共查询到20条相似文献,搜索用时 31 毫秒
1.
Kalman Kovacs Eva Horvath Michael O. Thorner Alan D. Rogol 《Virchows Archiv : an international journal of pathology》1984,403(1):77-86
Summary An 11-year-old girl, with the McCune-Albright syndrome, exhibited fibrous dysplasia of several bones, skin pigmentation, precocious puberty, growth hormone hypersecretion, acromegaly and hyperprolactinemia. Histologic, immunocytologic and ultrastructural investigation of the surgically-removed pituitary showed massive mammosomatotroph hyperplasia. Since no adenoma was found, the abundance of these bihormonal cells, capable of producing both growth hormone and prolactin, was implicated in the causation of growth hormone and prolactin excess. Somatoliberin overproduction and/or somatostatin and dopamine deficiency could not account for the hypophysial abnormality, since changes in secretory rates of these hypothalamic hormones would lead to proliferation of mature somatotrophs and lactotrophs, rather than mammosomatotrophs. In our patient, a congenital hypothalamic malfunction might have been accompanied by hypersecretion of an unidentified releasing factor, resulting in pathologic differentiation of the pituitary and mammosomatotroph hyperplasia. Alternatively, mammosomatotroph hyperplasia may have been due to an inherent genetic or embryonic defect affecting primarily the pituitary. According to this interpretation, the pituitary lesion represented yet another developmental error in the setting of the McCune-Albright syndrome. 相似文献
2.
A 24-yr-old woman with amenorrhea, galactorrhea, hyperprolactinemia, and sellar mass underwent transsphenoidal surgery. Histologic,
immunohistochemical, and electron microscopic investigation revealed a well-differentiated, sparsely granulated prolactin
(PRL) cell adenoma of the pituitary showing conclusive PRL immunoreactivity. In the nontumorous adenohypophysis PRL cell hyperplasia
was noted. Marked differences were evident between the neoplastic and hyperplastic areas. The tumor consisted of sparsely
granulated PRL cells immunoreactive only for PRL. As demonstrated by immunoelectron microscopy, the hyperplastic are a comprised
monohormonal sparsely granulated PRL cells as well as bihormonal mammosomatotrophs immunoreactive for both PRL and growth
hormone. The MIB-1 index was higher whereas microvessel density was lower in the adenoma as compared with the hyperplastic
area. In addition, the nontumorous area showed lymphocytic infiltration whereas inflammatory reaction was not seen in the
adenoma. This case represents a rare association of a PRL cell adenoma and PRL cell hyperplasia. The fact that these two lesions
were contiguous in the surgically removed material raises the possibility that hyperplasia can precede and transform into
adenoma. 相似文献
3.
Safraz Mohammed Luis V. Syro Bernd W. Scheithauer Alberto Abad Humberto Uribe Fabio Rotondo Eva Horvath Michael Cusimano Kalman Kovacs 《Endocrine pathology》2009,20(1):41-45
Peliosis is characterised by multiple blood-filled lakes or cavities within parenchymatous organs. Typically found in the
liver, spleen, bone marrow and lymph nodes, it has also been described in other organs such as lungs, kidneys, parathyroids
and pancreas. The mechanism responsible for the development of peliosis remains unknown. (1) A 69 year-old man with a 6-year
history of acromegaly underwent transsphenoidal surgery for pituitary adenoma. Morphologic findings demonstrated a plurimorphous
plurihormonal pituitary adenoma consisting of somatotrophs, lactotrophs and mammosomatotrophs. The tumor contained several
blood-filled cavities characteristic of peliosis. (2) A 61-year-old man with a prolactin-producing pituitary adenoma who underwent
transsphenoidal surgery. In the tumor, peliosis was noted. Peliosis in a pituitary adenoma is an intriguing finding. The question
arises whether it represents vasculogenic mimicry. 相似文献
4.
Growth hormone (GH) and prolactin (PRL) gene expression and immunoreactivity in GH- and PRL-producing human pituitary adenomas 总被引:3,自引:0,他引:3
Jie Li Lucia Stefaneanu Kalman Kovacs Eva Horvath Harley S. Smyth 《Virchows Archiv : an international journal of pathology》1993,422(3):193-201
Summary Growth hormone(GH)-producing pituitary adenomas are morphologically heterogeneous and frequently contain not only GH immunoreactivity but also variable numbers of prolactin (PRL) immunopositive cells. Paraffin sections of 59 surgically removed GH- and/or PRL-producing adenomas classified by histology, immunocytochemistry (ICC) and electron microscopy were studied using in situ hybridization (ISH) for GH and PRL mRNA and combined with ICC for the coded hormones. Somatotroph adenomas (10 densely and 10 sparsely granulated tumours) and mammosomatotroph adenomas (10 cases) contained both GH mRNA and GH immunoreactivity. In 4 densely and 4 sparsely granulated somatotroph adenomas and 4 mammosomatotroph adenomas, only GH mRNA and its product were found. In 28 cases (6 densely and 6 sparsely granulated somatotroph adenomas, 10 mixed somatotrophlactotroph adenomas and 6 mammosomatotroph adenomas) both GH and PRL mRNA were present, although no PRL immunoreactivity was not in 2 densely granulated somatotroph adenomas. In these cases, ISH for PRL mRNA combined with GH immunostaining revealed the presence of variable numbers of mammosomatotrophs. In 9 acidophil stem cell adenomas only PRL mRNA and its product were found; one tumour expressed both GH and PRL mRNA and their products. Nine lactotroph adenomas contained only PRL mRNA and PRL immunoreactivity. The results show that GH and/or PRL mRNA content could not be correlated with ICC for coded proteins and ultrastructural features. The mammosomatotrophs were more numerous using ISH when compared with ICC. Somatotroph, mammosomatotroph and mixed adenomas are closely related and they can be considered to represent one basic tumour type originating in a cell committed to GH production. This may undergo clonal differentiation towards a mammosomatotroph and further to the lactotroph line. The results also indicate that lactotroph adenomas arise in a cell committed to PRL production. Acidophil stem cell adenomas seem to be more closely related to lactotroph cells than somatotroph. 相似文献
5.
6.
Hyperplasia of pituitary thyrotrophs is often associated with hypothyroidism. In this study, the effects of thyroxine and
17β-estradiol on thyrotroph hyperplasia was analyzed using a hypothyroid mouse model resulting from targeted disruption of
the glycoprotein hormone α-subunit (αSU) gene, which leads to lack of functional thyroid-stimulating hormone (TSH), luteinizing
hormone (LH), and follicle-stimulating hormone (FSH) and underdevelopment of the thyroid and gonads. Thyroxine replacement
for 2 mo resulted in a decrease in the relative percent of thyrotrophs and an increase of lactotrophs and somatotrophs numbers
to normal values. A twofold increase in the relative percent of gonadotrophs was observed compared to wild-type mouse pitutary.
Treatment for 2 mo with 17β-estradiol led to an increase in lactotroph numbers to normal levels, but had no influence on thyrotroph
hyperplasia. Rearrangement of the hyperplastic pituitary phenotype after hormonal replacement proceeded without any evidence
of pituitary cell necrosis. A slight increase in apoptotic cell death was observed in hormone-treated pituitaries, and this
was localized to TSH cells by double-labeling experiments. Chronic thyroxine treatment resulted in increased expression of
Bcl-2 protein in hypertrophied pituitary cells, whereas 17β-estradiol increased expression of Bad protein in prolactin cells.
These results suggest that apoptotic cell death is involved in reversal of thyrotroph hyperplasia in the presence of thyroid
hormone. Thyroxine and 17β-estradiol may influence cell death in this model by regulating expression of the Bcl-2 protein
family in a cell-type specific manner. 相似文献
7.
Vidal S Horvath E Kovacs K Cohen SM Lloyd RV Scheithauer BW 《Virchows Archiv : an international journal of pathology》2000,436(1):43-51
In patients with protracted primary hypothyroidism, the pituitary is enlarged due to the lack of feedback inhibition by thyroid
hormone. In the present work, adenohypophysial biopsies from three women with protracted primary hypothyroidism were investigated
by routine histology, immunocytochemistry, double immunostaining, immunoelectron microscopy, and combined immunocytochemistry
– in situ hybridization. These methods confirmed the presence of massive thyrotroph hyperplasia and the formation of ”thyroidectomy”
or ”thyroid deficiency” cells. A number of thyroidectomy cells were found to be immunoreactive for growth hormone (GH). Double
immunostaining and immunoelectron microscopy revealed the presence of bihormonal cells containing both GH and thyroid stimulating
hormone (TSH). Immunostaining combined with in situ hybridization revealed GH immunoreactive cells expressing TSH mRNA as
well as TSH immunopositive cells expressing GH mRNA. Our findings provide conclusive evidence that somatotrophs may transform
to thyrotrophs. Thus, in addition to multiplication of thyrotrophs, transdifferentiation of GH cells to thyrotrophs contributes
to the increase of TSH-producing cells. The presence of such bihormonal cells best termed ”thyrosomatotrophs” supports the
concept that adenohypophysial cells are not irreversibly committed to the production of one single hormone and that their
phenotype can change in response to functional demand.
Received: 16 March 1999 / Accepted: 4 July 1999 相似文献
8.
P.D. Cairns D.J. McComb E. Horvath K. Kovacs J.V. Milligan S. Szabo 《Experimental and molecular pathology》1984,41(3):298-308
In pituitary lactotrophs of female Sprague-Dawley rats given cysteamine (300 mg/kg, per os/day) for 7 days, forming granules were increased in number and contained many separate electron-dense structures suggesting crinophagy. Compared to control values, cysteamine treatment caused no change in blood prolactin (PRL) levels, measured by radioimmunoassay (RIA). 17β-Estradiol (50 μg, sc/day) for 7 days, induced lactotroph hyperplasia and increased blood PRL levels which were unaffected by simultaneous cysteamine administration. The ultrastructural changes did not reflect those due to bromocriptine suppression of secretory activity, and supported the concept that cysteamine altered lactotroph morphology by an unknown mechanism. In pituitary gonadotrophs following cysteamine treatment, increased electron lucency of luminal contents of dilated rough endoplasmic reticulum was noted; however, blood luteinizing hormone (LH) levels did not differ from those of control values. In ovariectomized rats, cysteamine suppressed castration cell formation and reduced blood LH levels, suggesting an interference with the cell's ability to respond to GnRH stimulation. The morphologic effects of cysteamine appeared to be selective to lactotrophs and gonadotrophs, and were not secondary to vascular impairment, as capillary endothelial cells were undamaged. 相似文献
9.
Pituitary Sex Steroid Receptors: Localization and Function 总被引:2,自引:0,他引:2
Stefaneanu L 《Endocrine pathology》1997,8(2):91-108
10.
Proliferation of somatotrophs and mammotrophs in the rat pituitary during late fetal and postnatal periods up to 4 weeks after birth was quantitatively studied with the double immunostaining of bromodeoxyuridine and the hormones produced by them. Somatotrophs were first detected in 18.5-day fetuses and rapidly increased in number throughout the periods studied. The cells labeled with both anti-BrdU and anti-GH were few in number until shortly before birth and then increased conspicuously during the first 10 days after birth. Mammotrophs were detected at gestational day 19.5 but they were few until the second week after birth, when their number began to increase rapidly. The percentage of the number of the cells double-labeled with both anti-BrdU and anti-GH to all somatotrophs was 8.3% at the most. This was about the same as that of corticotrophs during the late fetal period and that of thyrotrophs in the early postnatal period. In contrast, the percentage of double-labeled cells to all mammotrophs was 3.8% as a maximum, which is lower than the values for somatotrophs, corticotrophs, or thyrotrophs, indicating a smaller contribution of mitosis to mammotroph proliferation. It is possible that this smaller contribution is compensated for by transdifferentiation of cells committed to become the somatotroph lineage. However, coexistence of GH and PRL was not observed in the present material. 相似文献
11.
Overlease RL Bauer RA Angleson JK 《Pflügers Archiv : European journal of physiology》2005,449(5):458-462
The secretion of peptide hormones during exocytosis of an individual vesicle can result in either complete discharge of vesicle content or can occur in a partial manner in which some hormone is retained during transient fusion. In anterior pituitary lactotrophs, the retained hormone prolactin was internalized and recycled into a pool of vesicles that underwent preferential use during subsequent exocytic stimulations [Bauer et al., (2004) J Cell Sci. 117:2193–2202]. The aim of the present study was to determine whether retention and preferential recycling of retained hormones occurred in other anterior pituitary cells. Stimulation of somatotrophs with high K+ resulted in 50 discrete puncta per cell that were positive for growth hormone immunoreactivity. Identical stimulation of corticotrophs resulted in 150 puncta per cell that were anti-adrenocorticotrophic hormone (ACTH) positive. However, unlike what was observed for lactotrophs, the number of structures containing retained growth hormone and ACTH decreased to less than 10% of the initial value in 80 min in somatotrophs and in less than 10 min in corticotrophs. Our results indicate that functional recycling of retained hormones is not shared by all anterior pituitary cell types. 相似文献
12.
Evidence for growth hormone (GH) autoregulation in pituitary somatotrophs in GH antagonist-transgenic mice and GH receptor-deficient mice
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Asa SL Coschigano KT Bellush L Kopchick JJ Ezzat S 《The American journal of pathology》2000,156(3):1009-1015
Growth hormone (GH) modulates the hypothalamic release of somatostatin and GH-releasing hormone; however, there has been no evidence of GH autoregulation on the pituitary somatotroph. To determine the effects of GH on its own regulation, we examined the pituitaries of giant transgenic mice expressing a GH agonist (E117L), dwarf transgenic mice expressing a GH antagonist (G119K), and dwarf mice devoid of the GH receptor/binding protein (GHR/BP). In the E117L transgenic mice, the number and distribution of pituitary GH-immunoreactive cells were unchanged from nontransgenic littermate controls; an ultrastructural examination revealed typical, densely granulated somatotrophs. In contrast, the pituitaries of the G119K mice contained both moderately granulated somatotrophs and a sparsely granulated (SG) population with well-developed synthetic organelles and a distinct juxtanuclear globular GH-staining pattern. GHR/BP-deficient mice exhibited a marked reduction in the intensity of cytoplasmic GH immunoreactivity; however, prominent GH staining in the juxtanuclear Golgi was seen. GH-immunoreactive cells were increased in number, and the reticulin network pattern was distorted; stains for proliferating cell nuclear antigen confirmed mild hyperplasia. Electron microscopy showed that the somatotrophs were hyperactive SG cells with prominent endoplasmic reticulum membranes, large Golgi complexes, and numerous mitochondria. These findings are consistent with synthetic and secretory hyperactivity in pituitary somatotrophs due to the reduced GH feedback regulation. The changes are most striking in animals that are devoid of GHR/BP and less marked in animals expressing a GH antagonist; both models had reduced insulin-like growth factor-I levels, but the more dramatic change in the GHR/BP animals can be explained by abrogated GH signaling. This represents the first evidence of direct GH feedback inhibition on pituitary somatotrophs, which may have implications for the use of GH analogs in different clinical settings. 相似文献
13.
Zargar AH Wani AI Laway BA Masoodi SR Salahuddin M 《The Journal of the Association of Physicians of India》1998,46(5):474-475
In this report we describe an unusual case of postpartum pituitary necrosis who had clinical and biochemical suggestion of decreased thyrotroph, somatotroph, lactotroph, and corticotroph reserve but continued to have regular ovulatory menstrual cycles. 相似文献
14.
Saeger W 《Der Pathologe》2003,24(4):255-264
Pituitary adenomas must be clearly differentiated from other tumors of the sellar region (especially meningiomas, granular cell tumors, chordomas and germinomas), which may look very similar. The sub-classification of adenomas depends on the methods used, in particular the immunostaining for pituitary hormones. This sub-classification is not necessary in every case, but must be performed if unusual findings are observed during surgery or if surgery is unsuccessful and radiation or drug-therapy is planned. Special structures and non-immunohistochemical stainings are very helpful for typing adenomas. We differentiated monohormonal densely or sparsely granulated GH-cell adenomas, monohormonal sparsely or very rarely densely granulated prolactin cell adenomas, monohormonal densely or sparsely ACTH-cell adenomas, monohormonal TSH-cell adenomas and FSH/LH cell adenomas from bihormonal adenomas of mammosomatotroph or GH/prolactin cell type or of the acidophil stem cell adenoma type. The number of plurihormonal adenomas decreased with the use of improved monoclonal antibodies. Clinically inactive adenomas are classified as null cell adenomas, oncocytic adenomas or FSH/LH-cell adenomas. These appear as subtypes of one entity deriving from the gonadotroph cell type. Craniopharyngiomas are classified into adamantinous and papillary types, which are not only structurally but also clinically different. If adamantinous craniopharyngiomas show very strongly regressive changes, immunostaining for keratin may be necessary to identify the squamous epithelia for the demonstration of craniopharyngioma. 相似文献
15.
Jentoft ME Osamura RY Kovacs K Lloyd RV Scheithauer BW 《Virchows Archiv : an international journal of pathology》2012,461(2):221-225
Primary hypothyroidism causes adenohypophysial hyperplasia via stimulation by hypothalamic thyrotropin-releasing hormone (TRH). The effect was long thought to simply result in thyroid-stimulating hormone (TSH) and prolactin (PRL) cell hyperplasia, an increase in TSH and PRL blood levels with resultant pituitary enlargement, often mimicking adenoma. Recently, it was shown that transformation of growth hormone (GH) cells into TSH cells takes place in both clinical and experimental primary hypothyroidism. Such shifts from one cell to another with a concomitant change in hormone production are termed "transdifferentiation" and involve the gradual acquisition of morphologic features of thyrotrophs ("somatothyrotrophs"). We recently encountered a unique case of pituitary hyperplasia in a 40-year-old female with primary hypothyroidism wherein increased TSH production was by way of PRL cell recruitment. The resultant "lactothyrotrophs" maintained TSH cell morphology (cellular elongation and prominence of PAS-positive lysosomes) but expressed immunoreactivity for both hormones. No co-expression of GH was noted nor was thyroidectomy cells seen. This form of transdifferentiation has not previously been described. 相似文献
16.
Iwao Nakayama Peter A. Nickerson Lee L. Bernardis Takeshi Matsuo 《Pathology international》1974,24(5):569-594
The response of rat pituitary somatotrophs to transplantation of the MtT-W10 pituitary tumor and prolonged treatment with large doses of purified bovine growth hormone was examined. The effects of hypo-thalamic lesions on the somatotrophs were also studied.
Involution occurred in somatotrophs of the anterior pituitary of rats bearing a transplantable tumor. The changes in the somatotrophs were observable at 4 weeks and consisted of smaller cells and fewer secretory granules.
Administration of growth hormone produced a triphasic response; (1) increased cross-sectional area of cell, increased size and number of secretory granule, (2) return of parameters to normal levels, and (3) suppression of somatotrophs by exogenous growth hormone.
Following destruction of ventromedial nucleus (VMN), the number of secretory granules per somatotroph increased. Concomitantly, there was an enlargement of the mean diameter as well as an increase in the mean surface area of the somatotrophs. After destruction of dorsomedid nucleus (DMN), the number of secretory granules decreased rapidly and reached the lowest level. Two days after the operation, the secretory granules re-accumulated very slowly in the cytoplasm but remained below control level. Accompanying the decreased granule count, the mean diameter of the largest granule was smaller than that of the controls during all experimental periods. 相似文献
Involution occurred in somatotrophs of the anterior pituitary of rats bearing a transplantable tumor. The changes in the somatotrophs were observable at 4 weeks and consisted of smaller cells and fewer secretory granules.
Administration of growth hormone produced a triphasic response; (1) increased cross-sectional area of cell, increased size and number of secretory granule, (2) return of parameters to normal levels, and (3) suppression of somatotrophs by exogenous growth hormone.
Following destruction of ventromedial nucleus (VMN), the number of secretory granules per somatotroph increased. Concomitantly, there was an enlargement of the mean diameter as well as an increase in the mean surface area of the somatotrophs. After destruction of dorsomedid nucleus (DMN), the number of secretory granules decreased rapidly and reached the lowest level. Two days after the operation, the secretory granules re-accumulated very slowly in the cytoplasm but remained below control level. Accompanying the decreased granule count, the mean diameter of the largest granule was smaller than that of the controls during all experimental periods. 相似文献
17.
Matilde Lombardero res Quintanar-Stephano Sergio Vidal Eva Horvath Kalman Kovacs Ricardo V. Lloyd Bernd W. Scheithauer 《Journal of anatomy》2009,214(2):235-244
Estrogens are known to cause pituitary enlargement and lactotroph proliferation. They also modulate pituitary angiogenesis and induce tumor formation. Pituitary grafts, due to the loss of hypothalamic dopamine, also show lactotroph hyperplasia. We investigated the role of estrogen on rat pituitary autograft vascularization by light and transmission electron microscopy, and assessed prolactin (PRL) blood levels, microvessel density (MVD) and cell proliferation using the BrdU labeling index. All adenohypophysial cell types were identified by immunohistochemistry (streptavidin-biotin-peroxidase complex method). The proangiogenic factors, vascular endothelial growth factor (VEGF), its receptor Flk-1, and hypoxia inducible factor-1α (HIF-1α) were similarly demonstrated. The prevalence of lactotrophs, as well as more intense staining for VEGF, Flk-1 and HIF-1α, was noted in those grafts exposed to estrogen, mainly in the area surrounding the central necrotic core. Immunostaining showed Flk-1 expression increased in endothelial cells of the estrogen-exposed grafts as compared with those unexposed. In contrast to the grafts not exposed to estrogen, in the estrogen-exposed grafts, only fenestrated endothelium could be demonstrated, suggesting that estrogen induces fenestration of newly formed capillaries. There was an increase in blood PRL levels in the estrogen-treated groups as compared with controls. Both MVD and BrdU labeling indices were higher in grafts exposed to estrogen, especially after 4 weeks. Our results suggest that estrogen administration not only enhances the expression of proangiogenic factors in the pituitary grafts but also induces their expression at earlier stages, leading to rapid neoformation of purely fenestrated capillaries. 相似文献
18.
Shozo Yamada Lucia Stefaneanu Eva Horvath Kalman Kovacs Kesava Reddy 《Endocrine pathology》1993,4(1):34-39
A 24-year-old woman with a large pituitary adenoma had amenorrhea and galactorrhea, but no physical stigmata of acromegaly
despite slightly elevated serum growth hormone (GH) and normal serum prolactin (PRL) levels. Subtotal removal of the tumor
cured galactorrhea and resulted in normalization of serum GH concentration. The question is raised whether amenorrhea and
galactorrhea were related to excessive GH production in this patient. Absence of acromegaly might have been due to the short
duration of the disease. The tumor was a chromophobic, periodic acid-Schiff-negative adenoma. Immunocytochemistry and in situ
hybridization revealed focal GH immunoreactivity and diffuse, weak signal for GH messenger RNA. By electron microscopy, the
tumor showed no features of GH or PRL-producing adenomas. Two different cell types could be distinguished: the majority were
similar to null cells, whereas a small number of cells resembled somatotrophs and lactotrophs, possessing many secretory granules
and exhibiting exocytosis. On the basis of its ultrastructure, this tumor can be classified as an atypical acidophil cell
line adenoma in which adenomatous null cells transformed to the differentiated cells capable of producing GH. 相似文献
19.
Sergio Vidal Luis Syro Eva Horvath Humberto Uribe Kalman Kovacs 《Ultrastructural pathology》1999,23(3):141-148
Momomorphous pituitary adenomas expressing several hormones by immunocytochemistry are common, whereas adenomas displaying multiple immunoreactivities and consisting of more than one morphologic cell types are rare. Three such unusual pituitary adenomas, surgically removed from two patients with acromegaly and one patient with hyperprolactinemia, were investigated by histology, immunocytochemistry, transmission electron microscopy, as well as immunoelectron microscopy using double immunogold labeling. Immunocytochemistry revealed variable degrees of immunoreactivities for growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (beta-TSH), and alpha-subunit of glycoprotein hormones in all three tumors. The three adenomas consisted of phenotypically diverse cell populations as documented by transmission electron microscopy. In addition to monohormonal GH cells, immunoelectron microscopy demonstrated numerous cells colocalizing GH and PRL or GH and beta-TSH, and rarely PRL and beta-TSH in tumors of acromegalics. The adenoma causing hyperprolactinemia consisted chiefly of mammosomatotrophs colocalizing PRL and GH, whereas beta-TSH labeling was scant. The three tumors in the study were selected from a cluster of five plurimorphous plurihormonal adenomas received from the same locale where they accounted for an unprecedented 21% of adenomas producing GH and/or PRL. The enhanced susceptibility to develop plurimorphous adenomas of the acidophil cell line may have a genetic basis in the stable population the patients came from. 相似文献