scholarly journals Is IGSF1 involved in human pituitary tumor formation?

2015 ◽  
Vol 22 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Fabio R Faucz ◽  
Anelia D Horvath ◽  
Monalisa F Azevedo ◽  
Isaac Levy ◽  
Beata Bak ◽  
...  

IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary. Pathogenic mutations in the IGSF1 gene (on Xq26.2) are associated with X-linked central hypothyroidism and testicular enlargement in males. In this study, we tested the hypothesis that IGSF1 is involved in the development of pituitary tumors, especially those that produce growth hormone (GH). IGSF1 was sequenced in 21 patients with gigantism or acromegaly and 92 healthy individuals. Expression studies with a candidate pathogenic IGSF1 variant were carried out in transfected cells and immunohistochemistry for IGSF1 was performed in the sections of GH-producing adenomas, familial somatomammotroph hyperplasia, and in normal pituitary. We identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function, in two male patients and one female with somatomammotroph hyperplasia from the same family. Of 60 female controls, two carried the same variant and seven were heterozygous for other variants. Immunohistochemistry showed increased IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared with a GH-producing adenoma from a patient negative for any IGSF1 variants and with normal control pituitary tissue. The IGSF1 gene appears polymorphic in the general population. A potentially pathogenic variant identified in the germline of three patients with gigantism from the same family (segregating with the disease) was also detected in two healthy female controls. Variations in IGSF1 expression in pituitary tissue in patients with or without IGSF1 germline mutations point to the need for further studies of IGSF1 action in pituitary adenoma formation.

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 2963-2973 ◽  
Author(s):  
Mei Xu ◽  
Aaron J. Knox ◽  
Katherine A. Michaelis ◽  
Katja Kiseljak-Vassiliades ◽  
Bette K. Kleinschmidt-DeMasters ◽  
...  

Reprimo (RPRM), initially identified as a downstream effector of p53-induced cell cycle arrest at G2/M, is a putative tumor suppressor silenced in some types of cancer. In microarrays, the RPRM transcript was repressed 26-fold in gonadotrope (null cell) human pituitary tumors compared with normal pituitary but in the absence of changes in p53. Inhibition of RPRM mRNA was confirmed by RT-PCR in all gonadotrope tumors, most GH samples, and variably in other tumor types. Human pituitary tumors showed no evidence of abnormal promoter hypermethylation as a mechanism of RPRM repression. RPRM stable expression in gonadotrope (LβT2) and GH (GH3) pituitary cells resulted in decreased rates of cell proliferation by 55 and 30%, respectively; however, RPRM reexpression did not alter G2/M transition. In addition, RPRM increased rates of apoptosis in response to growth factor deprivation as assessed by caspase-3 cleavage and nuclear condensation. Clonagenic assays showed a 5.3- and 3.7-fold suppression of colony growth in RPRM-overexpressing LβT2 and GH3 cells, respectively, supporting its role as a tumor suppressor. In cells stably expressing RPRM mRNA, protein levels were actively suppressed due to rapid degradation through ubiquitination and proteasomal targeting. Growth factor withdrawal, as a model of cellular stress, stabilized RPRM protein levels. Together these data suggest that RPRM is transiently up-regulated at a posttranscriptional level in times of cellular stress to restrict cell survival, proliferation, and tumor formation. When RPRM is silenced as in human pituitary tumors, unrestrained growth and tumor progression may occur.


Author(s):  
E. Horvath ◽  
K. Kovacs ◽  
I. E. Stratmann ◽  
C. Ezrin

Surgically removed human pituitary glands as well as pituitary tumors fixed in glutaraldehyde, postfixed in osmium tetroxide, embedded in epon resin, stained with uranyl acetate and lead citrate have been investigated by electron microscopy in order to correlate ultrastructure with functional activity. In the course of this study two distinct types of microfilaments have been identified in the cytoplasm of adenohypophysiocytes.Type I microfilaments (Fig. 1) were found in the cytoplasm of anterior lobe cells of five female subjects with disseminated mammary cancer and two patients with severe diabetes mellitus. The breast cancer patients were treated pre-operatively for various periods of time with different doses of oxysteroids. The microfilaments had an average diameter of JO A, formed parallel bundles, were scattered irregularly in the cytoplasm and were frequently located in the perikaryon. They were not membrane-bound and failed to show any periodicity.


Author(s):  
Elif Gündoğdu ◽  
Uğur Toprak

Background: The middle ear cavity is ventilated through the aditus ad antrum. Aditus blockage contributes to the pathology of otitis media. Objective: To determine the normal values of the aditus ad antrum diameter on computed tomography and to investigate its relationship with chronic otitis media and related pathologies (tympanosclerosis and myringosclerosis). Methods: The temporal CT images of 162 individuals were evaluated retrospectively. In the axial sections, the inner diameter of the aditus was measured at the narrowest point at the cortex. The differences in diameter were compared between diseased and healthy ears. Results: In healthy individuals, the diameter was narrower in women. There was no difference between the right and left ears in healthy subjects. No correlation was found between age and diameter. In male patients with myringosclerosis, the diameter was slightly narrower on both sides but more marked on the left. In female patients with myringosclerosis, the diameter in both ears was slightly narrower. In cases of otitis media and tympanosclerosis, the diameter was less than that of healthy individuals, despite the lack of statistically significant result in all cases. Conclusion: The aditus ad antrum was narrower in diseased ears, indicating that a blocked aditus may contribute to the development of otitis media, as well as mucosal diseases.


1989 ◽  
Vol 68 (5) ◽  
pp. 869-872 ◽  
Author(s):  
L. J. DEFTOS ◽  
D. T. O’CONNOR ◽  
C. B. WILSON ◽  
P. A. FITZGERALD

2009 ◽  
Vol 55 (11) ◽  
pp. 1967-1976 ◽  
Author(s):  
Shiyun Huang ◽  
Honggang Li ◽  
Xiaofang Ding ◽  
Chengliang Xiong

Abstract Background: We recently detected cell-free seminal RNA (cfsRNA) and set out to study its concentration, integrity, stability in healthy individuals, and mechanisms for its protection from ribonucleases. Methods: We quantified cfsRNA by reverse-transcription quantitative real-time PCR (RT-qPCR) targeting of the 5′ region of the ACTB (actin, beta) transcript. cfsRNA integrity was analyzed by microcapillary electrophoresis and by amplification of full-length ACTB and DDX4 [DEAD (Asp-Glu-Ala-Asp) box polypeptide 4] transcripts, including measurement of the relative amounts of different regions of ACTB and DDX4 transcripts. Stability of cfsRNA was measured by time-course analysis of different regions of ACTB and DDX4 transcripts. To investigate whether cfsRNA was protected in complexed forms, we processed seminal plasma in 2 ways: filtration through pores of different sizes and Triton X-100 treatment before RNA recovery. Results: cfsRNA concentrations varied from 0.87–3.64 mg/L [mean (SD), 1.75 mg/L (0.92 mg/L)]. Most cfsRNA was present in partially degraded forms, with smaller amounts of middle and 3′ amplicons compared with 5′ amplicons. Although the 3′ region of the DDX4 transcript was degraded completely by 90 min, the 5′ regions of ACTB and DDX4 transcripts were stable up to 24 h. Filtration through 0.22-μm pores reduced ACTB and DDX4 mRNA concentrations by 72% and 61%, respectively. Nearly all seminal ACTB and DDX4 mRNA disappeared after Triton X-100 treatment. Conclusions: Although cfsRNA was partially degraded, it represented diverse transcript species and was abundant, fairly stable, and associated with particles in healthy individuals. cfsRNA may represent a potential noninvasive biomarker of the male reproductive system and of germline epigenetics.


1985 ◽  
Vol 61 (5) ◽  
pp. 571-580
Author(s):  
Kenji MIZUNO ◽  
Mitsuhiro GOTOH ◽  
Shigeatsu HASHIMOTO ◽  
Motoko OJIMA ◽  
Soitsu FUKUCHI

2010 ◽  
pp. P1-74-P1-74
Author(s):  
AJ Knox ◽  
M Xu ◽  
MG Edwards ◽  
BK Demasters ◽  
KO Lillehei ◽  
...  

2021 ◽  
Vol 1-2 (33-34) ◽  
pp. 14-18
Author(s):  
V. Skybchyk ◽  
◽  
O. Pylypiv ◽  

Context. It is known that in addition to transient ischemic attacks and insults, hypertension is often the cause of asymptomatic brain damage, including cognitive impairment (CI). Most of these studies show a positive relationship between midlife hypertension and cognitive decline at the advanced age. CI significantly affect the quality of life of patients, reduce the ability to learn, acquire new knowledge and skills, force them to change their usual way of life and often stop or reduce professional activities. Objective. To analyze the condition of cognitive functions in patients with stage 1 and stage 2 hypertension of 2nd-3rd degrees, with moderate and high cardiovascular risk and evaluate their gender peculiarities. Materials and methods. The study included 90 patients with stage 1 and stage 2 hypertension. The average age of patients with hypertension was 49.66 ± 8.74 years old. The average course of the disease was 7.7 ± 3.9 years. The comparison group consisted of 46 healthy individuals with normal blood pressure levels and without hypertension in anamnesis (the average age - 45.88 ± 3.03 years old). Applied methods included general clinical, methods of neuropsychological testing (MMSE, GPCOG, W. Schulte test), standard general clinical and biochemical laboratory methods (blood lipid spectrum, blood glucose, creatinine with GFR, electrolytes), instrumental (12-lead ECG, ambulatory monitoring of blood pressure, echocardiography in B-, D-modes), and statistical methods. Results. Patients with hypertension scored significantly less on the MMSE scale (26.82 ± 1.41 scores vs. 28.89 ± 0.82 scores, p = 0.001) and GPCOG (6.63 ± 1.88 scores vs. 8.35 ± 0.71 scores, p = 0.001) compared with healthy individuals and spent more time on performing Walter Schulte test (46.51 ± 8.59 seconds vs. 36.69 ± 6.77 seconds, p = 0.001). Moderate CI were detected in 36 patients (40.00 %) among the examined hypertensive patients; it means that the total score of MMSE was 24-26 scores (the norm is 27-30 scores). The total score on the MMSE scale was 25.47 ± 0.88 in hypertensive patients with CI and was significantly lower than in hypertensive patients without CI (р = 0.001). Cognitive functions in patients with CI were characterized by poorer indices of memory, counting and executive functions. It should be noted that the revealed changes had more reliable manifestations in male hypertensive patients. In particular, the total score on the MMSE scale was 26.57 ± 1.37, while in female ones it was 27.19 ± 1.41 scores (p = 0.04). CI on the MMSE scale were diagnosed in 43.4 % (n = 23) of male patients and in 35.1 % (n = 13) of female patients. The total score was also higher on the GPCOG scale in female patients - 6.89 ± 1.85 scores vs. 6.45 ± 1.89 scores, p = 0.26. Instead, the time to complete the tasks according to the Walter Schulte tables was longer in male patients - 47.74 ± 8.85 seconds vs. 47.73 ± 7.99 seconds, p = 0.10, respectively. The parameters of counting functions were significantly lower (p = 0.01) in the group of male hypertensive patients compared with female ones. Besides, men had lower indicators of short-term memory and orientation, women reproduced worse verbal material, but the difference was statistically insignificant (p-value more than 0.05). The sum of scores on the MMSE scale conversely correlated with male gender (r = -0.22, p = 0.03). The risk of low values of MMSE indices in male patients with hypertension was 42.00 % higher than in female ones (OR = 1.42 ± 0.32, with 95% CІ [0.18-2.65]). Conclusions. Hypertension is a significant independent risk factor for developing new cases of cognitive impairment. In particular, among the patients with stage 1 and stage 2 hypertension of 2nd-3rd degrees, with moderate and high cardiovascular risk, moderate cognitive impairment was revealed in 36 patients (40,00 %), the revealed changes were more manifested in male hypertensive patients.


2021 ◽  
Vol 20 (2) ◽  
pp. 37-44
Author(s):  
V. N. Zasimovich ◽  
V. V. Zinchuk ◽  
N. N. Ioskevich

Introduction. Reperfusion-reoxygenation syndrome (RRS) after revascularization of the lower limbs in obliterating atherosclerosis of the arteries is accompanied by a violation of the oxygen transport function of the blood (OTFB) and the content of gas transmitters (GTs). Reperfusion injury affects not only the tissues of the lower limbs, but also of anatomically distant organs, which supposes that effective RRS correction is required. Aim. To study the effect of Corvitin on the OTFB parameters and the content of GT of nitrogen monoxide (NO) and hydrogen sulfide (H2S) in the venous blood of the forearm after revascularization of the lower limb in chronic atherosclerotic occlusion of the superficial femoral artery (SFA). Materials and methods. The study included 118 male patients. Revascularization of the lower limb was carried out by the method of loop endaterectomy from the SFA. Patients of group I (n=52) received traditional medication, 51 patients of group II additionally received Corvitin. In the blood from the vein of the elbow bend before the operation, on the 3rd and 8th days after it, the indices of OTFB and GTs were determined. Results. In group I, on the 3rd day after surgery, pO2 increased in relation to healthy individuals by 5.2–18.5%, while pCO2 decreased by 4.8–6.7%, depending on the stage of initial ischemia. The concentrations of NO and H2S increased by 9.2–50.1% and 9.2–21.1%, respectively. The increase in the parameters of hyperoxemia, hypocapnemia and GT after the return of blood circulation decreases with the use of Corvitin (p˂0.05). By the end of the early postoperative period, the indicators of OTFB and GT not only return to their initial values, but also do not significantly differ from the group of healthy individuals (p˃0.05). Conclusion. The use of Corvitin effectively corrects violations of OTFB and GT during ischemia-reperfusion of the lower limbs, which prevents tissue reperfusion damage.


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