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L Birch

Publications and source records attributed to L Birch.

At least 37 records · Page 2Linked to original sources

Neonatal estrogen exposure up-regulates estrogen receptor expression in the developing and adult rat prostate lobes.

Neonatal exposure to estrogens results in permanent imprints of the rat prostate gland. To delineate the direct target of estrogen action within that tissue, the present study examined estrogen receptor (ER) expression by immunocytochemistry and in situ hybridization. ER were confined to mesenchymal cells in the urogenital sinus and proximal regions of the budding prostate lobes of newborn control rat prostates, and this expression declined after morphogenesis. Exposure to estradiol benzoate on days 1, 3, and 5 resulted in induction of ER expression in periductal smooth muscle cells from the proximal regions out to the distal tips of the developing prostate lobes. This ER expression was associated with the appearance of ER messenger RNA in those cells; thus, it was concluded that the up-regulation of ER by estrogens is mediated at the message level. Autoregulation of ER expression was next examined in adult prostates that had been exposed to oil or estrogens neonatally. Day 70 rats were castrated and given testosterone with or without estradiol for 7 days before death. Estrogen exposure in adulthood induced low levels of epithelial cell ER in the lateral lobe. Neonatal estrogenization increased the sensitivity of lateral lobe epithelial cells to this autoregulation, as the incidence and intensity of ER immunostaining were markedly increased. No autoinduction of ER was observed in adult ventral or dorsal prostatic lobes. From the present study we conclude that smooth muscle cells are the targets of estrogen action in the developmentally estrogenized prostate and that estrogen amplifies its own effects through auto-up-regulation of ER. In addition, lateral lobe epithelial cells are sensitive to estrogen up-regulation of ER, which may in part account for the lobe-specific effects observed after neonatal estrogenization of the prostate gland.

Animals↗

A rapid method for the determination of metal toxicity to the biodegradation of water insoluble polymers.

A rapid and inexpensive test has been developed to investigate the influence of elevated heavy metal concentrations on the degradation of biodegradable plastics. Using an overlay agar technique it could be demonstrated that copper concentrations above 8 to 14 mg/L inhibit the degradation of powdered poly(3-hydroxybutyrate), (PHB), by Acidovorax delafieldii. This is the first study demonstrating the inhibiting influence of metals on the biodegradation of PHB.

Journal Article↗

Location and concentration of estrogen, progesterone, and androgen receptors in the bladder and urethra of the rabbit.

The objective of this study was to determine location and concentration of estrogen, androgen, and progesterone receptors in the bladder and urethra of the rabbit. Two urethral and two bladder specimens were obtained from four 12-week-old female New Zealand white rabbits. Rat monoclonal antibody (AN1-15) to human androgen receptor and (H222) to human estrogen receptor and mouse monoclonal antibody (PR6) to chicken progesterone receptor were used. Immunocytochemical staining was performed and specimens were evaluated for presence and location of steroid receptors. Androgen receptors were found in the highest concentrations in urethral and bladder epithelium. Low to low/moderate concentration were found in smooth muscle. Estrogen receptors were found in moderate to moderate/high concentrations in urethral epithelium and bladder and urethral smooth muscle. Progesterone receptors were not found in appreciable concentrations from any location, though the animals were not pretreated with estrogen. The rabbit model suggests a mechanism by which estrogen therapy can be effective in treating postmenopausal lower urinary tract symptoms. Progesterone receptors were not found in appreciable concentrations, suggesting progesterone therapy may not diminish the effectiveness of estrogen therapy by acting on urethral progesterone receptors. The effect of androgens on the lower urinary tract needs further investigation to determine if androgen therapy can alleviate lower urinary tract symptoms.

Animals↗

The developmental pattern of androgen receptor expression in rat prostate lobes is altered after neonatal exposure to estrogen.

Brief administration of estrogen to newborn rats permanently imprints adult prostatic androgen receptor (AR) expression in a lobe-specific manner. To delineate this effect, we examined the immediate effects of early estrogen exposure on the changing AR pattern in the developing ventral, dorsal, and lateral prostate lobes. Antibodies against rat AR (PG-21) were used in combination with several antibodies to cell-specific antigens for positive cellular identification by immunocytochemistry. At birth, mesenchymal cells of the ventral prostate were strongly AR positive (AR+). Epithelial cells stained only for basal cell cytokeratins and, in contrast to earlier reports, many were AR+ on day 1. Between days 3-5, periductal mesenchymal cells differentiated into smooth muscle cells which retained strong AR+ staining, whereas interductal fibroblasts exhibited a decreased incidence of AR+ cells. Between days 5-10, luminal epithelial cells first appeared, and a striking increase in AR staining intensity was noted relative to that in the basal cells. During puberty, basal cells lost their AR immunoreactivity. Similar changes were observed in the dorsal and lateral lobes. Newborn rats were given 25 micrograms estradiol benzoate on days 1, 3, and 5 and were killed thereafter. By day 6, AR staining was markedly decreased to a weak to moderate intensity in all cell types, and by day 10, AR was virtually absent in the separate lobes. Growth and epithelial cytodifferentiation were significantly retarded. Between days 15-30, evidence of luminal cell cytodifferentiation was noted; however, this was frequently not associated with an increase in AR staining. In the ventral and dorsal lobes, a continuous peripheral layer of AR-negative basal cells surrounded the ducts in the central and proximal regions, and this was associated with a permanent inability of luminal epithelial cells to express AR. Epithelial and smooth muscle AR expression was observed only in the distal tips. In contrast, AR expression rapidly returned in all regions of the lateral lobes, except the proximal ducts. We conclude that 1) basal epithelial cells express AR as early as day 1 of life and should be considered as possible direct targets of androgen action during prostate morphogenesis; 2) differentiation into luminal cells is associated with an increase, rather than an induction, of AR expression; and 3) periductal smooth muscle cells retain strong AR expression throughout development and should be considered primary targets for androgen-mediated morphogenesis. Neonatal estrogen initially down-regulates AR expression in all cells of three lobes, which may explain the overall growth retardation.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Immunocytochemical analysis of androgen receptor along the ducts of the separate rat prostate lobes after androgen withdrawal and replacement.

Autoregulation of androgen receptors (AR) in the rat prostate gland has previously been shown to be lobe specific. Saturation ligand-binding assays revealed that AR fell to very low levels in the ventral and dorsal prostate within 7 days after castration, whereas lateral lobe AR were present at intact levels at that time. To study this differential response further, we herein analyzed AR in the separate prostate lobes by indirect immunocytochemistry after castration and testosterone replacement to adult rats. The ventral and dorsal lobes each contain one type of duct, whereas the lateral lobe is composed of two ductal systems, which were separated as LP1 and LP2. Frozen ducts were sectioned longitudinally to reveal the proximal-distal orientation. Sections were stained for AR with PG-21 antibody against rat AR. Within 2 days after castration, ventral and dorsal lobe immunoreactive nuclear AR was markedly decreased in staining intensity in the secretory epithelium compared to that in the intact rat and was absent in all stromal cells. Epithelial immunostaining continued to decline to a weak punctate nuclear signal by day 7, which further dissipated by day 21. Proximal and intermediate regions of the ducts were largely devoid of AR signal after castration, whereas residual nuclear staining was most apparent in epithelial cells of the distal ductal region. By day 7 and beyond, specific cytoplasmic staining for AR was also observed in distal tip epithelial cells. In the lateral lobe, LP1 ducts rapidly lost all AR immunostaining upon androgen withdrawal. In marked contrast, epithelial cells in the LP2 ducts retained AR immunostaining at all time points after androgen withdrawal at a signal intensity equivalent to that in the intact animal. Within 15 min after testosterone injection to 14-day castrate rats, considerable nuclear AR immunostaining was apparent within the distal tip epithelial cells of the ventral, dorsal, and lateral LP1 lobes. Cytoplasmic signal was noticeably reduced at this time. With increasing time after continued testosterone replacement, nuclear AR signal intensity increased, so that by 72 h, nuclear AR signal in all secretory epithelial cells approached the staining intensity observed in intact rats. AR immunostaining returned to smooth muscle and fibroblastic stromal cells within 1-3 days after testosterone replacement. In summary, immunodetectable AR declined in the ventral, dorsal, and LP1 prostate ducts after castration-induced androgen withdrawal and returned upon testosterone replacement, which further indicates that androgen up-regulates AR protein within these prostatic regions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of neonatal estrogen exposure on prostatic secretory genes and their correlation with androgen receptor expression in the separate prostate lobes of the adult rat.

Brief administration of estrogen to newborn rats permanently restricts prostatic growth and testosterone sensitivity in adulthood. Previous work demonstrated that neonatal exposure to estradiol benzoate produced lobe-specific imprints in prostatic androgen receptor (AR) expression. Epithelial cell AR was markedly reduced or absent in the adult ventral and dorsal lobes, which correlated with a lack of epithelial differentiation and responsiveness. While the lateral lobe also showed reduced growth and testosterone responsiveness after neonatal estradiol benzoate, normal cell differentiation and AR levels were observed within the adult epithelium. To determine the impact that these receptor imprints have on the functional capacity of adult tissue, we herein examined the expression of lobe-specific, androgen-dependent, or androgen-responsive secretory genes in prostates of rats given neonatal estradiol benzoate and directly compared this with epithelial cell AR using histological techniques. Sprague-Dawley rat pups were given 25 micrograms estradiol benzoate or oil on days 1, 3, and 5 and killed on day 90. Prostatic mRNA was analyzed using Northern blots and in situ hybridization. Ventral lobe mRNA was hybridized with a prostate binding protein (PBP) cDNA probe, while lateral and dorsal mRNA were hybridized with RWB (seminal vesicle secretory protein or SVS-II), probasin, and DP1 cDNA probes. Sections adjacent to those used for in situ hybridization were stained for AR by immunocytochemistry. Neonatal estradiol benzoate significantly reduced ventral lobe PBP message on Northern blots, and this was not restored with adult testosterone administration. There was a direct correlation between epithelial cell AR and PBP expression, in that PBP message and protein were only present in epithelial AR-positive cells and were absent in all AR-negative epithelium. In the lateral prostate, probasin expression was unaffected by neonatal estradiol benzoate, whereas RWB was slightly reduced using Northern analysis. By in situ hybridization, these messages were observed at normal levels in lateral lobe epithelial cells of estrogenized rats, which directly correlated with the presence of AR in those cells. In the dorsal prostate, different response patterns to neonatal estradiol benzoate were found for the three secretory genes analyzed. On Northern blots, DP1 message significantly declined, probasin mRNA was modestly suppressed, and RWB expression was significantly elevated compared to those in control tissue. In situ hybridization revealed that RWB expression in estrogenized dorsal lobes was amplified in AR-positive epithelial cells, whereas AR-negative cells appeared unaltered. In summary, prostatic functional activity after neonatal estradiol benzoate exposure is affected in a lobe-specific manner, which correlates with the AR imprints in the separate lobes.

Aging↗

Androgen receptor expression and 5 alpha-reductase activity along the proximal-distal axis of the rat prostatic duct.

The rat prostate consists of a series of branched ducts that eminate from the urethra. Heterogeneity of rat prostatic growth, secretory activity, and cell turnover has been observed along the proximal-distal axis of the branched ductal network. In addition, there are regional differences in androgen sensitivity along the ducts, with the distal ductal tips being highly androgen dependent and the proximal regions being relatively androgen independent. To determine the underlying mechanisms that may regulate these regional differences in androgen responsiveness, androgen receptor (AR) levels and 5 alpha-reductase activity were examined along the proximal-distal axis of microdissected ventral prostatic ducts from 15-, 30-, and 100-day-old rats. As in the murine prostate, DNA synthetic activity was concentrated in the distal tip region of the 15- and 30-day ducts. Immunocytochemistry and autoradiography with [3H] dihydrotestosterone were used to examine AR expression and functional ability to bind ligand, respectively. The results revealed no discernable differences in AR levels or binding activity in any cell type along the ductal length in prepubertal, pubertal, or adult rats. In addition, 5 alpha-reductase activity was the same in the distal and proximal ductal regions. We conclude that regional heterogeneity in prostatic growth and function is not a result of differences in levels of AR and 5 alpha-reductase. Rather, other region-specific structural, intracellular, or paracrine factors may be responsible for the differences in androgen responsiveness along the prostatic duct.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Growth response and androgen receptor expression in seminal vesicles from aging transgenic mice expressing human or bovine growth hormone genes.

Previous work has shown that expression of human (h) GH in transgenic mice is associated with significant age-related enlargement of seminal vesicles. To further explore this aberrant growth activity, we have characterized seminal vesicles from various GH transgenic lines and examined their androgen receptor (AR) content and distribution. Six groups of animals were initially studied: young adult (3-5 months) control mice, old (greater than 12 months) control mice, young adult hGH transgenic mice, old hGH transgenics, young adult bovine (b) GH transgenics, and old bGH transgenic mice. Young transgenic mice (hGH and bGH) possessed seminal vesicles with similar relative weights, DNA and protein contents, and AR levels as nontransgenic littermates. Histologically, the glands appeared similar. With aging, the hGH transgenic seminal vesicles exhibited massive stromal hyperplasia, whereas the glands from controls and bGH transgenic mice did not show this response. Seminal vesicles from old hGH mice presented with a marked increase in cell number (DNA content) and a marked decrease in cell size and/or glandular secretions (protein/DNA ratio) compared to those from old controls and young hGH transgenic mice. Tissue AR content was markedly reduced in old hyperplastic hGH seminal vesicles compared to that in seminal vesicles from young hGH transgenics, old controls, and old bGH transgenic mice. Immunohistochemistry indicated the absence of AR in the proliferating stromal cells, whereas acinar epithelial cells showed similar or moderately reduced AR staining intensity compared to control seminal vesicles. To examine whether the above results may be due to insertional mutagenesis rather than hGH itself, two additional GH transgenic lines were examined. Aged transgenic mice expressing bGH with an alternate promoter possessed seminal vesicle weights that were not different from those of old controls, whereas aged transgenic mice expressing an hGH. V gene (variant gene, placental origin) possessed significantly larger vesicles than the controls, which further suggests that vesicular hyperplasia is specifically related to hGH. To assess androgen responsiveness, aged control and hGH transgenic mice were castrated and examined after 15 days. While control seminal vesicles significantly decreased in size, glands from transgenic mice did not. Regressive changes were observed in the remaining epithelium of hGH transgenic mice; however, stromal tissue exhibited no response to androgen withdrawal. The present results suggest that the aging-associated seminal vesicle hyperplasia in hGH transgenic mice is a result of a massive increase in stromal tissue that is low or devoid of AR, suggesting a loss of direct androgen regulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Androgen receptor localization in different cell types of the adult rat prostate.

To better understand direct and indirect androgen action on rat prostatic growth and function, the various cell populations within the intact adult ventral, dorsal, and lateral prostate lobes were characterized for the presence or absence of androgen receptor (AR). Polyclonal rabbit antibodies raised against amino acids 1-21 of the rat AR (PG-21) were used in combination with a library of monoclonal antibodies directed against cell-specific antigens for positive cellular identification. Luminal epithelial cells were strongly AR positive, with an order of ventral greater than lateral greater than or equal to dorsal. In the lateral lobe, staining intensity was strongest in the peripheral regions, whereas a similar gradient was not apparent in the ventral and dorsal prostate. Basal epithelial cells were AR negative in all regions of the three lobes. Periacinar smooth muscle was strongly positive for AR, and this staining did not vary with the thickness of the muscle layer. Endothelial cells of the vasculature were AR negative, while the perivascular smooth muscle cells were AR positive. The majority of stromal fibroblasts were AR negative, although a number of AR-positive fibroblastic-appearing cells were observed within the ventral and dorsal lobes. Staining with ED2, a specific marker for tissue macrophages, revealed that fixed macrophages were present in significant quantities in the stroma of intact rat prostate lobes. Since these were frequently identified as AR positive, macrophages may partially account for the appearance of AR-positive stromal cells. Thus, the present findings indicate a complex pattern of AR expression among different cell types of the three prostate lobes. Cells types that express AR can potentially be considered as direct targets of androgen action, whereas those lacking AR should be considered as indirect targets or androgen-insensitive cells.

Animals↗

Prospective epidemiological study of common colds and secretory otitis media.

To evaluate how often a common cold induces secretory otitis media (SOM) two groups of young children were studied. One comprised 373 children aged 9 months to 7 years who were being minded in institutions. The other group consisted of 210 children not minded in day institutions or private day care. This latter group was subdivided into children minded at home or in private day care attended by not more than 2 children (117 children), and the remainder (93 children). Common colds were defined as nasal discharge, and tympanometry was carried out 6 times at 2-week intervals. Among the 1-year-olds common colds induced SOM in 83% of those minded in institutions and in 56% of those minded at home. At the age of 5 years this applied to 20% of both groups.

Child↗

A prospective epidemiological study of secretory otitis media in young children related to the indoor environment.

To assess the influence of housing upon the middle ear status in young children in the form of secretory otitis media (SOM), 210 children not looked after in kindergarten or municipal day-care were investigated. Tympanometry was performed 6 times at 2-week intervals, and the parents filled in a questionnaire concerning housing conditions. In addition to the number of times the children had suffered from SOM, we evaluated long-lasting cases, and the frequency of common colds. Age affected all 3 parameters and sex 1, the boys having a larger number of long-lasting episodes. As to housing factors, the type of housing was of importance, children living in flats being most apt to get SOM, and children on farms least, but this difference disappeared after a regression analysis. Both major and minor airing resulted in fewer cases of SOM than did average airing. Children with a history of allergy (but not of allergic rhinitis) caught colds more often than others.

Acoustic Impedance Tests↗

Prospective epidemiological study of secretory otitis media in children not attending kindergarten. An incidence study.

To assess the incidence of secretory otitis media in children minded at home we examined 210 children not attending kindergarten or municipal day care. Of these children 117 were minded exclusively at home or in private day care with up to 2 children. Tympanometry was carried out 6 times at 2-week intervals. Secretory otitis media (SOM) of more than 3 months' duration was found in 17% of the one-year-olds and in 6% of the total series. In the age range 1-5 years the incidence was from 0.35 to 0.19/child/month, and the mean for the total group was 0.26/child/month.

Acoustic Impedance Tests↗

Prospective epidemiological study of secretory otitis media in children not attending kindergarten. A prevalence study.

This prevalence study of secretory otitis media (SOM) comprised 210 children who were not attending or had not attended kindergarten. Children in home care/private day care with up to two children were analyzed separately. In this group the prevalence peak was at one year, being at that age about 40%. The prevalence decreased from the age 1-2 years, but thereafter it was steady at about 15-20%. The rest of the children showed another at the age of 4-5 years. Bilateral SOM was most common at the age of one year, but also showed another peak at 5 years of age. [corrected]

Acoustic Impedance Tests↗

Hearing improvement after stapedectomy: up to 19 years' follow-up period.

The long-term results of 925 stapedectomies were analysed after a mean follow-up period of 15 years. Patients who had the operation before the age of 30 were analysed separately. The entire group deteriorated by an average of 0.91 dB/year at 500-2000 Hz, while the under-30 group deteriorated by 0.67 dB/year. There were but slight differences in the conductive component, considering frequencies and age. The perceptive loss/year was not far from that in a normal population.

Adolescent↗

Impedance audiometric study of children. Comparison of impedance tympanoscope ZS 330 with impedance audiometer ZO 73 A.

In order to compare the impedance audiometer ZO 73 A with the impedance tympanoscope ZS 330 (both from Madsen Electronics), we examined 50 children who had been admitted to the ENT Department and 24 children from a kindergarten. There proved to be a good correlation between the middle ear pressure, except that ZO 330 showed a rather lower middle ear pressure. As regards compliance too there was a good correlation. The ipsilateral stapedial reflex was rather labile, and in 68% of the ears the two instruments showed conformity, while in 15% only ZO 73 A and in 17% only ZS 330 could elicit the reflex. When the middle ear pressure was lower than -100 mmH2O, the ipsilateral stapedial reflex could be elicited in only 25% of the cases, even though the middle ear pressure was equalized.

Acoustic Impedance Tests↗

Daily impedance audiometric screening of children in a day-care institution.

Fifty-seven children in a fairly new day-care institution were examined daily by impedance audiometry for 4 weeks. A Madsen Electronics ZS 330 tympanoscope was used. The tympanometric curves were divided into types A, C1, C2, and B. Completely flat curves and cases in which the compliance was less than 0.25 ml, combined with an absent ipsilateral stapedial reflex, were also interpreted as type B. The object was to ascertain how quickly the types changed and how stable the B curves were. A total of 43 episodes of B curves occurred. Of them, 16 lasted for only 1 day and thereafter 9 became quite flat. Only a few lasted for 8-23 days and 8 continued for 26 days or longer.

Acoustic Impedance Tests↗

Stapedectomy and vertigo.

The relationship between vestibular and cochlear function in stapedectomy was investigated in 722 patients (925 ears). There were no differences in hearing between patients with and without pre-operative complaints of vertigo. Post-operatively patients with long lasting vertigo obtained equally good hearing results as the others. The direction of spontaneous nystagmus post-operatively in relation to the operated ear was of no prognostic significance regarding short term hearing results. However, at follow-up an average of 15 years after the operation, hearing was somewhat poorer in those having spontaneous nystagmus towards the operated ear. At follow-up 17% had an abnormal caloric test.

Caloric Tests↗