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The neurotransmitter properties of the sympathetic innervation of sweat glands in rat footpads have previously been shown to undergo a striking change during development. When axons first reach the developing glands, they contain catecholamine histofluorescence and immunoreactivity for catecholamine synthetic enzymes. As the glands and their innervation mature, catecholamines disappear and cholinergic and peptidergic properties appear. Final maturation of the sweat glands, assayed by secretory competence, is correlated temporally with the development of cholinergic function in the innervation. To determine if the neurotransmitter phenotype of sympathetic neurons developing in vivo is plastic, if sympathetic targets can play a role in determining neurotransmitter properties of the neurons which innervate them, and if gland maturation is dependent upon its innervation, the normal developmental interaction between sweat glands and their innervation was disrupted. This was accomplished by a single injection of 6-hydroxy-dopamine (6-OHDA) on Postnatal Day 2. Following this treatment, the arrival of noradrenergic sympathetic axons at the developing glands was delayed 7 to 10 days. Like the gland innervation of normal rats, the axons which innervated the sweat glands of 6-OHDA-treated animals acquired cholinergic function and their expression of endogenous catecholamines declined. The change in neurotransmitter properties, however, occurred later in development than in untreated animals and was not always complete. Even in adult animals, some fibers continued to express endogenous catecholamines and many nerve terminals contained a small proportion of small granular vesicles after permanganate fixation. The gland innervation in the 6-OHDA-treated animals also differed from that of normal rats in that immunoreactivity for VIP was not expressed in the majority of glands. It seems likely that following treatment with 6-OHDA sweat glands were innervated both by neurons that would normally have done so and by neurons that would normally have innervated other, noradrenergic targets in the footpads, such as blood vessels. Contact with sweat glands, therefore, appears to suppress noradrenergic function and induce cholinergic function not only in the neurons which normally innervate the glands but also in neurons which ordinarily innervate other targets. Effects of delayed innervation were also observed on target development. The appearance of sensitivity to cholinergic agonists by the sweat glands was coupled with the onset of cholinergic transmission.(ABSTRACT TRUNCATED AT 400 WORDS)
A study was conducted to compare results of transrectal ultrasound with pathologic findings on 116 patients who underwent radical prostatectomy for treatment of prostate cancer. In 96% (111 of 116), transrectal ultrasound guided biopsies of a hypoechoic lesion proved cancer; seven patients had known Stage A cancer; one patient had cancer detected by palpation and not detected by ultrasound. Cancers in the outer gland (peripheral and central zones) were compared with cancers in the inner gland (transition zone) by both ultrasound and pathology. Forty-eight percent (52 of 108) of cancers originating in the outer gland showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the outer gland were the prostatic capsule (38%), anterior fibromuscular stroma (5%), seminal vesicle (18%), the base of the gland at the neurovascular bundle (21%), and the apex (31%). Twenty-two percent (17 of 54) of cancers originating in the inner gland (transition zone) showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the inner gland were the anterior fibromuscular stroma (6%) and apex (11%). Both histologic and biologic differences between outer and inner gland cancers were found when tumor size was controlled. Gleason scores were significantly different for inner and outer gland cancers, with mean scores of 6.2 +/- 1.6 and 7.4 +/- 0.9, respectively. An odds ratio of 8.6 confirmed the increased risk of extraprostatic extension for outer gland cancer. Outer gland cancers showed increased aggressive behavior of both histologic and biologic nature. The difference in biologic aggressiveness of outer and inner gland cancers has definite implications for treatment options. Use of other diagnostic parameters, such as DNA ploidy, may help to determine which cancers to treat and when to treat them; this may have more relevance for cancers originating in the inner gland. Strategic transrectal ultrasound guided biopsy affords accurate tumor mapping and staging when modes of internal spread and escape of cancer from both outer and inner gland are known. Thus, transrectal ultrasound may be our "window of observation" through which additional research may explain the histologic and biologic discrepancies between outer and inner gland cancers.
Apocrine sweat glands in the circumanal glands of the dog are not connected morphologically with the lobules of the circumanal glands. However, an apparent functional association has been demonstrated and it is possible that the apocrine sweat glands might serve as excretory ducts for degenerated polyhedral cells of the circumanal glands. In this study, we examined the ultrastructure of the apocrine sweat glands in the circumanal glands of the dog in an effort to define more precisely the relationship between the apocrine sweat glands and the circumanal glands. Paraffin sections stained with azan and sections after immunohistochemical staining with antibodies against actin were examined by light microscopy. Samples fixed by aldehyde perfusion were examined with the electron microscope. Diameters of apocrine sweat glands and height of cells in the secretory epithelium varied considerably. Immunohistochemical staining for actin was weakly positive in the supranuclear regions of secretory cells and very intense in myoepithelial cells. In secretory cells, the endoplasmic reticulum was well-developed. Multivesicular bodies were abundant and were discharged into lumens. Apocrine secretion and exocytosis were observed at luminal surfaces of secretory cells. There were three types of large granule in the cytoplasm: giant mitochondria without cristae; membrane-enclosed globules with or without myelin-like contents; and electron-dense, homogeneous, globular structures. Luminal surfaces were always covered with microvilli, and extensive folding of the cell membrane was found in basal regions. Bundles of actin filaments were dispersed throughout the cytoplasm. In the lumens of apocrine tubules, we observed shed secretory cells with well-preserved normal fine structures. We also noted the differentiation of secretory cells that was due to cell renewal. Apocrine sweat glands in the circumanal glands of the dog appear to be more active than those on the general body surface in terms of apocrine secretion, exocytosis, and the release of multivesicular bodies. Shed secretory cells containing large granules, as well as degenerated polyhedral cells from the circumanal glands, might contribute, to some extent, to the subtle composition of sweat from these apocrine sweat glands.
Mucins of the gastroduodenal junction are secreted by the mucous surface and mucus-producing glandular cells in the stomach, and by goblet cells and Brunner's glands in the duodenum. Developmental studies have demonstrated that Brunner's glands can arise from undifferentiated gastric epithelium and/or intestinal epithelium in the proximal duodenum. The aim of this study was to investigate the carbohydrate composition of mucins from this region and compare it with that of mucins from Brunner's glands to evaluate the probable evolution of mucins from these glands. Toward that end, paraffin sections from 13 mammalian species were stained by classic carbohydrate histochemistry and treated with 13 lectins. In general, the mucous surface cells of the stomach, pyloric glands, duodenal goblet cells, and Brunner's glands secretory epithelium had different lectin-binding patterns. However, the lectin-binding profile of the secretory epithelium of Brunner's glands resembled that of pyloric glands more closely than that of duodenal goblet cells and mucous surface cells of the stomach. Mucins from Brunner's glands and pyloric glands showed a greater terminal carbohydrate residue diversity than those of gastric mucous surface cells or duodenal goblet cells. The lectin-binding profile argues for the evolution of similar mucins from the epithelia of Brunner's glands and pyloric glands. The greater diversity of carbohydrate residues in mucins secreted by Brunner's glands suggests that their mucus is more adaptable. This may explain why Brunner's glands metaplasia rather than goblet cell metaplasia is seen in the mucosa adjacent to chronic intestinal ulcers.
AIM: The most frequent non-thyroidal complication of high-dose (131)I therapy for thyroid carcinoma is salivary gland dysfunction, which may be transient or permanent. In this study, we assessed radioiodine-induced permanent salivary gland dysfunction using quantitative salivary gland scintigraphy. METHODS: Salivary scintigraphy was performed with (99m)Tc-pertechnetate on 50 thyroid carcinoma patients who had been given radioiodine for thyroid ablation; 20 normal subjects were imaged as the control population. Dynamic scintigraphy was performed and time-activity curves for four major salivary glands were generated. The glandular functional parameters maximum secretion, time at maximum count and uptake ratio of the parotid and submandibular glands were calculated. Correlation of the administered dose and subjective symptoms with findings of salivary gland scintigraphy was evaluated. RESULTS: The maximum secretion and uptake ratio were decreased in 46% and 42% of patients who received radioiodine therapy, respectively. Salivary gland dysfunction correlated well with the administered dose. The parotid glands were more affected than the submandibular glands. Fifty-two per cent of patients were symptomatic, 69.23% of whom showed salivary gland dysfunction. CONCLUSION: Parenchymal damage to the salivary glands induced by radioactive iodine treatment can be evaluated by salivary gland scintigraphy. The impairment was worse in parotid glands and increased with the total dose. The maximum secretion and uptake ratio were found to be sufficiently sensitive to distinguish the severity of the damage.
This is a histologic study using the peroxidase-antiperoxidase (PAP) method for demonstration of estradiol, testosterone, dihydrotestosterone and progesterone in the normal thyroid gland and papillary carcinoma of the thyroid gland as well as in the normal parotid gland and pleomorphic adenomas. The results show that the normal follicular epithelia of the thyroid gland and the intercalated, striated ducts in the parotid gland stained for sex hormones. Estradiol was positive in both thyroid and parotid gland tissue in females and males. In females, testosterone and dihydrotestosterone were not recognized in the thyroid gland tissue and were only weakly present or negative in parotid gland tissue. In males, both testosterone and dihydrotestosterone were positive. Papillary carcinoma of the thyroid gland and pleomorphic adenoma of the parotid gland were positive for estradiol but not for testosterone or dihydrotestosterone. This suggests that there is a sex difference in the influence of sex hormones on the normal thyroid and parotid glands, and that estradiol exerts an influence on papillary carcinoma of the thyroid gland and pleomorphic adenoma of the parotid gland.
The major salivary glands of mammals are represented by three pairs of organs that cooperate functionally to produce saliva for the oral cavity. While each type of gland produces a signature secretion that complements the secretions from the other glands, there is also redundancy as evidenced by secretion of functionally similar and, in some cases, identical products in the three glands. This, along with their common late initiation of development, in fetal terms, their similarities in developmental pattern, and their proximate sites of origin, suggests that a common regulatory cascade may have been shared until shortly before the onset of overt gland development. Furthermore, occasional ectopic differentiation of individual mature secretory cells in the "wrong" gland suggests that control mechanisms responsible for the distinctive cellular composition of each gland also share many common steps, with only minor differences providing the impetus for diversification. To begin to address this area, we examine here the origins of the salivary glands by reviewing the expression patterns of several genes with known morphogenetic potential that may be involved based on developmental timing and location. The possibility that factors leading to determination of the sites of mammalian salivary gland development might be homologous to the regulatory cascade leading to salivary gland formation in Drosophila is also evaluated. In a subsequent section, cellular phenotypes of neonatal and adult glands are compared and evaluated for insights into the mechanisms and lineages leading to cellular diversification. Finally, the phenomena of proliferation, repair, and regeneration in adult salivary glands are reviewed, with emphasis on the extent to which the cellular diversity is reversible and which cell type other than stem cells has the ability to redifferentiate into other cell types.
Caecilians are exceptional among the vertebrates in that males retain the Mullerian duct as a functional glandular structure. The Mullerian gland on each side is formed from a large number of tubular glands connecting to a central duct, which either connects to the urogenital duct or opens directly into the cloaca. The Mullerian gland is believed to secrete a substance to be added to the sperm during ejaculation. Thus, the Mullerian gland could function as a male accessory reproductive gland. Recently, we described the male Mullerian gland of Uraeotyphlus narayani using light and transmission electron microscopy (TEM) and histochemistry. The present TEM study reports that the secretory cells of both the tubular and basal portions of the tubular glands of the male Mullerian gland of this caecilian produce secretion granules in the same manner as do other glandular epithelial cells. The secretion granules are released in the form of structured granules into the lumen of the tubular glands, and such granules are traceable to the lumen of the central duct of the Mullerian gland. This is comparable to the situation prevailing in the epididymal epithelium of several reptiles. In the secretory cells of the basal portion of the tubular glands, mitochondria are intimately associated with fabrication of the secretion granules. The structural and functional organization of the epithelium of the basal portion of the tubular glands is complicated by the presence of basal cells. This study suggests the origin of the basal cells from peritubular tissue leukocytes. The study also indicates a role for the basal cells in acquiring secretion granules from the neighboring secretory cells and processing them into lipofuscin material in the context of regression of the Mullerian gland during the period of reproductive quiescence. In these respects the basal cells match those in the epithelial lining of the epididymis of amniotes.
The development of sweat glands is a complex biological process, and the extent of cellular trafficking between epidermal stem cells and the development of sweat glands is uncertain. Therefore, we studied the synergetic development effects of stem cells, sweat glands, growth factors, and matrix metalloproteinases (MMPs) in human skin. Human fetal skin was obtained from spontaneously aborted fetuses at 11-31 weeks of gestation. Paraffin sections were cut and stained with hematoxylin and eosin or immunostained with antibodies against beta(1) integrin, keratin (K)-19 and K7, MMP-2 and -7, and epidermal growth factor. In situ hybridization was used along with semiquantitative analysis of the positive expression of these proteins to analyze for mRNA expression of MMP-2 and -7. Histological studies revealed the fetal epidermis began to form a primary epidermal ridge at gestational age 13-14 weeks and these primordial basal cells became tightly packed to take the form of multiple hillocks between 14 and 16 weeks. Furthermore, these cells gave rise to chord-like columnar buds in the embryonic epidermis, and these buds gradually migrated downward into the dermis to form juvenile sweat glands at 18-20 weeks. Mature sweat glands were found in the fetal epidermis at the end of 24 weeks. beta(1) integrin and K19 immunoreactivities were first detected in those cells that gathered together to form primary epidermal ridges, including sweat gland cords, buds, and immature sweat gland cells. The positive immunostaining for K7 appeared in early sweat gland buds at 14-16 weeks, and from then on K7 was concentrated in developing sweat gland cords or cells. At 14-16 weeks, positive epidermal growth factor, MMP-2, and MMP-7 expression was first observed weakly in developing sweat gland buds. The immunoreactivity of these proteins was then gradually increased in the developing sweat gland buds and extracellular stroma from 14 to 20 weeks. The intensity of the positive signal peaked at 20-22 weeks of gestational age. After that, the intensity of immunostaining for MMP-2 and MMP-7 proteins was gradually weakened. However, the expression of epidermal growth factor did not show an apparent decrease. These results suggest that epidermal stem cells are the source of sweat glands. Epidermal growth factor is one of the main inducers in the development and maturity of sweat gland buds or cells and the local activated MMPs may play an important role in cleaving the major matrix components in the basement membrane.
Three major disease groups emerge from a classification of the pathohistology of 2,600 salivary gland preparations in the salivary gland register (from 1965 to 1974): salivary gland tumors (41%), salivary gland inflammations (26%), and sialadenosis (6%). Mucoceles (2%) and salivary gland cysts (1.5%) are seen less often. It is diagnostically important that lymph node changes in the area of the salivary glands (lymphadenitis, lymphomas, etc.) are worked up under suspicion of a primary salivary gland disease. Sialadenosis involves a primary, vegetative neuropathy, which is accompanied by enlargement of acinar cells. Under the heading of chronic sialdenitis, we fine 50% socalled Küttner tumors of the submandibular gland, 21% chronic relapsing parotitis, 14% chronic inflammations of the minor salivary glands and the sublingual gland, and 12% immune sialadenitis (myoepithelial sialadenitis in Sjögren's syndrome and epitheloid cell sialadenitis in Heerfordts syndrome). A more than average number of immune sialadenitis cases develop into malignant lymphomas (4 cases in the salivary gland register). The 1,067 tumor cases containing of 929 epithelial tumors (87%), 89 mesenchymal tumors (hemangiomas, lymphangiomas, lipomas, neurofibromas, sarcomas) and 49 metastases or periglandular tumors. Epithelial tumors were grouped on the basis of the World Health Organization (WHO) classification. Benign tumors (71.5%) consisted of pleomorphic adenomas (51.5%) and monomorphic adenomas (50%). After the pleomorphic adenomas, cystadenolymphomas (over 10%) represented the most frequent benign salivary gland tumor. On the basis of epithelial and stromal differentiation, pleomorphic adenomas were subdividied into four subtypes (stroma-rich and stroma-poor adenomas). The malignant tumors consisted of acinar cell tumors (2.5%), mucoepidermoid tumors (6%), and carcinomas at various levels of differentiation (adenoid-cystic carcinomas, 6.5%; adenocarcinomas, 2%; squamous cell carcinomas, 2%; carcinomas in pleomorphic adenomas, 4%; miscellaneous carcinomas - salivary duct carcinomas, clear-cell carcinomas, undifferentiated carcinomas, 5.5%). Differences in age and sex distribution, localization, malignity metastases, recidivism, et
The authors examined the effects of hypoxia (8% O2 in N2) on the turnover rates of norepinephrine (NE) and epinephrine (E) in the heart, adrenal gland, submaxillary gland and stomach. The turnover rates were estimated by measuring the decrease in the content of NE and E after an i.p. injection of alpha-methyl-p-tyrosine (250 mg/kg), an inhibitor of tyrosine hydroxylase. After a 4-h exposure to hypoxia, the turnover rate of NE in the heart and those of NE and E in the adrenal gland were increased, whereas that of NE in the submaxillary gland was decreased. The turnover rate of NE in the stomach was unchanged. Pretreatment with hexamethonium, a ganglionic nicotinic receptor blocker, abolished the hypoxia-induced changes in the turnover rate of NE or E in the heart, adrenal gland and submaxillary gland. Furthermore, transection of the spinal cord at the level of C5-6 abolished hypoxia-induced alterations in the turnover rate of NE and E in the adrenal gland and submaxillary gland. In contrast, the hypoxia-induced changes seen in the heart persisted, although at a lower level, even after transection. These results show that the effects of hypoxia on the activities of the sympathoadrenal system differ depending on the organs; activities are increased in the heart and adrenal gland, decreased in the submaxillary gland and unchanged in the stomach. Furthermore, the present data suggest that hypoxia-induced alterations in the activities of cardiac sympathetic nerves originate in both the brain and spinal cord, including preganglionic neurons, whereas changes in the activities of the sympathetic nerves to the adrenal gland and submaxillary gland originate mainly in the brain.
Thirteen cases of sebaceous gland carcinoma and 10 cases of sweat gland carcinoma were studied using immunohistochemical staining for proliferating cell nuclear antigen (PCNA), c-erbB-2, and p53 to examine correlations among them, and to determine the best predictor of patient prognosis. Many sebaceous gland carcinomas and sweat gland carcinomas showed nuclear accumulation of p53, and patients with tumors showing a PCNA index (percentage of nuclei stained for PCNA) higher than 20%, and a p53 index (percentage of nuclei stained for p53) higher than 10% had short survival. Sebaceous gland carcinomas and sweat gland carcinomas showing c-erbB-2 expression had high PCNA (> 20%) and p53 (> 10%) indices, and were associated with poor prognosis. Histologically, sebaceous gland carcinomas showing a high degree of differentiation and severe nucleolar atypia had high PCNA and p53 indices. A growth pattern of small solid nests and strands, a low degree of differentiation, and the presence of lymphatic permeation in sweat gland carcinoma were often associated with high PCNA and p53 indices. These results suggest that nuclear accumulation of p53 plays an important role in the development of sebaceous gland carcinoma and sweat gland carcinoma. Assessment of PCNA and p53 indices together was very useful for prognostication of patient outcome, using cut-off values of 20% and 10%, respectively, to separate good prognosis from poor. Differentiation of sebaceous gland carcinoma, and c-erbB-2 expression by sweat gland carcinoma were significant independent prognostic indicators.
The aim of this study was to provide an appropriate experimental model to study functional changes in salivary glands using scintigraphy. Although the rabbit was frequently used for laboratory experiments, there are only a few studies that describe the exact position of its different salivary glands on the sialoscintigram. Twenty rabbits were used for the study; ten of them were anatomically dissected to provide the required topographic anatomy on the different salivary and lacrimal glands. The remaining ten animals underwent a static scintigraphy after extirpation of a particular salivary gland. Changes in the pattern of tracer uptake indicated the exact position of every gland allowing its evaluation. The results show that the 99mTcO4- uptake can only be selectively evaluated in two salivary glands, the superficial mandibular gland and the parotid gland. The superficial mandibular gland was proved to be a particularly useful model to evaluate functional changes of salivary gland parenchyma due to its well defined and high enhanced structure which allows a precise detection and measurement of the tracer uptake. Additionally, the good surgical accessibility of this gland and the existence of a well defined capsule facilitate associated histological studies of its parenchyma.
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