PubMed Health⌕ Search

Biomedical subjects

J D Brooks

Publications and source records attributed to J D Brooks.

At least 55 records · Page 3Linked to original sources

Molecular biology of prostate cancer progression.

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns (summarized in Fig. 1). The most consistent changes seen are those of allelic loss events, with the majority of tumours examined showing loss of alleles from at least one chromosomal arm. The short arm of chromosome 8, followed by the long arm of chromosome 16, seem to be the most frequent regions of loss, suggesting the presence of novel tumour suppressor genes. Deletions of one copy of the RB and TP53 genes are less frequent as are mutations of the TP53 gene, and accumulating evidence suggests the presence of an additional tumour suppressor gene on chromosome 17p, which is frequently inactivated in prostate cancer. Alterations in the E-cadherin/alpha catenin mediated cell-cell adhesion mechanism appear to be present in almost half of all prostate cancers and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. Finally, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting widespread alterations in methylation modulated gene expression. The presence of multiple changes in these tumours is consistent with the multistep nature of the transformation process. Finally, efforts to identify prostate cancer susceptibility loci are under way, which may elucidate critical early events in prostatic carcinogenesis.

Cadherins↗

Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis.

Hypermethylation of regulatory sequences at the locus of the pi-class glutathione S-transferase gene GSTP1 was detected in 20 of 20 human prostatic carcinoma tissue specimens studied but not in normal tissues or prostatic tissues exhibiting benign hyperplasia. In addition, a striking decrease in GSTP1 expression was found to accompany human prostatic carcinogenesis. Immunohistochemical staining with anti-GSTP1 antibodies failed to detect the enzyme in 88 of 91 prostatic carcinomas analyzed. In vitro, GSTP1 expression was limited to human prostatic cancer cell lines containing GSTP1 alleles with hypomethylated promoter sequences; a human prostatic cancer cell line containing only hypermethylated GSTP1 promoter sequences did not express GSTP1 mRNA or polypeptides. Methylation of cytidine nucleotides in GSTP1 regulatory sequences constitutes the most common genomic alteration yet described for human prostate cancer.

Carcinoma↗

Laparoscopic management of testicular pain after embolotherapy of varicocele.

We report a patient who underwent embolization of a varicocele for chronic testicular pain with Gianturco coils and developed increased bilateral pain. Complete pain relief was achieved by laparoscopic resection of both spermatic cords. The case provides insights into the pathophysiology of testicular pain and may suggest alternative therapies for chronic orchialgia.

Adult↗

Genetic alterations in prostate cancer.

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns (summarized in Fig. 1). To date, the most consistent changes are those of allelic loss events, with the majority of tumors examined showing loss of alleles from at least one chromosomal arm. The short arm of chromosome 8, followed by the long arm of chromosome 16, appear to be the most frequent regions of loss, suggesting the presence of novel tumor suppressor genes. Deletions of one copy of the Rb and p53 genes are less frequent, as are mutations of the p53 gene, and accumulating evidence suggests the presence of an additional tumor suppressor gene on chromosome 17p, which is frequently inactivated in prostate cancer. Alterations in the E-cadherin/alpha-catenin-mediated cell-cell adhesion mechanism appear to be present in almost half of all prostate cancers and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. Finally, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting widespread alterations in methylation-modulated gene expression. The presence of multiple changes in these tumors is consistent with the multistep nature of the transformation process. Finally, efforts to identify prostate cancer susceptibility loci are under way and may elucidate critical early events in prostatic carcinogenesis.

Cadherins↗

Molecular biology of prostate cancer.

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns (summarized in Fig 1). To date, the most consistent changes are those of allelic loss events, with the majority of tumors examined showing loss of alleles from at least one chromosomal arm. The short arm of chromosome 8, followed by the long arm of chromosome 16 appear to be the most frequent regions of loss, suggesting the presence of novel tumor suppressor genes. Deletions of one copy of the Rb and p53 genes are less frequent as are mutations of the p53 gene, and accumulating evidence suggests the presence of an additional tumor suppressor gene on chromosome 17p, which is frequently inactivated in prostate cancer. Alterations in the E-cadherin/alpha catenin mediated cell-cell adhesion mechanism appear to be present in almost half of all prostate cancers, and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. Finally, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting widespread alterations in methylation-modulated gene expression. The presence of multiple changes in these tumors is consistent with the multistep nature of the transformation process. Finally, efforts to identify prostate cancer susceptibility loci are underway and will hopefully elucidate critical early events in prostatic carcinogenesis.

Cadherins↗

Determination of physicochemical properties of phenol, p-nitrophenol, acetone and ethanol relevant to quantitating their percutaneous absorption in porcine skin.

A knowledge of the rate and extent of chemical absorption across the skin is central to both transdermal drug delivery and cutaneous toxicology. Toward gaining sufficient insight into the relevant mechanisms involved in percutaneous absorption of topically applied agents in solution to validate a predictive model, we have 1) estimated porcine stratum corneum/water partition coefficients of two 14C-labeled compounds of interest (phenol and p-nitrophenol), and 2) measured dynamic surface evaporation from dosed excised porcine skin of these two radiolabeled compounds and two 14C-labeled commonly employed vehicles (acetone and ethanol). The surface evaporation profiles were fit to a kinetic model designed to estimate the liquid/vapor parameters for application to a general biophysically-based model of percutaneous absorption. In an effort to obtain more robust estimates of model parameters, corresponding evaporation experiments were effected on the isolated perfused porcine skin flap (IPPSF) under the same experimental conditions. Stratum corneum/water partition coefficients were determined for phenol and p-nitrophenol using a stratum corneum preparation from excised porcine integument.

Acetone↗

Tubularized neourethra following radical retropubic prostatectomy.

A 1.5 cm. tubularized neourethra was formed using an anterior bladder flap as part of bladder neck reconstruction after radical retropubic prostatectomy in 69 consecutive patients with clinically localized prostate cancer (study group). Postoperative continence (defined as requiring no protection for any activity) was assessed by history at 3 months (all men) and 6 months (45 of 69 men). Continence in the study group was compared to that of 45 men with 6 months of followup who underwent radical retropubic prostatectomy without tubularization of the anterior bladder (control group). At 3 months 38 of 69 men (55%) were continent in the study group and 14 of 45 (31%) were continent in the control group (p < 0.03). At 6 months 39 of 45 men (87%) were continent in the study group compared to 21 of 45 (47%) in the control group (p < 0.01). Upright cystograms performed on men with and without the tubularized neourethra after radical retropubic prostatectomy suggest that a neourethra proximal to the external sphincter may increase resistance in this area and result in early return of urinary control in men undergoing radical retropubic prostatectomy.

Aged↗

Tumor suppressor gene allelic loss in human renal cancers.

It is now apparent that multiple genetic alterations, including oncogene activation and tumor suppressor gene inactivation, are necessary steps in carcinogenesis. We have studied this concept in renal cancers by looking at specific tumor suppressor genes implicated in several allelotyping studies. Primary, predominantly low stage renal tumors of varying grades and histologic subtypes were investigated for allelic loss of 3p, 17p and the p53 gene, the DCC gene and the Rb gene and its product. 3p loss occurred in 47% of tumors studied and was much more common in clear cell cancers (85%). 17p and p53 gene loss were relatively uncommon events with only 6 of 42 tumors demonstrating loss. None of the tumors with typical histologies had allelic loss of the DCC gene, though loss did occur in leiomyosarcoma and a collecting duct tumor. Allelic loss of the Rb gene occurred in one clear cell tumor, the leiomyosarcoma, and, interestingly, in both collecting duct tumors in this series. Allelic loss of the Rb gene was correlated with little or no RB protein expression as judged by immunohistochemistry. At all loci studied, allelic loss did not appear to correlate with tumor grade or stage. These results suggest that inactivation of the p53, Rb, and DCC genes by allelic loss are uncommon events in the early stages of renal carcinogenesis.

Blotting, Southern↗

The Beck Depression Inventory: item order and the impact of response sets.

The lack of subtle content in the item groups of the Beck Depression Inventory (BDI) and the consistency in the ordering of the items from least to most pathological make this instrument unduly susceptible to either defensive or malingering response sets. Two experimental forms were developed for the BDI: a backwards version (a simple reversal of the order of items within each group) and a random-order version. These forms, together with the original item order, were given to college undergraduate women along with the Depression scale from the MMPI and the Burks-Martin Questionnaire covering recent life changes and current stressful situations. The random order BDI results in a significantly higher depression score than did either the original or backwards version. Correlations with the other instruments were comparable for all three forms. The random order of items within each set appears to break up a response set to endorse either the first or last item and is, therefore, recommended.

Adjustment Disorders↗

A chromosome 19 clone from a translocation breakpoint shows close linkage and linkage disequilibrium with myotonic dystrophy.

The gene for myotonic dystrophy (DM), the most common form of adult muscular dystrophy, is situated on the proximal long arm of chromosome 19. Although there exist markers that are tightly linked to the DM locus, its precise location is unknown. The identification and characterization of additional DNA probes closely linked to the DM locus continue to be priorities. In this study, we report on the linkage between a new DNA marker, designated p alpha 1.4P, and the DM locus in 50 families. The probe p alpha 1.4P was derived from a cloned breakpoint junction fragment from the chromosomal translocation t(14;19)(q32;q13.1). This translocation has been previously described in some cases of chronic lymphocytic leukemia. We have identified a BanI restriction fragment length polymorphism that is detected by p alpha 1.4P. Segregation analysis between this RFLP and DM revealed close linkage between the two loci (lod = 10.95, theta = 0). Furthermore, statistical evidence for linkage disequilibrium between p alpha 1.4P and the DM locus in a French Canadian population was found. Finally, by means of a somatic cell hybrid mapping panel, p alpha 1.4P was sublocalized to 19q12----19q13.2.

Alleles↗

Dopamine uptake blockers protect against the dopamine depleting effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse striatum.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a recently described neurotoxin, produces a marked dopamine (DA) depletion in the mouse striatum. In this study, a series of DA uptake blockers was tested for their ability to prevent this effect of MPTP. The agents tested (amfonelic acid, benztropine, bupropion and mazindol) completely protected against DA depletion in the mouse striatum when given before DA-depleting doses of MPTP were administered, whereas atropine and trihexyphenidyl (which were employed for comparative purposes) did not. DA uptake blocking agents appear to represent a second general class of compounds, monoamine oxidase inhibitors being the first, which protect against the biologic effects of MPTP in the mouse.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

A comparative clinical study of two pit and fissure sealants: 7-year results in Augusta, GA.

This 7-year evaluation of the Augusta study reinforces earlier conclusions regarding the long-term retention of sealants and their efficacy in caries protection. Although more time will be required to answer all the questions about sealants, sufficient data are now available to document their efficacy as caries-preventive agents. It is imperative that the dental profession provide this safe and effective preventive technique for the public so that dental disease can either be reduced or further postponed.

Bisphenol A-Glycidyl Methacrylate↗

A comparative study of two pit and fissure sealants: three-year results in Augusta, Ga.

A total of 254 children were examined 36 months after a single application of sealant. In 128 children, 201 permanent first molars were treated with Delton, and, in 126 children, 205 permanent first molars were treated with Nuva-Seal. Delton was completely retained on 80% of all paired permanent first molars, partially retained on 10%, and completely lost on 10% of the study teeth. Nuva-Seal was completely retained on 60% of all paired permanent molars, partially retained on 21%, and completely lost on 19% of the study teeth. Delton was 69% effective in preventing occlusal caries on permanent first molars three years after a single application. Nuva-Seal was 39% effective in preventing occlusal caries on permanent first molars three years after a single application. Both sealants have been shown to prevent dental caries on permanent first molars of children three years after a single application.

Child↗

Comparison of bubble and membrane oxygenators in short and long perfusions.

Eighty patients had cardiopulmonary bypass (CPB), half having short (109 +/- 11 minutes) perfusions and half having long (188 +/- 14 min) perfusions. Twenty patients in each group were perfused with bubble oxygenators (Bentley, Harvey, or Galen) and 20 with membrane oxygenators (Modulung or Teflo). Hemodilution to a hematocrit value of 22.5% +/- 1.4% and hypothermia to 28 degrees +/- 2 degrees C were used in all patients. Complete hemograms, sequential multiple analyzer 18 tests, coagulation profiles, blood gases and pH, three immunoglobulins, and two complement fraction proteins were sampled as follows: three times before perfusion, one to ten times during perfusion, 1 hour immediately after perfusion, and 4, 24, and 48 hours postoperatively. Data in concentration terms were compared statistically and reported as mean and standard error for each subset. Additionally, rates of gain or loss were calculated in terms of quantity per liter of blood pumped per minute. During perfusion for both duration sets, use of a membrane oxygenator resulted in greater pump flows (4.55 +/- 0.15 L/min versus 3.75 +/- 0.11 L/min), lower total peripheral resistances (1,125 +/- 63 dynes.sec.cm-5 versus 1,652 +/- 115 dynes.sec.cm-5), and greater urinary outputs (9.4 +/- 1.1 ml/min versus 2.2 +/- 0.6 ml/min) than in the bubble oxygenator subsets. Comparisons of measured and calculated data in the immediate postperfusion interval showed no differences between bubble and membrane oxygenator subsets for short perfusions. In long perfusions, the membrane subset had lower plasma hemoglobin and white cell concentrations and generation rates, smaller (3 to 8 1/2 times) losses of IgG, IgM, C3 and shed blood necessitating less transfusion, and greater C4 losses. The membrane oxygenator systems used were more complex and costly and offered no advantages for short perfusion in adults. In anticipated long perfusions or where bleeding may be a problem, a membrane oxygenator appears more efficacious than bubble systems. For perfusions of less than 2 hours, membrane oxygenators had no biochemical or hematologic advantage over the bubble devices used in this study.

Blood Cell Count↗