measured for 30 minutes with the Nellcor N-200 oximeter and IBM computer oximetry software. RESULTS: Evaluation of the data revealed no significant difference between the two groups for tidal volume, lung compliance, pulmonary resistance, or work of breathing. There were no differences between the two groups in the number of desaturation episodes or in percent of desaturations to less than 90%, 85%, or 80% SaO2. CONCLUSION: Prior studies have shown amnioinfusion to improve perinatal outcome. Our findings demonstrate that amnioinfusion for oligohydramnios in labor does not adversely affect neonatal pulmonary mechanics or oxygenation.
Amnion↗
HIV-1 prevalence and risk factors among sexually transmitted disease clinic attenders in Trinidad.
OBJECTIVES: To study trends in prevalence and to ascertain risk factors for HIV-1 among sexually transmitted disease (STD) clinic attenders in Trinidad. DESIGN AND METHODS: Serial cross-sectional studies were conducted in 1987-1988 and 1990-1991 at a centralized STD clinic in Port of Spain. A case-control study was carried out to examine in greater detail the demographic and behavioral risk factors for HIV-1 among self-declared heterosexuals in this population. RESULTS: HIV-1 prevalence increased from 3.0% [95% confidence interval (CI), 2.3-3.9] in 1987-1988 to 13.6% (95% CI, 11.8-15.6) in 1990-1991. Age > or = 40 years [odds ratio (OR), 2.0; 95% CI, 1.4-2.8], urban residence (OR, 2.2; 95% CI, 1.6-3.0), and human T-lymphotropic virus-I seropositivity (OR, 3.1; 95% CI, 1.6-6.0) were significant risk factors for HIV-1 in 1990-1991. In the case-control analysis, significant independent risk factors for men included current genital ulcer disease (OR, 5.2; 95% CI, 2.2-12.5), current genital warts (OR, 3.9; 95% CI, 1.2-12.0), having ever had syphilis (OR, 3.2; 95% CI 1.6-6.1), and use of crack cocaine in the preceding 6 months (OR, 6.2; 95% CI, 2.7-14.2). Corresponding risk factors for women were commercial sex work (OR, 5.7; 95% CI, 1.3-25.7), initiation of sexual activity before age 14 years (OR, 4.8; 95% CI, 1.5-16.0), and past non-gonococcal cervicitis (OR, 4.1; 95% CI, 1.3-13.1). CONCLUSIONS: HIV-1 in this setting is primarily heterosexually transmitted in a milieu of unprotected sexual activity fuelled by a crack cocaine epidemic. Targeted interventions to prevent, detect and treat STD and crack cocaine addiction, as well as disrupt their adverse synergism, may substantially reduce HIV-1 transmission in this population.
Adult↗
Tris: an allosteric effector of tarantula haemocyanin.
The effect of the chemical buffering component Tris (hydroxy-methyl-amino-methane) and of chloride ions on the oxygen binding of tarantula hemocyanin was studied at constant pH. It revealed that Tris at micromolar concentrations decreases the oxygen pressure at half-saturation (p50) by a factor of more than two, whereas chloride does not influence oxygen affinity. A thermodynamic analysis in terms of the nested model of allostery [(1987) Proc. Natl. Acad. Sci. 84, 1891-1895] indicated that Tris acts a an allosteric activator of oxygen binding by influencing the interaction between the 12-meric half-molecules of the 24-meric tarantula haemocyanin.
Allosteric Regulation↗