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Biomedical subjects

J M Hutson

Publications and source records attributed to J M Hutson.

At least 19 recordsLinked to original sources
PubMed2006

High affinity choline transporter immunoreactivity in rat ileum myenteric nerves.

Recently, an antibody against the choline transporter (CHT), an essential molecule involved in ACh uptake, was used to label cholinergic nerves in the central nervous system; however, the enteric nervous system (ENS) was not examined. The present study localised CHT immunoreactivity (CHT-IR) within the rat ileum ENS and determined whether it colocalised with immunoreactivity for markers of cholinergic, tachykinergic and nitrergic circuitry. Segments of rat ileum were fixed, prepared for sectioning or whole-mounts and incubated with anti-CHT antisera followed by a fluorescent secondary antibody. Samples were double-labelled with antibodies to nitric oxide synthase, substance P (SP), common choline acetyltransferase (cChAT) and vesicular acetylcholine transporter (VAChT). CHT-IR was present in varicosities of nerve fibres in the myenteric plexus and muscle layers of rat ileum. In the myenteric ganglia, CHT-IR was found in nerve fibres and the cytoplasm of some nerve cell bodies. In the myenteric ganglia, no CHT/cChAT-immunoreactive neurons were present. A small number of CHT/SP-immunoreactive neurons and CHT/SP-immunoreactive nerve fibres clustered around unlabelled neurons. CHT-IR colocalised with VAChT-IR in the myenteric plexus but only half of the CHT-immunoreactive myenteric nerve fibres were VAChT-immunoreactive and half of VAChT-immunoreactive fibres were CHT-immunoreactive. In the circular muscle, 75% of CHT-immunoreactive fibres were VAChT-immunoreactive. Thus, the anti-CHT antiserum labels neurons and nerve fibres in the rat ENS. It does not label cholinergic cChAT-immunoreactive neurons, although it does immunostain cholinergic VAChT-immunoreactive nerve fibres and a population of nerves that are not VAChT-immunoreactive.

Animals↗
PubMed2005

Germ cell development in the descended and cryptorchid testis and the effects of hormonal manipulation.

Germ cell development is an active process in normal testes during the first 4 years after birth, with transformation of the neonatal gonocytes into adult dark spermatogonia and then primary spermatocytes. The hormonal regulation of these changes is not fully understood, with evidence both for and against a role for gonadotrophins and androgens. Early surgical intervention in infancy aims to prevent or reverse germ cell maldevelopment. Although hormonal treatment for maldescent has been shown to be ineffective, there is still controversy over whether it may be useful as an adjunct to surgery to stimulate germ cells. Current evidence suggests that hormonal therapy may not stimulate transformation of neonatal gonocytes but may trigger prepubertal mitosis of primary spermatocytes. Further studies are required to determine the role of hormone treatment on germ cell development.

Cell Transformation, Neoplastic↗
PubMed2005

Urethral polyps in prepubertal girls.

PURPOSE: Urethral polyps in girls are included in the differential diagnosis of interlabial masses. Only 6 cases have been described in the English literature to date and etiology is uncertain. We present 5 more cases and review the literature. We also propose an etiology for urethral polyps in young girls and compare polyps between girls and boys as well as older females. MATERIALS AND METHODS: The medical records of prepubertal girls with urethral polyps seen at our hospital between 1980 and 2003, including operative reports and followup, were reviewed. A senior pathologist re-inspected the specimens to confirm the diagnosis. A MEDLINE search of urethral polyps was performed. RESULTS: We identified 5 girls 2 to 10 years old with urethral polyps. All girls presented with "vaginal" bleeding, 1 had recurrent urinary tract infections and vulvitis, 1 had urinary frequency, and 1 had painful voiding. The polyps were not site specific and were located in the distal, mid and proximal urethra. All polyps were excised and were found benign. Four girls were cured after 1 procedure, while in one girl the polyp reappeared. The patients were followed for 1 to 17 years and eventually became asymptomatic. CONCLUSIONS: Urethral polyps in prepubertal girls are probably benign. We suggest that the etiology of most of polyps in girls is similar to those in older females, that is a prolapsing urothelium that has evolved into a polyp.

Child↗
PubMed2005

Immunohistochemical localization of substance P NK1 receptor in guinea pig distal colon.

BACKGROUND: Neurokinin receptors facilitate tachykinin mediated intestinal motility and secretion. Distribution of Substance P (SP) neurokinin 1 receptor (NK1r) immunoreactivity (IR) has been previously characterized in guinea pig ileum, but not colon. This study localizes NK1rs in guinea pig distal colon. METHODS: Neurons were double labelled for NK1r and either acetylcholine transferase (ChAT), calbindin (calb), neuropeptide Y (NPY), nitric oxide synthase (NOS) or SP. The NK1r endocytosis was induced by 10(-5) mol L(-1) SP, septide, [SarMet] SP or neurokinin A. RESULTS: In guinea pig distal colon, NK1r-IR was present on 70% of submucosal neurons. Sixty-threepercent of the NK1r-IR submucosal neurons were ChAT-IR, 16% calb/SP-IR, 19% NPY-IR and 14% NOS-IR neurons. The NK1r-IR was present on 5% of myenteric neurons. Of these 63% were ChAT-IR, 16% calb-IR neurons and 25% NOS-IR. The NK1rs were also on myenteric plexus interstitial cells of Cajal and on circular muscle. CONCLUSION: In guinea pig distal colon, NK1rs were on 70% of submucosal neurons including all three secretomotor neuron subtypes and sensory neurons, suggesting NK1rs have a major role in neuronal control of mucosal reflexes. The NK1rs were on few myenteric neurons but were dense on muscle cells, suggesting NK1rs affect motility through neuro-muscular rather than neuro-neuronal transmission.

Animals↗
PubMed2005

Severe colonic diverticulitis in an adolescent with Williams syndrome.

Williams Syndrome (WS) is a condition with multisystemic involvement caused by a genetic deletion in chromosome 7. Colonic diverticulosis has been described in adults with WS; however, it has not previously been reported in adolescents with WS. We report an adolescent boy with WS who developed complicated colonic diverticulitis and briefly review the possible aetiology of diverticular disease.

Adolescent↗
PubMed2005

Characterization of the rat INSL3 receptor.

Human LGR8, initially discovered as a low-affinity relaxin receptor, has now been characterized as the INSL3 receptor. To investigate LGR8 function in the rat, an LGR8 ortholog was identified in the rat genome, and the full-length sequence was cloned and expressed. Rat LGR8 bound INSL3 with high affinity, clearly demonstrating that it is the rat INSL3 receptor. Interestingly, native rat relaxin did not activate rat LGR8, indicating that relaxin is not an endogenous ligand for rat LGR8. LGR8 mRNA expression was demonstrated in the gubernaculum at the time of testis descent and in the testis associated with germ cells.

Animals↗
PubMed2004

Ranitidine-enhanced 99mtechnetium pertechnetate imaging in children improves the sensitivity of identifying heterotopic gastric mucosa in Meckel's diverticulum.

Meckel's diverticulum is the most common congenital gastrointestinal anomaly. (99m )Technetium pertechnetate imaging (Meckel's scan) is the best noninvasive method used to diagnose this condition when heterotopic gastric mucosa (HGM) is present. Although cimetidine enhancement has been shown to improve sensitivity of the Meckel's scan, ranitidine enhancement has also been advocated; however, this recommendation is based on unpublished data. Thirty-seven children with confirmed Meckel's diverticulum were reviewed retrospectively. Of eight children with HGM in the Meckel's diverticulum who presented with profuse rectal bleeding and underwent the conventional Meckel's scan, three of them (37.5%) had a false negative study. Ranitidine, when administered either intravenously or orally for 24 h prior to the Meckel's scan, enhanced the sensitivity of this test to 87.5% in our patient cohort.

Adolescent↗
PubMed2004

Urinary diversion in children with pelvic tumors.

PURPOSE: The aim of this study was to investigate children presenting with malignant pelvic tumors obstructing the upper urinary tract. METHODS: Seventeen children with upper urinary tract obstruction by a malignant tumor were reviewed. A nephrostomy tube or Double J (DJ) stent was inserted into each obstructed urinary system and removed after tumor shrinkage and/or hydronephrosis regression. RESULTS: There were 9 boys and 8 girls in the study; the mean age and median follow-up were 5.7 years and 2.5 years, respectively. The most common obstructing tumor was rhabdomyosarcoma. Twelve children underwent diversion by nephrostomy tubes and 3 by DJ stents; 2 patients underwent resection of the tumors with ureteroureterostomy. Complications after the insertion of the stents included febrile urinary tract infections (UTI) or pyelonephritis in 4 of the children with DJ stents. In the nephrostomy group, febrile UTI developed in 3 and the tube fell out in 1, and was blocked in another. Of the 17 children, 9 have no evidence of disease, 2 are currently under treatment, and 6 died of cancer. CONCLUSIONS: The prognosis of children with malignant pelvic tumor obstructing the upper urinary system justifies urgent and optimal upper tract diversion, enabling chemotherapy to be started immediately.

Child, Preschool↗
PubMed2003

The absence of lateral fusion in cloacal partition.

BACKGROUND/PURPOSE: The mechanism by which the cloaca becomes partitioned into a dorsal rectal part and a ventral genitourinary sinus has been the subject of speculation for more than a century. Despite repeated suggestions that partitioning of the cloaca by fusion of lateral folds does not occur, the concept continues to hold sway in many student and surgical texts. The authors reviewed the histologic and 3-dimensional appearance of the urorectal septum in human and rat embryos to see if there was any evidence of lateral fusion in its formation. METHODS: Sprague-Dawley rat embryos (n = 143) were examined between 11 and 21 days' gestation and compared with human embryo sections (57 embryos) held in historical collections in Europe. Rat embryos were examined by microscopy, dissection, and serial histologic section. In addition, some specimens were sectioned in wax until the lumen of the cloaca was reached, after which they were dewaxed and the internal cavities imaged with scanning electronmicroscopy (n = 18 of 143). RESULTS: Cloacal "partitioning" resulted from a combination of growth of the mesenchyme of the hindgut and genitourinary sinus, an alteration in the position of the cloaca in relation to surrounding structures secondary to growth in the ventral, infraumbilical abdominal wall and changes in the curvature of the developing spine, and apoptosis in the dorsal wall of the cloaca with shortening of the dorsal cloacal wall. There was no septum, as it is usually defined, between the developing bladder and hindgut. There was no evidence on either histologic section or scanning electronmicroscopy of any process of fusion occurring between the 2 lateral folds within the lumen of the cloaca. CONCLUSIONS: Lateral fusion of the side walls of the cloaca does not play a role in cloacal "partition." Development of the bladder and hindgut occurs by a process that involves growth, differentiation, and remodeling.

Animals↗
PubMed2003

Cholinergic transmission to colonic circular muscle of children with slow-transit constipation is unimpaired, but transmission via NK2 receptors is lacking.

Tachykinins (TKs) colocalize with acetylcholine in excitatory motor neurones supplying human colonic circular muscle (CCM). Some children with slow-transit constipation (STC) have reduced TK-immunoreactivity in nerve terminals in CCM suggesting a deficit in neuromuscular transmission. This study aimed to test this possibility. Seromuscular biopsies of transverse colon were obtained laparoscopically from STC children (37, 17 with low density of TK-immunoreactivity). Specimens of transverse (17) and sigmoid colon (20) were obtained from adults undergoing colonic resection for cancer. CCM contractions were measured isotonically and responses to carbachol, neurokinin A (NKA) and electrical field stimulation (EFS) recorded. Carbachol and NKA-evoked contractions in adult and STC colon. Hyoscine (2 micromol L-1) significantly depressed responses to EFS in all preparations. Blockade of NK2 receptors (SR 48968, 2 micromol L-1) significantly depressed EFS-evoked contractions of adult transverse CCM, but had no effect on STC preparations. Thus, neuromuscular transmission in both adults and STC children is predominantly cholinergic and this component is unimpaired in the latter, indicating that reduced TK-immunoreactivity is not a marker for depressed cholinergic responses. Although pharmacologically responsive TK receptors are present in STC colon, we did not detect neuromuscular transmission mediated by release of TKs in these preparations.

Adolescent↗
PubMed2003

Rules for clinical diagnosis in babies with ambiguous genitalia.

Intersex disorders are rare and complex; yet, in each case of genital ambiguity, accurate and expeditious management is required of the clinician. This article reviews the embryology of sexual differentiation, from which some 'rules' of diagnosis are derived. A simplified approach to the interpretation of clinical signs in ambiguous genitalia is presented and discussed.

Female↗
PubMed2002

Gubernacular development in Müllerian inhibiting substance receptor-deficient mice.

OBJECTIVE: To determine, in mice with disrupted Müllerian inhibiting substance (MIS) receptor genes, whether MIS affects gubernacular development; MIS causes Müllerian duct regression and is proposed to be involved in the first stage of testicular descent, because gubernacular development is abnormal in humans with persistent Müllerian duct syndrome. MATERIALS AND METHODS: Ten wild-type, 11 heterozygotic and 12 homozygotic mice for MIS receptor mutations were killed at 17.5 or 18.5 days after conception or at birth, to provide serial sagittal sections of the pelvis. The amount of cremaster muscle, mitotic bodies in the gubernacular bulb, and gubernacular size were quantified by computer analysis (four mice/group). RESULTS: Müllerian ducts were present in the homozygous mutants, partially present in the heterozygotes and absent in the wild-type controls. All mice had descended testes. The cremaster muscle was significantly less developed in homozygous mutants than in wild-type controls (P < 0.001) and heterozygotes (P < 0.01) at birth. The mitotic index between the gubernacula of all groups was indistinguishable. There was no statistical difference in gubernacular area amongst the groups. Poor cremaster muscle development in homozygous mutants gave the muscle a loose mesenchymal appearance. CONCLUSIONS: Although there was an observable effect on cremaster muscle development in these mutant mice, gubernacular development and testicular descent were otherwise normal, and thus there must be other reasons for the observed differences in humans with persistent Müllerian duct syndrome.

Abdominal Muscles↗
PubMed2002

The cloacal plate: the missing link in anorectal and urogenital development.

OBJECTIVE: To determine whether differences in the embryology of the anorectal and urogenital area, previously examined in sheep, pigs, rats, rabbits and guinea pigs, producing varying conclusions, may be secondary to differences in species development. MATERIALS AND METHODS: Rat and human embryos were studied at the time of genital tubercle development and cloacal partition by standard serial-section histology, and by immunohistochemistry, dissection and scanning electron microscopy. The images obtained were compared with those previously reported for pig and sheep embryos. RESULTS: The cloacal plate, a vertically orientated midline plate of epithelial cells in the caudal half of the genital tubercle, was the key structure that varied between the different species. In rats the plate maintained a vertical height along its length, while in humans and pigs it reverted to a two-layer membrane dorsally, shortly before it degenerated to expose both the anorectal and urogenital tracts. In sheep the plate was taller ventrally than in the other species but also reverted to a short membrane dorsally that exposed the hindgut when it degenerated. The anterior part of the cloacal plate persisted in all embryos as the urethral plate, which then participated in the formation of the urethra in the male and the vestibule in the female. The animal that most closely resembled humans in anogenital development was the pig. CONCLUSIONS: The cloacal plate is the key to understanding early anorectal and urogenital development and yet it is barely recognized in published reports. An appreciation of its relevance helps to explain the variations in the described embryology of the region, and is mandatory when interpreting embryological findings in animal models of human anomalies. Given the similarities between porcine and human development, the pig may be the most legitimate animal model for the study of anorectal and urogenital anomalies in humans.

Anal Canal↗
PubMed2002

The urethral plate--does it grow into the genital tubercle or within it?

OBJECTIVE: To determine whether the urethral plate grows into the genital tubercle or develops within it. MATERIALS AND METHODS: Sprague-Dawley rat embryos were examined at 11-21 days of gestation and compared with available human embryo sections. Rat embryos were examined by a combination of light microscopy, dissection, serial histological section and immunohistochemistry. RESULTS: In rat embryos the urethral plate extended to the tip of the genital tubercle from the earliest stages of genital tubercle development. The plate formed from adherence in the sagittal plane of the inner walls of the primitive cloacal cavity. The urethral plate continued to extend to the tip of the genital tubercle throughout penile development in the male and developed a lumen ahead of the advancing perineal mesenchyme. In the female the perineal side of the urethral plate disintegrated by massive apoptosis. This loss of perineal substance allowed the genital tubercle to collapse on itself and left the urogenital opening at the base of the genital tubercle. Human embryos also showed the presence of the urethral plate at the tip of the genital tubercle throughout genital tubercle development. CONCLUSION: The urethral plate forms ab initio within the genital tubercle and extends to the tip; it does not grow into the genital tubercle as is often described. The contribution of ectodermal ingrowth to urethral development at the tip of the penis is minimal.

Animals↗
PubMed2002

In vitro analysis of esophageal atresia using a whole-embryo culture system.

BACKGROUND/PURPOSE: Administration of Adriamycin to pregnant rats leads to the development of esophageal atresia with tracheo-esophageal fistula. This defect arises from failure of the trachea to develop normally from the primitive foregut; instead,the upper foregut differentiates into trachea, then continues to the lower esophageal segment as a tracheo-esophageal fistula. Our aim was to explore the possibility of growing Adriamycin-exposed embryos using a whole-embryo culture technique and to determine whether or not esophageal atresia with tracheo-esophageal fistula could be prevented in an Adriamycin-treated rat model. METHODS: Rat embryos were exposed to Adriamycin in utero on days 6 - 9 of gestation, removed on day 10 and grown in vitro as described by New (11) for 48 hours using 100% serum from animals not exposed to Adriamycin. RESULTS: Thirty Adriamycin-exposed embryos were grown in vitro using normal serum. Histologic assessment of tracheo-esophageal development showed that 14 embryos had normal development, while 16 developed esophageal atresia. CONCLUSIONS: Growth of Adriamycin-exposed embryos was successful using "whole-embryo culture technique"; abnormal tracheo-esophageal development could in some cases be altered by removing the embryos at day 10 and exposing them to normal serum for 48 hours.

Abnormalities, Drug-Induced↗