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Biomedical subjects

S J Berry

Publications and source records attributed to S J Berry.

At least 19 recordsLinked to original sources
PubMed1994

The requirement of the testis in establishing the sensitivity of the canine prostate to develop benign prostatic hyperplasia.

A long-term study on the requirement of the testis in establishing the sensitivity of the canine prostate to develop benign prostatic hyperplasia (BPH) was conducted using 23 aging beagles both with and without their testes. The dogs had received long-term restoration of testosterone and estrogen through silicone implants. When young beagles (0.5 to 1 year of age) were castrated and normal serum testosterone and estrogen levels restored during aging to 5 years, only 50% of these dogs developed BPH in the absence of their testes as opposed to 100% BPH development in intact controls. In addition, two-thirds of the prostates in the treated groups were remarkably reduced in size, being smaller than any prostate observed in the intact controls. If, following castration, the steroid restoration was withheld for 4 years during aging and subsequently administered starting at 5 years of age and continuing for a 6-month period, none of the animals developed complex BPH. Moreover, two-thirds of the prostate glands were reduced in size by more than 60% and were atrophied in spite of the maintenance of normal prostatic tissue dihydrotestosterone levels. Regardless of the time of steroid restoration to a castrate beagle, the periurethral zone of the canine prostate exhibits various degrees of atrophy indicating functional regions within the canine prostate that are sensitive to the requirements of the testes during aging. This study implicates the importance of the testis in increasing the probability and/or sensitivity for the full development of canine BPH.

Aging↗
PubMed1994

An actin infrastructure is associated with eukaryotic chromosomes: structural and functional significance.

The presence of actin in eukaryotic nuclei, and, especially, its functional significance has not been well established. We have found that under routine immunocytochemical conditions, no actin can be detected in insect follicle cell nuclei by means of antibody (both mono- and polyclonal) or phalloidin staining. However, a pretreatment of nuclear preparations with two different endonucleases (deoxyribonuclease I or micrococcal nuclease) to remove a substantial amount of chromosomal DNA uncovers the presence of nuclear actin for both antibody and phalloidin detection. Employing the same nuclease digestion followed by antibody or phalloidin staining with squash preparations of Drosophila polytene chromosomes revealed that the nuclear actin is directly associated with the chromosomes. A strong positive signal in the polytene chromosomes obtained with phalloidin labeling not only confirmed the presence of actin in the chromosomes, but indicates that a considerable amount of nuclear actin is present in filamentous form (F-actin) rather than monomeric (G-actin). The detection of actin associated with Xenopus embryo chromosomes suggests the significance of chromosomal actin for diploid vertebrate cells. Using the specific actin disrupting agent cytochalasin D, we have demonstrated the structural significance of nuclear actin in maintaining the linear integrity of polytene chromosomes. Further, we present evidence that RNA polymerase II closely interacts with the chromosomal actin scaffold, and that its association with chromosomes does not require the presence of DNA.

Actins↗
PubMed1992

A hybrid protein of urokinase growth-factor domain and plasminogen-activator inhibitor type 2 inhibits urokinase activity and binds to the urokinase receptor.

The binding of urokinase-type plasminogen activator (uPA) to its specific cell-surface receptor (uPAR) localises the proteolytic cascade initiated by uPA to the pericellular environment. Inhibition of uPA activity or prevention of uPA binding to uPAR might have a beneficial effect on disease states wherein this activity is deregulated, e.g. cancer and some inflammatory diseases. To this end, a bifunctional hybrid molecule consisting of the uPAR-binding growth-factor domain of uPA (amino acids 1-47; GFuPA) at the N-terminus of plasminogen-activator inhibitor type 2 (PAI-2) was produced in Saccharomyces cerevisiae. The purified protein inhibited uPA with kinetics similar to placental or recombinant PAI-2 and was also found to bind to U937 cells and to FL amnion cells. GFuPA-PAI-2 competed with uPA, the N-terminal fragment of uPA and a proteolytic fragment of uPA (amino acids 4-43) in cell binding experiments, indicating that the molecule bound to the cells via uPAR. Hence, both the uPA-inhibitory and uPAR-binding domains of the hybrid molecule were functional, demonstrating the feasibility of the novel concept of introducing an unrelated, functional domain onto a member of the serine-protease-inhibitor superfamily.

Amino Acid Sequence↗
PubMed1991

Purification and characterisation of plasminogen activator inhibitor 2 produced in Saccharomyces cerevisiae.

Expression of plasminogen activator inhibitor 2 (PAI-2) under the control of the protease B gene promoter in a mutant strain of Saccharomyces cerevisiae, DS569, resulted in its accumulation intracellularly at up to 20% of the soluble cell protein. Provision of an N-terminal signal sequence resulted in the secretion of a hyperglycosylated molecule. The intracellularly produced PAI-2 was purified by copper-chelate and anion-exchange chromatography to greater than 95% pure and was fully active. The recombinant PAI-2 formed SDS-stable complexes with urokinase and tissue-type plasminogen activator and inhibited the proteases with similar reaction kinetics to placental PAI-2 (second-order rate constant for uPA, 2.4 x 10(6) M-1 s-1, and for two-chain tPA, 0.7 x 10(5) M-1 s-1). As is the case for placental PAI-2, the N-terminus of the yeast-derived recombinant PAI-2 was blocked. The high productivity and consequent ease of purification mean that S. cerevisiae provides an excellent source of recombinant PAI-2 for investigation of its therapeutic potential in the treatment of neoplastic and inflammatory diseases.

Base Sequence↗
PubMed1991

Integrating the university medical center. Phase one: providing an information backbone.

UCLA School of Medicine represents a diverse computing community where the creation of each individual network has been driven by applications, price/performance and functionality. Indeed, the ability to connect to other computers has had no bearing on selection. Yet, there exists a need to seamlessly connect the individual networks to other minicomputers, mainframes and remote computers. We have created a school wide backbone network that will enable an individual from a single workstation to access a wide variety of services residing on any number of machines.

Academic Medical Centers↗
PubMed1990

Maternal messenger RNA distribution in silkmoth eggs. I. Clone Ec4B is associated with the cortical cytoskeleton.

We have constructed a cDNA library from mature egg RNA of the silkmoth, Hyalophora cecropia. Differential screening of the library using cDNA made against mRNAs from the yolky cytoplasm (soluble fraction) and the cortical cytoplasm (cytoskeletal-associated or cortical fraction) resulted in several clones that hybridized to a higher degree to the cDNA from the cytoskeletal-associated fraction. We selected and analyzed the clone giving the strongest signal (designated Ec4b) for its distribution in situ and found that it bound to mRNAs in the nurse cell cytoplasm, in the cortex and in the follicle cells of oocytes. Hybridization of the insert from Ec4b to both detergent-soluble and -insoluble (cortical) RNA on dot blots further supported the observation that the mRNA corresponding to Ec4b was enriched in this cytoskeletal fraction. The mRNA for Ec4b was approximately 500 bases long and the gene seems to be a member of a large multigene family in the H. cecropia genome. Analyses of the nucleotide and amino acid sequences reveal similarity to lepidopteran chorion genes and a lesser but convincing similarity to vertebrate cytokeratins. The filter and in situ hybridization data point to the association of specific messenger RNAs with the cortical cytoskeleton of silkmoth oocytes. Aspects of the structure of the protein encoded by this mRNA suggest that it is a structural component necessary for formation of the cellular blastoderm of the embryo. The association of this maternal mRNA with the cortical cytoskeleton presents the interesting possibility that mRNA bound to the cytoskeleton may be capable of participating in the synthesis of new cytoskeleton or related structures during blastoderm formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

Comparison of single-dose treatment with norfloxacin and standard 5-day treatment with trimethoprim-sulfamethoxazole for acute shigellosis in adults.

Shigellae have been shown to be highly susceptible to new quinolone agents, with average MICs for 90% of isolates of less than 0.1 microgram/ml. Because these agents also reach high concentrations in the stool after a single dose, the effectiveness of a single 800-mg dose of norfloxacin and of 5-day treatment with trimethoprim-sulfamethoxazole (TMP-SMX) were compared in a randomized trial. Patients with clinical dysentery received one of these treatment regimens, and clinical data and follow-up culture results were analyzed for patients whose stool culture on presentation grew shigellae. When 55 patients with shigellosis (26 treated with TMP-SMX, 29 treated with norfloxacin) whose bacterial isolates were susceptible to the antibiotic given were compared by treatment group, no significant differences were seen in days of illness (mean, 2.5 +/- 0.65 days with TMP-SMX and 2.0 +/- 0.47 days with norfloxacin; P = 0.200) or number of unformed stools after starting treatment (mean, 9.7 +/- 2.37 stools with TMP-SMX and 7.6 +/- 3.19 stools with norfloxacin; P = 0.312). Resistance in vitro to TMP-SMX was seen in 15% of Shigella isolates, whereas none was resistant to norfloxacin. Bacteriologic failure was found in 1 patient among 24 receiving TMP-SMX and in none of 25 patients receiving norfloxacin. One single dose of norfloxacin was as effective as 5 days of treatment with TMP-SMX in these adults with shigellosis.

Adult↗
PubMed1988

Cortical cytoskeleton of giant moth eggs.

Unfertilized eggs of several species of giant moths contain a substantial cortical cytoskeleton. This structure is assembled during oogenesis, and contains actin as a major fibrillar component. The presence of actin was confirmed by gel electrophoresis and binding to phalloidin, DNase I, and a monoclonal antibody against cytoskeletal actin. Several lines of evidence suggest that the fat body is a source of the actin in the oocyte and that the transport and acquisition of actin by the ovary are similar to the mechanism of vitellogenin acquisition. A possible role for the cortical cytoskeleton in directing early embryogenesis is discussed.

Actins↗
PubMed1987

DNA synthesis in the canine prostate: effects of androgen and estrogen treatment.

Canine prostatic DNA synthesis was evaluated by measuring [3H]thymidine incorporation into DNA of tissue slices in vitro. Among untreated beagles, prostatic DNA synthesis rates in young dogs with normal prostates, young dogs with spontaneous benign prostatic hyperplasia (BPH), and old dogs with BPH were 676 +/- 186, 1,220 +/- 156, and 641 +/- 88 cpm/100 micrograms DNA/hr, respectively. Among 81 young beagles (intact or castrated) that had been treated for 4 months with various steroids, rates of DNA synthesis varied according to the type of hormonal treatment. Prostatic DNA synthesis (cpm/100 micrograms DNA/hr) was significantly different (P less than 0.001) for dogs treated with estradiol alone (1,658 +/- 221 cpm/100 micrograms DNA/hr; n = 10 dogs), androgen alone (testosterone, 5 alpha-dihydrotestosterone, or 5 alpha-androstane-3 alpha,17 beta-diol; 1,000 +/- 61 cpm/100 micrograms DNA/hr; n = 31 dogs). However, there was no correlation between prostate size and rate of DNA synthesis (cpm/100 micrograms DNA/hr). Although treatment with estrogen alone resulted in the highest rate of DNA synthesis, it produced squamous metaplasia and the smallest prostates; these results are indicative of a high rate of cell turnover. Comparing prostates that reached the same size following 4 months of treatment with androgen alone or androgen plus estrogen, the rate of prostatic cell turnover was lower in the androgen plus estrogen group. These results are interpreted to indicate an inhibitory effect of estradiol on the rate of cell death in the presence of androgens.

Androgens↗
PubMed1987

Estrogen enhancement of androgen-induced renal growth in the male rat.

17 beta-estradiol enhances dihydrotestosterone-induced growth of the castrate male rat kidney by increasing cell number, cell size and tissue water retention. No estrogen enhancement was observed in sex accessory tissues or other organs. This estrogen enhancement of androgen-induced growth is discussed in relation to species and organ specificity.

Animals↗
PubMed1986

Effect of age, castration, and testosterone replacement on the development and restoration of canine benign prostatic hyperplasia.

An experiment was designed to test the effect of castration and testosterone replacement on the development of benign prostatic hyperplasia (BPH) in young and on the restoration of BPH in old beagles. Twenty beagles were divided by age into young (1.5-2.5-yr) and old (6.0-8.5-yr) groups. Each of these groups was further divided randomly into two additional groups of age-matched, intact, untreated control and castrate beagles. The latter were then treated with testosterone-filled Silastic implants designed to clamp serum testosterone at concentrations similar to those observed in adult beagles for 7 months beginning 5 months after castration. Histopathologic characterization of each prostate was completed on biopsy material obtained at the beginning and end of the experiment. Prostate weights were determined each month for 12 months via a noninvasive two-dimensional X-ray procedure. Testosterone treatment for 7 months allowed BPH to develop in young and restored BPH in old beagles. These results suggest that testosterone in the adult beagle acts permissively to allow BPH to develop in the prostate of the aging dog. Some other testicular product may be required for the continued growth of BPH in aged beagles.

Age Factors↗
PubMed1986

Development of canine benign prostatic hyperplasia with age.

The prevalence and growth of benign prostatic hyperplasia (BPH) in beagles as a function of age were studied. The normal prostate gland was 12 +/- 3 gm in beagles 2.1-3.0 years of age; this weight remained unchanged unless BPH developed. Histologic evidence of BPH developed at an early age with a prevalence of 16% of the dogs by the age 2 years. Fifty percent of the dogs had BPH, determined histopathologically by age 4.1-5.0 years. The average weight of the prostate gland remained constant until after age 8 years. With age, the pathologic features of BPH changed from glandular to the complex form, with no increase in prostate weight until after 8 years. Reinitiation of growth occurred and prostate weight increased to greater than 36 gm in eight of 185 beagles older than age 8 years.

Aging↗
PubMed1986

Effects of aging on prostate growth in beagles.

Statistical analysis of 82 variables was completed to determine the effects of aging in the male beagle on prostatic growth and function. The results indicate that prostate weight increased to 4 yr and then reached a plateau. Prostatic secretory function (measured as ejaculate volume) followed a course different than the growth of the gland. Prostatic function increased and reached a peak at 4 yr and then declined abruptly. Therefore, there is a separation of the growth and secretory function of the canine prostate after 4 yr of age. Multiple linear regression analysis was performed to determine the mathematical relationship of these variables in predicting prostate weight and therefore benign prostatic hyperplasia, which is correlated with weight. The testicular secretion of testosterone and aging were paramount factors in predicting prostate weight. There appears to be an increased sensitivity of the prostate to testosterone secretion with advancing age.

Aging↗
PubMed1985

Methods for monitoring canine prostate size: internal and external caliper measurements.

A method has been developed that allows the generation of a three-dimensional representation of the canine prostate from a pair of orthogonal radiographs. This information can be used to externally measure the length, width, and height of the prostate and from these results to calculate prostate weight. This externally estimated prostate weight is correlated closely (r = 0.90) with the actual prostate weight. The ability to generate an external caliper measurement of prostate weight will facilitate future studies of the effect of aging and hormonal manipulation on the canine prostate.

Aging↗
PubMed1984

Nuclear roundness factor. A predictor of progression in untreated Stage A2 prostate cancer.

A measurement of nuclear roundness involving computer-assisted image analysis of histologic specimens was used to predict the prognosis of 19 patients with Stage A2 prostate cancer. This technique accurately identified those tumors that clinically progressed without treatment and those that did not, in contrast to the Gleason grading system, which produced significant prognostic overlap. What separated most of these tumors was the quantification and degree of irregularity of a relatively small subpopulation of cancer nuclei among a majority of rounder nuclei. There are currently several practical limitations in the use of this method, but with improvements in technique and in methods of obtaining tissue, computerized image analysis of nuclear shape may become a valuable tool for analyzing prostate cancer in a quantitative manner, thereby providing valuable information relative to the prognosis of the individual patient.

Adenocarcinoma↗
PubMed1984

The influence of epididymal agenesis on the development and maturation of the testis: experimental model and clinical correlations.

The August X Copenhagen (ACI) rat provides an excellent model to study the effect of congenital epididymal anomalies on testicular function. Despite epididymal absence, testicular maturation and function are unchanged until puberty. At puberty, with increased testicular fluid and spermatozoa output, involution of germinal epithelium occurs. This involution is similar to the changes seen with ligation of the efferent ductules of the epididymis. These findings suggest that in this mammalian model the testis functions normally until the pubertal period. At that time, because of proximal epididymal agenesis and failure to reabsorb testicular secretions, intratesticular hydrostatic pressure increases with rapid germinal epithelial atrophy. Clinical correlations are made in patients with epididymal abnormalities, especially in association with undescended testis.

Animals↗