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J A Gosling

Publications and source records attributed to J A Gosling.

At least 19 recordsLinked to original sources

Co-localization of nitric oxide synthase, neuropeptides and tyrosine hydroxylase in nerves supplying the human post-natal vas deferens and seminal vesicle.

OBJECTIVE: To determine the distribution and patterns of co-localization of nitric oxide synthase (NOS), neuropeptides and tyrosine hydroxylase (TH) in intrinsic nerves of the human post-natal vas deferens and seminal vesicle. MATERIALS AND METHODS: Double and triple immunolabelling methods were used in tissue from 10 male infants and children (age range 2 months to 3 years) obtained at post-mortem examinations carried out within 12 h of death. RESULTS: Most nerves supplying the muscle coat of either organ were TH-immunoreactive (-IR), most of which also contained neuropeptide Y (NPY) while a smaller proportion contained both NPY and NOS. Minor populations of the TH/NPY-IR intramuscular nerves contained calcitonin gene-related peptide (CGRP), galanin (GAL), met-enkephalin (m-ENK) or vasoactive intestinal polypeptide (VIP). Non-TH-IR intramuscular nerves were relatively infrequent and most contained NPY and either VIP or NOS. Presumptive secretomotor nerves formed subepithelial plexuses in both organs, most of which contained NPY co-localized with either VIP or NOS, with minor populations containing CGRP and/or GAL. TH- and substance P (SP) -IR nerves were not observed subepithelially. Perivascular nerve plexuses were mainly formed by TH-IR varicose nerves, most of which contained co-localized NPY and CGRP, with a smaller proportion containing NPY and NOS and minor populations containing VIP, m-ENK, SP or GAL. CONCLUSION: These results indicate that the autonomic control of the human vas deferens and seminal vesicle is provided by several immunohistochemically distinct nerve populations. Furthermore, NOS is present in a proportion of both the noradrenergic and non-noradrenergic nerves. Pharmacological studies are now required to elucidate the precise roles of nitric oxide and neuropeptides in the functional control of these organs.

Biomarkers

A double-label immunohistochemical study of intramural ganglia from the human male urinary bladder neck.

Double-label immunocytochemistry was used to investigate the colocalisation of various neuropeptides and the enzymes nitric oxide synthase (NOS) and tyrosine hydroxylase (TH) in intramural ganglia of the human male urinary bladder neck and trigone. Postmortem specimens were obtained from 7 male infants and children ranging in age from 2 mo to 3 y who had died as a result of cot death or accidental trauma. On average 60% of the intramural neurons were non-TH-immunoreactive (-IR) (i.e. presumptive cholinergic) and 40% were TH- and D beta H-IR (i.e. noradrenergic). Within the non-TH-IR population, calcitonin gene-related peptide (CGRP) was found in 65% of cells, neuropeptide Y (NPY) in 90%, nitric oxide synthase (NOS) in 45%, somatostatin (SOM) in 90%, and vasoactive intestinal polypeptide (VIP) in 40%. The corresponding values for the TH-IR neurons were CGRP (54%), NPY (70%), NOS (58%), SOM (73%) and VIP (40%). All the observed bombesin (BOM)-immunoreactivity was colocalised with TH while 90% of VIP and almost all the CGRP was colocalised with NPY. Less than 5% of neurons were immunoreactive for substance P (SP) or met-enkephalin (m-ENK) and some of these also contained TH. Varicose nerve fibres were seen in close proximity to some of the intramural neurons, the majority of such varicosities showing immunoreactivity to CGRP, VIP or TH. Less common were pericellular varicosities immunoreactive to NPY, SOM or SP. These results demonstrate the neurochemical heterogeneity of intramural neurons in the human bladder neck and provide indirect evidence for the complexity of the peripheral innervation of the human urinary bladder.

Calcitonin Gene-Related Peptide

Modification of bladder structure in response to outflow obstruction and ageing.

The morphology of the normal bladder has been compared with that of the obstructed and the ageing bladder, using both light and electron microscopy. In the normal bladder the smooth muscle cells are closely packed together with relatively little intervening connective tissue. The smooth muscle bundles are innervated predominantly by autonomic presumptive cholinergic nerve fibres, while adrenergic nerves are usually observed in association with blood vessels. In the obstructed bladder, many smooth muscle cells are surrounded by large amounts of connective tissue and some of the muscle cells change their function from contracting to seemingly being involved in collagen synthesis. A significant reduction in the innervation of the smooth muscle cells is observed. In the ageing bladder, the smooth muscle cells have a normal morphology which is in contrast to the findings in the obstructed bladder. A reduction in the innervation of the ageing bladder is observed, although to a considerably lesser extent than that observed in the obstructed bladder. As the morphology of the obstructed bladder differs from that of the ageing bladder, it is unlikely that the changes seen in the obstructed bladder simply reflect a function of age.

Adult

Co-localisation of tyrosine hydroxylase, nitric oxide synthase and neuropeptides in neurons of the human postnatal male pelvic ganglia.

Double-label immunocytochemistry was used to investigate the co-localisation of neuropeptides and the enzyme nitric oxide synthase (NOS) with tyrosine hydroxylase (TH) in autonomic ganglia of the human postnatal male pelvic plexus. Postmortem specimens were obtained from six male infants and children ranging in age from 2 to 12 months who had died as a result of cot death or accidental trauma. On average, ganglia lying adjacent to the neck of the urinary bladder contained 45% of neurons which were TH-immunoreactive (-IR) while ganglia situated adjacent to the posterior and lateral aspects of the prostate gland contained 67% of neurons which were TH-IR. All the TH-IR neurons also contained dopamine beta-hydroxylase and were considered to be noradrenergic in type. On average, 61% of TH-IR neurons in bladder ganglia contained NOS, compared with 77% of non-TH-IR neurons (based on counts of over 1,000 cells in each case), while the percentages of TH- and non-TH-IR neurons containing neuropeptides were: calcitonin gene-related peptide (CGRP) (30%; 11%), neuropeptide Y (NPY) (66%; 92%), somatostatin (SOM) (70%; 29%), substance P (SP) (64%; 46%), vasoactive intestinal polypeptide (VIP) (64%; 83%). The equivalent values for TH- and non-TH-IR neurons in prostatic ganglia were NOS (38%; 59%), CGRP (55%; 18%), NPY (62%, 65%), SOM (14%, 20%), SP (13%, 8%) and VIP (42%; 82%). Varicose nerve fibers within the ganglia were seen forming pericellular arborizations around many of the ganglion cells, the most numerous containing TH-, CGRP-, NPY-, SOM- or VIP-immunoreactivity. Less common were pericellular varicosities containing SP-immunoreactivity while terminals containing NOS were not observed. No correlation could be detected between the peptide contents of the ganglion cells and of the associated pericellular terminals. However, the peptide content of the ganglion cells found in association with the urinary bladder and prostate gland correlates well with the previously documented coexistence of enzymes and neuropeptides in the intrinsic nerve fibers supplying these two regions of the human postnatal male genitourinary system.

Dopamine beta-Hydroxylase

Nitric oxide synthase and tyrosine hydroxylase are colocalized in nerves supplying the postnatal human male genitourinary organs.

PURPOSE: The objective of this study was to examine the distribution of nitric oxide synthase (NOS) and the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) in nerve fibers supplying the human neonatal male genitourinary organs. MATERIALS AND METHODS: An indirect double label immunofluorescence technique was employed on specimens obtained from infants and children at postmortem examination. RESULTS: Many nerve fibers immunoreactive for both NOS and TH were observed in the muscle coat of the vas deferens and the seminal vesicle, within the fibromuscular stroma of the prostate gland and at the bladder neck, and also formed perivascular plexuses in each of these organs. Double-labeled nerves occurred less frequently in the intramural ureters and superficial trigone while similar nerves in the bladder body were relatively sparse. Numerous nerves immunoreactive for NOS but not TH were observed at the base of the epithelium of each organ examined. Four types of autonomic ganglion cell were observed in nearby pelvic ganglia: those which contained NOS and TH, those which contained NOS alone, those which contained TH alone and those which contained neither NOS nor TH. CONCLUSION: The results indicate that many of the noradrenergic nerves as well as non-noradrenergic nerves supplying the male genitourinary organs have the capacity to synthesize nitric oxide (NO) and that NO may play a significant role in the autonomic control of both the urinary and genital organs in the postnatal human male.

Cadaver

A quantitative histological evaluation of the dilated ureter of childhood. II: Ectopia, posterior urethral valves and the prune belly syndrome.

A quantitative histological study was performed on specimens of 33 ureters obtained from 14 male and 19 female patients 5 days to 14 years old (mean age 1.2 years). A high resolution color image video analysis system was used to quantify and compare collagen and smooth muscle components of the muscularis layers to normal control ureters from patients of similar ages. In comparing ureters with ectopia (7), ureters with ectopic ureteroceles (20) and control ureters (4) there was not a statistically different collagen-to-smooth muscle ratio among the groups. In the patients with posterior urethral valves the amount of collagen and smooth muscle was not statistically different from controls (p > 0.01), although the collagen-to-smooth muscle ratio was increased. The 4 patients with the prune belly syndrome had a collagen-to-smooth muscle ratio that was markedly elevated (1.21 versus 0.39) compared with controls. When this group was analyzed as 2 separate groups (obstructed versus refluxing ureters) the difference was more apparent (p < 0.004). Ureters with ectopia or ectopic ureteroceles and ureters associated with posterior urethral valves had similar quantitative amounts of smooth muscle (60%, 56% and 52%, respectively). In patients with the prune belly syndrome obstructed ureters had 65% muscle and refluxing ureters had 38% muscle on evaluation. The percentage of collagen was 33% in ureters with ectopia, 37% in those with ureteroceles and 48% in those associated with posterior urethral valves compared with 23% in controls. In the group with the prune belly syndrome there was 30% collagen in obstructed ureters and 62% collagen in refluxing ureters. Our findings demonstrate that while these dilated ureters had different etiologies the overall quantitative composition of collagen-to-smooth muscle ratios was similar except in refluxing ureters associated with the prune belly syndrome. Our study provides further insight into the pathological nature of such ureters and considerations for surgical repair.

Adolescent

Immunohistochemical localization of neuromarkers and neuropeptides in human fetal and neonatal urinary bladder.

OBJECTIVE: To use immunohistochemical techniques to determine the spatial and temporal distribution of a variety of neuropeptides in the human fetal and neonatal urinary bladder. MATERIALS AND METHODS: Thirteen pre-natal specimens ranging in gestational age from 17 to 35 weeks were acquired following abortion or miscarriage. In addition two post-natal specimens aged 8 and 12 weeks were obtained at post-mortem and were included in this study. The overall innervation of each specimen was visualized using the general nerve marker protein gene product 9.5 (PGP). Localization of dopamine-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) revealed putative noradrenergic nerves. The neuropeptides studied included neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP). RESULTS: At 17 weeks a rich plexus of PGP and NPY-containing nerves was present throughout the detrusor muscle coat. As gestational age increased, VIP, SP and CGRP-containing nerves were observed with increasing frequency although SP and CGRP were mainly confined to perivascular nerve plexuses. TH- and DBH-containing nerves were first observed in the intramural ureters at 30 weeks and the detrusor muscle at 35 weeks and were relatively numerous in the intramural ureters and muscle of the superficial trigone in the two post-natal specimens. PGP-containing nerves were first observed beneath the bladder epithelium at 23 weeks and gradually became more numerous with increasing age. Occasional NPY, VIP, SP and CGRP-containing nerves were observed in the submucosa but TH- and DBH-immunostained nerves were especially numerous in the mucosa of the trigone in the two post-natal specimens, many such nerves being unrelated to the vascular supply. CONCLUSIONS: The bladder detrusor possesses a rich autonomic innervation by 17 weeks of gestation and this presumptive cholinergic innervation is associated with NPY immunoreactivity. Presumptive noradrenergic nerves appear relatively late in pre-natal development and mainly supply the intramural ureters and superficial trigone. A submucosal plexus of nerves has been demonstrated, the functional significance of which remains uncertain.

Calcitonin Gene-Related Peptide

Development of peptide-containing nerves in the human fetal vas deferens and seminal vesicle.

OBJECTIVE: To use immunohistochemical methods to study the developing autonomic innervation of the human fetal vas deferens and seminal vesicle. MATERIAL AND METHODS: Thirteen pre-natal specimens ranging in gestational age from 13 to 30 weeks were acquired following abortion or miscarriage. The overall innervation of each specimen was visualized using protein gene product 9.5 (PGP), a general nerve marker, while the onset and development of specific neuropeptide-containing sub-populations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene related peptide (CGRP), bombesin (BOM), somatostatin (SOM), and met-enkephalin (ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). RESULTS: At 13 weeks numerous PGP, D beta H, TH, NPY and ENK immunoreactive (-IR) nerve trunks were present in the adventitia of the vas deferens and seminal vesicle but at this stage nerve fibres were not present in the smooth muscle coat of either organ. By 17 weeks, fine PGP-, D beta H, and TH-IR nerve fibres had penetrated the outer aspect of the muscle coat of the seminal vesicle but not the vas deferens. At 20 weeks a branching network of PGP-, D beta H- and TH-IR nerve fibres occurred throughout the full thickness of the muscle coat of the seminal vesicle while similar nerves were present only in the outer half of the muscle coat of the vas deferens. At 23 weeks the full thickness of the muscle coat of the vas deferens was richly innervated by a branching plexus of PGP-IR nerves. Many of these adventitial and intramuscular nerves were immunoreactive for D beta H or TH while some were immunoreactive for either NPY or ENK. Occasional adventitial nerves were immunoreactive for SP or CGRP, these being first observed at 20 weeks. VIP-IR nerves were extremely rare in the muscle coat of either organ, being first observed at 17 weeks in the seminal vesicle and at 20 weeks in the vas deferens where they mainly formed perivascular plexuses. PGP-IR nerves were first observed in the submucosa of the seminal vesicle at 20 weeks and in the vas deferens at 21 weeks. Some of these nerves were perivascular in location while other formed a subepithelial plexus which increased in density with increasing gestational age. At 22 weeks of gestation some of the submucosal nerves were immunoreactive for SP or NPY, while at 30 weeks NPY-IR nerves formed the majority of subepithelial nerves. Occasional VIP-IR subepithelial nerves were first observed at 26 weeks but were extremely rare even at 30 weeks. Submucosal nerves immunoreactive for CGRP, D beta H, TH or ENK did not occur in any of the specimens examined. CONCLUSION: (i) From 13 weeks gestation autonomic nerves develop in the muscle coat of the fetal seminal vesicle and vas deferens, being denser in the seminal vesicle than the vas deferens up to 23 weeks gestation. (ii) The majority of the intramuscular nerves in either organ contain D beta H, TH, NPY and ENK and are presumably noradrenergic in type. (iii) A subepithelial nerve plexus develops around 20 weeks gestation and contains NPY but not VIP, unlike the adult organs. (iv) Scattered neuroendocrine cells immunoreactive for SOM are present in the mucosa of the seminal vesicle from 23 weeks of gestation.

Autonomic Nervous System

The innervation of the human myocardium at birth.

In order to delineate the type and distribution of autonomic nerves within the atrial and ventricular myocardium of the neonatal human heart, numerous samples of atrial and ventricular myocardium from 4 neonatal human hearts with no cardiac anomaly, freshly obtained at necropsy, were processed and studied using immunohistochemical and enzyme histochemical techniques. The antisera included those used to demonstrate protein gene product (PGP) 9.5 as a general neural marker, dopamine beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) as indicators for presumptive sympathetic neural tissue, and neuropeptide Y (NPY). A histochemical technique was used to reveal tissue cholinesterase activity. Numerous PGP-immunoreactive (PGP-IR) nerves were seen in the atrial myocardium, forming perivascular plexuses and lying in close apposition to myocardial cells. Fewer PGP-IR nerves were found amongst the myocardium of the ventricles. Both DBH-IR and TH-IR nerves demonstrated a similar pattern of distribution as that of PGP-IR nerves; in the atria, however, they were less numerous, while in the ventricles, their density approximated to that of PGP-IR nerves. Relatively few NPY-IR nerves were observed either in the atrial or the ventricular myocardium. The density of acetylcholinesterase (AChE) positive nerves in the walls of the atria was less than that of PGP-IR nerves although their distribution patterns were similar. In the ventricles, AChE positive nerves were rarely observed. It is concluded that the neonatal human heart possesses a rich supply of autonomic nerves. The atria possess at least two populations of nerves, presumably sympathetic and vagal, whereas the walls of the ventricles are innervated principally by presumptive sympathetic nerves.

Acetylcholinesterase

An immunohistochemical study of the innervation of the ureterovesical junction in infancy and childhood.

OBJECTIVE: To use histological and immunohistochemical methods to study the structure and innervation of the human ureterovesical junction (UVJ). MATERIALS AND METHODS: A series of 24 post-natal specimens taken from patients ranging in age from 1 month to 6 years were examined. Routine histological slides were stained with Masson's trichrome. In addition, an indirect immunohistochemical method was used to study the occurrence and distribution of nerves immunoreactive for the neuropeptides vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), substance P (SP) and calcitonin gene-related peptide (CGRP). Immunoreactivity to tyrosine hydroxylase (TH), dopamine-B-hydroxylase (DBH) and to protein gene product (PGP) 9.5, a general nerve marker, were also studied. RESULTS: The UVJ comprised a ureteric muscle component (the intramural ureter) and a detrusor component (the immediately adjacent region of the urinary bladder). In the majority of specimens a third or intermediate layer was also present. This additional component consisted of tightly-packed smooth muscle cells which formed an incomplete layer that partially surrounded the juxta-vesical and intramural parts of the ureter. Numerous PGP-, VIP-, NPY, DBH- and TH- like immunoreactive (-LIR) nerves were associated with the smooth muscle bundles which comprised the intramural ureter. Such nerves ran in the connective tissue separating ureteric smooth muscle bundles and rarely coursed amongst individual smooth muscle cell comprising each bundle. SP- and CGRP- containing nerves were rarely observed in association with the intramural ureter and none were detected in the ureteric submucosa. The intermediate muscle layer was richly innervated by PGP-, TH-, DBH- and NPY- containing nerves which ran amongst the smooth muscle cells comprising this layer. VIP-, SP- and CGRP-LIR nerves were not observed within the intermediate layer. The detrusor component of the UVJ was innervated by PGP-, NPY- and VIP-LIR nerves which frequently extended between the smooth muscle cells forming the detrusor muscle bundles. TH-, DBH-, SP- and CGRP-LIR nerve fibres were rarely encountered. CONCLUSION: These findings indicate that noradrenergic nerves play a major role in the control of the ureteric component of the UVJ. In addition, the present results form baseline morphological data with which to compare the results of future studies on the structure of the UVJ in cases of vesicoureteric reflux.

Child

The intramural innervation of the human vas deferens and seminal vesicle in infants and children.

Immunohistochemical methods were used to study the autonomic innervation of the vas deferens and seminal vesicle in a series of human postnatal specimens ranging in age from 1 month to 3 years. The occurrence and distribution of nerves immunoreactive for the neuropeptides vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) substance P (SP) and calcitonin gene-related peptide (CGRP) were investigated. In addition immunoreactivity to tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and to protein gene product (PGP 9.5), a general nerve marker were also studied. A neurohistochemical method was used to localise acetylcholinesterase. The results obtained from either organ were similar. Regardless of age, a rich plexus of nerve fibres immunoreactive for PGP 9.5 was present both within the muscle coat and also beneath the epithelium of the vas deferens and seminal vesicle. Some acetylcholinesterase containing nerves occurred in the muscle coat but the majority were found under the epithelium in the connective tissue of the mucosa. TH and DBH-containing nerves (presumably noradrenergic in type) formed dense intramuscular plexuses but none occurred subepithelially. In contrast NPY-containing nerves formed a less dense intramuscular plexus and were also observed beneath the epithelium. Thus while NPY may occur in some of the intramuscular noradrenergic nerve fibres it is clearly not confined to this type of nerve in either the vas deferens or the seminal vesicle. SP- and CGRP-containing nerves were extremely infrequent and, when observed, were confined to the muscle coat.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous System

Ultrastructural observations on cystitis cystica in human bladder urothelium.

Cystitis cystica, a common urothelial pathology whose aetiology, morphology and clinical significance are poorly understood, affects the human urinary bladder and trigone in both sexes. We have studied the fine structure of urothelial cysts in 11 patients diagnosed cystoscopically as suffering from cystitis cystica. Several abnormal features were observed in the adjacent urothelium, including large intracellular vacuoles (4 patients), Brunn's nest (5), lymphocyte infiltration (10) and generally disorganised urothelial architecture (10). Squamous metaplasia was observed in one case. The wall of each cyst consisted of a 2-3 layered epithelium with either tall columnar or flattened cells lining the fluid-filled lumen. Both types of lining cell possessed short microvilli, while the columnar type also contained numerous membrane-bound, electron dense secretory granules in the apical cytoplasm. Rough endoplasmic reticulum, mitochondria and Golgi membranes were plentiful in the surface cells. Junctional complexes joined adjacent lining cells. The deeper cells contained relatively fewer organelles, while a basal lamina separated the cyst wall from the underlying connective tissue.

Aged

Innervation of the human cardiac conduction system at birth.

OBJECTIVE: To study the pattern of innervation of the conduction system of the neonatal heart in humans. DESIGN: A prospective analysis based on immunohistochemical and enzyme histochemical examination of newborn human hearts. SETTING: A general district hospital. MAIN OUTCOME MEASURES: Fresh necropsy tissue. MATERIAL: Hearts of three neonatal humans with no cardiac anomaly, freshly taken at necropsy. METHODS: Serial sectioning to obtain a three dimensional reconstruction of the cardiac conduction system, followed by identification of the pattern of innervation by immunohistochemical and enzyme histochemical techniques; with a panel of antisera against protein gene product (PGP) 9.5 as a general neural indicator; dopamine beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) as indicators for sympathetic neural tissue; and selected neuropeptides--namely, neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP), and substance P (SP). Gomori's technique was used for locating cholinesterase activity. RESULTS: PGP immunoreactive (PGP-IR) nerves were present in large numbers in the sinus node, atrioventricular (AV) node, and penetrating atrioventricular bundle; in moderate numbers in the branching bundle; and occasionally in the bundle branches. Small numbers of DBH-IR and TH-IR nerves were seen in the sinus and AV nodes, mainly perivascularly; there were few in the penetrating and branching bundles and none in the bundle branches. A few perivascular NPY-IR nerves were seen only in the sinus node. VIP-IR, CGRP-IR, and SP-IR nerves were not seen. Pseudocholinesterase activity was found in the conduction tissue, whereas occasional acetylcholinesterase positive nerves were found only in the sinus and AV nodes. CONCLUSION: A considerable innervation of the human cardiac conduction system is present at birth, although, by comparison with the results of other studies on adult tissue, the mature pattern has not yet been established. Thus it is still in the process of maturation, especially with regard to the acquisition of various neurotransmitters, including the more recently described neuropeptides.

Calcitonin Gene-Related Peptide

A quantitative histological analysis of the dilated ureter of childhood.

A quantitative histological study of the dilated ureter of childhood was performed on 26 ureters. The specimens were from 15 male and 11 female patients 10 days to 12 years old (mean age 2.0 years). A color image analysis system was used to examine and compare collagen and smooth muscle components of the muscularis layers to normal control ureters of similar age. In comparing primary obstructed (12) to primary refluxing (14) megaureters and control ureters (6), there was a statistically different collagen-to-smooth muscle ratio (p < 0.001) between the primary obstructed and primary refluxing megaureter groups. For patients with primary refluxing megaureter there was a 2-fold increase in the tissue matrix ratio of collagen-to-smooth muscle when compared to patients with primary obstructed megaureter. In the primary obstructed megaureters the amount of collagen and smooth muscle was not statistically different from controls (p > 0.01). The increased tissue matrix ratio of 2.0 +/- 0.35 (collagen-to-smooth muscle) in the refluxing megaureter group compared to 0.78 +/- 0.22 in the obstructed megaureter group and 0.52 +/- 0.12 in controls was found to be due not only to a marked increase in collagen but also a significant decrease in the smooth muscle component of the tissue. Primary obstructed and normal control ureters had similar quantitative amounts of smooth muscle with 60 +/- 5% and 61 +/- 6%, respectively, while refluxing megaureters had only 40 +/- 5% smooth muscle. The percentage collagen was 36 +/- 5 in the obstructed megaureter group and 30 +/- 5 in controls, with refluxing megaureters having 58 +/- 5% collagen on analysis. Our findings emphasize the significant differences in the structural components (collagen and smooth muscle) of the dilated ureter of childhood, and provide us with further insight into the pathological nature of these dilated ureters and their surgical repair.

Child

An immunohistochemical study of human postnatal paraganglia associated with the urinary bladder.

Histological and immunohistochemical methods were used to study pelvic paraganglia in a series of human postnatal specimens ranging in age from 1 month to 6 y. Up to 5 months of age, many of the encapsulated paraganglia contained small pacinian-like sensory corpuscles which occurred either singly or in small clusters, implying an unknown functional interrelationship during this period. In older specimens, this intimate association was not observed since pacinian corpuscles and small nonencapsulated clusters of paraganglion cells were observed only as separate structures. It is suggested that the paraganglion cells may induce the formation of the pacinian corpuscles during fetal development. Immunohistochemistry using the nerve marker protein gene product (PGP 9.5) demonstrated a rich plexus of varicose nerve fibres within the paraganglia which may directly innervate the paraganglion cells and/or be associated with the profuse vascular supply. A similar density of vasoactive intestinal polypeptide-containing nerves was also demonstrated while some of the nerves contained calcitonin gene related peptide or substance P. The paraganglion cells stained positively for tyrosine hydroxylase, dopamine-beta-hydroxylase and neuropeptide Y, but not for phenylethanolamine N-methyltransferase. This combination of immunostaining confirms them as a rich source of noradrenaline.

Age Factors

Cystometric, physiological and morphological studies after relief of bladder outflow obstruction in the pig.

Experimental bladder outflow obstruction was relieved in 18 pigs between 2 and 15 months after the creation of partial urethral obstruction. Cystometric, physiological and morphological studies were performed 2 to 6 months after relief of the obstruction. An increase in average voiding flow rates from 2.8 +/- 1.0 ml/s to 6.8 +/- 1.2 ml/s was recorded in the Landrace pigs and from 2.2 +/- 0.9 ml/s to 7.4 +/- 1.4 ml/s in the Göttingen mini-pigs. There was a concomitant decrease in the voiding detrusor pressures from 52 +/- 11 cm H2O to 32 +/- 8 cm H2O and from 78 +/- 12 cm H2O to 33 +/- 6 cm H2O respectively. A return towards control values of the physiological responses to exogenously applied agonists (acetylcholine and potassium) and to electrical field stimulation was observed. There was an increase in neuronal innervation in the morphological studies which was more marked in the animals with a shorter period of obstruction. The implications for patient care are discussed.

Acetylcholine

The fine structure of Brunn's nests in human bladder urothelium.

The aetiology, morphology and clinical significance of Brunn's nests in human bladder urothelium are poorly understood. In the present study, 9% of a population of 100 consenting patients undergoing diagnostic or review cystoscopies were histologically found to have Brunn's nests, although their presence was not detected endoscopically. Of the nine cases, four were diagnosed with cystitis cystica, two with bladder papillomata, one with transitional cell carcinoma and cystitis cystica, and two were considered to be macroscopically normal. Mucosal biopsies were removed from areas unaffected by macroscopic abnormalities. Brunn's nests consisted of rounded collections of cells, whose nuclei contained prominent nucleoli and occasional nuclear bodies. The cytoplasm frequently contained clusters of mitochondria, together with Golgi membranes and cisternae of granular endoplasmic reticulum while small membrane bound vesicles containing electron dense material were present in some cells. Presumptive lysosomes were rarely observed. Thus Brunn's nest cells generally resembled normal urothelial cells in both their nuclear and cytoplasmic fine structure. Brunn's nests were surrounded by a basal lamina and loose connective tissue containing fenestrated capillaries.

Cell Nucleus

Studies on the structure and intrinsic innervation of the normal human prostate.

Prostates from eight adult males (age range 17-63 years) were employed in this investigation. Six glands were obtained from multiorgan transplantation donors at the time of organ harvesting, and two additional glands, at routine post-mortem. Microscopic examination has shown that the majority of acini in the peripheral parts of the gland were individually relatively small and lined by an epithelium two to three cells in thickness. In contrast, acini in the central part of the gland were usually large and contained numerous prominent epithelial folds within the lumen. On the basis of morphology, a clear distinction between peripheral and central acini was not observed. The distribution of autonomic ganglia both within and adjacent to the prostate was studied, and nerve cell bodies containing both acetylcholinesterase (AChE) activity and neuropeptide immunoreactivity were identified. The distribution and density of AChE-positive nerves associated with smooth muscle in either the peripheral or central parts of the prostate were indistinguishable. In addition, the majority of acini in peripheral and central regions possessed a rich subepithelial plexus of autonomic nerves. VIP-positive nerve fibers were found in relation to the epithelium lining acini in central and peripheral regions of the gland. In contrast, nerves possessing NPY immunoreactivity occurred only in relation to the smooth muscle trabeculae of the prostate.

Acetylcholinesterase