The expression of prostaglandins-related genes in erythrocytes of broiler chicken responds to thiram-induced tibial dyschondroplasia and recombinant glutathione-S-transferase A3 protein.

Tibial dyschondroplasia (TD) is a type of bone deformity found in fast-growing chickens, which induce inflammatory responses. Prostaglandins (PGs) implicate in bone formation and bone resorption, associated with inflammation in an autocrine/paracrine manner. This study used qRT-PCR and immunohistochemistry analysis to identify the expression patterns of PG-related genes in the erythrocytes of broiler chickens and explore the effects of thiram-induced TD and the recombinant glutathione-S-transferase A3 (rGSTA3) protein on the expression of PG-related genes: GSTA3, cyclooxygenase 2 (COX-2), prostaglandin D2 synthase (PTGDS), prostaglandin E synthase (PTGES), prostaglandin E2 receptor (PTGER) 3, PTGER4 and prostaglandin reductase 1 (PTGR1). Interestingly, the results showed that these seven PG-related genes expression was identified in the erythrocytes of broiler chicken, and thiram-induced TD suppressed the expression of these PG-related genes in the initial stage of TD and promoted their expression in TD recovery. These findings demonstrated that the immunoregulatory function of erythrocytes can be inhibited in the early stage of TD and promoted in the recovery stage by modulating the expression of PG-related genes. Further, the rGSTA3 protein can modulate the expression of PG-related genes in erythrocytes and participate in the recovery of TD.

Identification of apoptosis-related genes in erythrocytes of broiler chickens and their response to thiram-induced tibial dyschondroplasia and recombinant glutathione-S-transferase A3 protein.

Thiram, a carbamate pesticide, is known to induce tibial dyschondroplasia (TD) in broiler chickens. This study used a thiram-induced TD model to explore whether apoptosis-related genes were expressed in erythrocytes of broiler chickens and the impacts of thiram-induced TD and the recombinant GSTA3 protein in regulating these genes expression. In this study, mRNA and protein expression of six types of apoptosis-related genes (Bcl-2, Bax, Murine double minute MDM2, Bcl-2-associated athanogene BAG-1, BAG-3, STAT3) were identified in erythrocytes of broiler chickens by real-time PCR and immunohistochemistry, and we also found that thiram-induced TD induced the decreased expression of these antiapoptotic genes in the initial stage of TD and promoted their expression in TD recovery, which suggested that the expression of these apoptosis-related genes in erythrocytes is highly related to the development of TD. Further, the recombinant GSTA3 protein promoted the expression of all apoptosis-related genes in the initial stage of TD and recovered the normal expression of these genes in the recovery stage of TD, which indicated that the recombinant GSTA3 protein may participate in the recovery of TD. Further studies are needed to elucidate the mechanism of the response of erythrocytes to thiram-induced TD and the recombinant protein GSTA3 in broiler chickens.

[Correlation between C-MYC protein expression and genetic abnormalities in diffuse large B-cell lymphoma].

Objective: To study the correlation between expression of oncogene C-MYC protein and gene abnormality in diffuse large B-cell lymphoma (DLBCL). Methods: The expression of C-MYC protein and gene abnormality were detected by immunohistochemistry and fluorescence in situ hybridization (FISH), respectively, in 42 cases of paraffin-embedded DLBCL. All cases were collected at Department of Pathology, Weifang People's Hospital during January 2015 to October 2016. Results: The positive rate of C-MYC protein expression was 47.6% (20/42) and the rate of abnormal C-MYC gene by FISH was 26.2%(11/42), including translocation (23.8%, 10/42) and gene amplification (2.4%, 1/42). There was a close relationship between the protein expression and gene translocation (χ(2)=11.813; P=0.001) and gene translocation occurred primarily in GCB (χ(2)=4.029; P=0.045). Conclusion: The high expression (≥40%) of C-MYC protein is associated with its gene translocation, suggesting that C-MYC protein detection can be used as a surrogate marker for C-MYC gene translocation in DLBCL.

Mutations of transglutaminase-1 in Chinese patients with autosomal recessive congenital ichthyosis: a case report with clinical and genetic analysis of Chinese cases reported in literature.

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of diseases of keratinization, characterized primarily by abnormal skin scaling over the whole body surface. Recently, ARCI has been designated to include the major forms of lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE) and harlequin ichthyosis. The first two conditions are the most common major clinical subtypes, and both are caused principally by mutations in the transglutaminase 1 gene, TGM1, although other genes may be responsible in some cases. AIM: To identify the genetic mutations underlying LI in a Chinese family with LI, and to review all the known TGM1 mutations in Chinese patients with ARCI. METHODS: The proband had the severe classic LI phenotype, and was a member of a four-generation family with close blood relationships. We sequenced the DNA of the patients and close relatives. We also reviewed 13 Chinese patients with ARCI from 8 reported families, comprising 10 patients with LI, 2 with CIE and 1 with bathing suit ichthyosis. RESULTS: We characterized 14 different TGM1 mutations. Six of these were reported in other ethnic groups initially and later in Chinese patients, while the remaining eight were first described in Chinese patients. Of the latter, five have been reported only in Chinese patients, while the remaining three have also been reported in other ethnic groups. CONCLUSION: This study expands the current spectrum on TGM1 mutation and increases the knowledge of TGM1 mutation characteristics.

HES1 inhibits adipogenesis of porcine mesenchymal stem cells via transcriptional repression of FAD24.

Adipogenesis, the development from preadipocytes or mesenchymal stem cells (MSCs) to mature adipocytes, is regulated by a network of signaling pathways and transcription factors. The involvement of Notch signaling and its effector HES1 in adipogenesis has been investigated in several studies with conflicting results. The underlying mechanisms remain unclear because of the lack of information about HES1 target genes during adipocyte differentiation. As a novel gene transiently up-regulated in early adipogenesis, FAD24 functions as a positive regulator of adipocyte differentiation in both preadipocytes and MSCs. In the present study, we report that the expression level of FAD24 is inversely associated with that of HES1 in porcine MSCs after adipogenic induction. Enforced overexpression of HES1 in MSCs during the early stage of adipogenesis significantly repressed the transcription of FAD24 (P < 0.01) and the other pro-adipogenic genes (P < 0.05), resulting in reduced intracellular lipid accumulation. Sequence analysis showed that porcine FAD24 harbors an evolutionarily conserved HES1 binding site in its proximal promoter region. Functional HES1, but not its dominant-negative mutant, markedly reduced the promoter activity of FAD24 (P < 0.01). Site-directed mutation and chromatin immunoprecipitation further confirmed that HES1 inhibits FAD24 transcription by direct binding to the promoter. Taken together, we identified FAD24 as a novel downstream target of HES1 during adipogenesis. Our data suggest that HES1-mediated repression of FAD24 transcription at the early stage of adipocyte differentiation may contribute to the impaired adipogenesis induced by the Notch-HES1 signaling pathway.

A novel allele, HLA-A*11:01:10, identified by sequence-based typing in a Chinese individual.

The novel allele human leukocyte antigen (HLA)-A*11:01: 10 differs from HLA-A*11:01:10 by a synonymous nucleotide exchange at codon 146 in exon 2 (G/A). Here, we describe the identification of the novel allele HLA-A*11:01:10, which has been detected in a registered donor of the China Marrow Donor Program. The complete HLA typing results were as follows: A*02:01, *11:01:10; B*15:11, *15:18; C*03:03, *08:01; DRB1*08:02, *15:01.

[An observation of the secretion of growth hormone and contraction of gall bladder after long-term use of growth-inhibition excitants].

We sought to examine the feasibility of intermittent dosing of octreotide in acromegalics to avoid the well-documented side effect of cholelithiasis. In fourteen acromegalic patients, we measured serum GH, five hour GH profile (mean GH, measured hourly 8:00 am to 12:00 pm) prior to the discontinuation of octreotide and weekly thereafter. In addition, gallbladder contractility was quantitated using the percent of relative gallbladder contractility (PRGC) obtained by ultrasound during a fat meal test. One week after withdrawal of octreotide, basal GH and five our GH profile (14.6 +/- 3.3 micrograms/L, 13.4 +/- 3.2 micrograms/L, respectively) were significantly less than (P < 0.01, P < 0.05), and represented 36% and 24% of their respective pretreatment values. At the end of two weeks, these parameters were 60% and 56% of their pretreatment levels. We also measured serum octreotide levels following withdrawal; the drug is completely eliminated from the serum within 3 day. In all of 6 patients who did not develop stones, PRGC normalized within one week. In 8 patients who developed stones, 3 of them had restoration of normal contractility in 2 weeks. Our results show that upon withdrawal of octreotide, gall bladder contractility normalizes while GH suppression persists for a longer period of time. Therefore, intermittent therapy may allow clearance of stagnated bile and hence decrease the incidence of cholelithiasis in acromegalic patients receiving long term octreotide therapy.

Prevalence of growth hormone deficiency of children in Beijing.

103,753 (male 51,994, female 51,759) primary and middle school students aged 6-15 years in two districts in Beijing city were surveyed from October 1987 to April 1989. The heights of the students were measured. According to the height standard of northern cities in China, 202 students with heights below the 3rd percentile for age were requested for detailed history, physical examination, screening GH test bone age, T4, SGPT, chest X-ray, routine urine test and sex chromatin (in female). If GH less than 10 micrograms/L, two provocative tests (L-dopa or clonidine and insulin hypoglycaemia test) were done. Then the heights of the short students were observed for 1/2-2 years. GHD was diagnosed in 12 cases based on the GH peak levels less than 10 micrograms/L in two provocative tests, whose growth velocity was slower than that for students of the same age and sex. Of these subjects with GHD, total GHD (GH less than 5 micrograms/L) was present in 7 and partial GHD (GH = 5-9.9 micrograms/L) in 5. The 12 GHD students (male 9, female 3) aged 8.9-15.7 years accounted for 1/8,646 in the total surveyed students. The male and female GHD accounted for 1/5,777 and 1/17,253 in the total males and females respectively.

PIP: The prevalence of growth hormone (GH) deficiency in Beijing children was estimated by measuring the heights of 103,753 children aged 6-15 and assessing those below the 3rd percentile in height. The following data were collected from 202 students: history, physical examination results, bone age, T4, chest x-ray, liver function tests, urinalysis, and sex chromatin in the girls who had not menstruated. 13 short children were excluded because of organic disease. Those with GH 10 mcg/L were subjected to provocative tests using L-dopa, clonidine, and insulin. GH deficiency was diagnosed in 12 children based on GH levels, provocative testing, and growth velocity over the next 1.5 years. There was total GH deficiency (GH 5 mcg/L) in 7 children and partial GH deficiency (GH 5-9.5 mcg/L) in 5 others. These 9 boys and 3 girls accounted for 1 case of GH deficiency/8646 middle school students in Beijing. The prevalence is between that published for Newcastle and Edinburgh, UK. This information will be useful for estimating the amount of synthetic GH needed in China.

A preliminary study of radioimmunoimaging by 131I-COC183B2 monoclonal antibody in patients with epithelial ovarian cancer.

Monoclonal antibody 131I-COC183B2, developed in our laboratory and proved to fit for human treatment was injected intraperitoneally or subcutaneously in 13 patients. In 8 cases with i.p. injection the disease corresponded with the image, i.e. 3 primary ovarian epithelial cancers showed positive images, 1 ovarian Krukenberg tumor was negative and the other 4 negative images included 1 uterine myoma and 3 ovarian teratomas. In the subcutaneous injection group, 4 cases had ovarian carcinoma, surgery and chemotherapy. Two negative images corresponded with the clinical status-in good health, another negative case had metastatic left supraclavicular lymph node due to ovarian mucinous adenocarcinoma. The last negative image in this group was a case of benign ovarian teratoma which was proved after surgery. The 1 positive case was waiting to be proved by a scheduled third operation. The computer scintigram calculation of T/NT was 5.35 to 13.7. The results suggest that this monoclonal antibody can be used for radioimmunoimaging for the localization of ovarian carcinoma, which is not only helpful for clinical staging and differential diagnosis but is also a good follow-up method.

[Evaluation of adult idiopathic growth hormone deficiency with other pituitary hormones deficiency].

The type and percentage of multiple pituitary hormone deficiency (MPHD) were studied in 42 patients with idiopathic growth hormone deficiency (IGHD). It was found that the development of secondary sexual characteristics was poor or absent in 39 patients (93%) with gonadotropin deficiency (GnD). Mean serum testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the 39 patients were significantly less than those of normal adult males (P less than 0.01). Mean testicular volume in 36 patients with GnD was significantly less than that in 3 with normal T level. We also found that 24-hour urinary free cortisol level (24 hour UFC) was low in 24 (57.1%) of 42 patients, but it is important that none had obvious symptoms of hypoadrenocorticism such as hypoglycemia, hypotension etc and received adrenal-corticosteroid treatment. 22 (52.4%) of the 42 patients suffered from hypothyroidism, with serum thyroxine (T4) level lower than normal but thyrotrophin (TSH) within normal range. 6 patients with hypothyroidism had moderate symptoms such as cold intolerance, constipation, rough and dry skin, slowing down both mentally and physically. 17 patients have treated with thyroxine. From the results mentioned above, 14 of the 41 patients with MPHD had pan-pituitary hormones (LH, FSH, TSH, ACTH) deficiency, only one had isolated growth hormone deficiency. Among all the patients, 23 underwent breech delivery and 11 patients had birth asphyxia. We therefore conclude that: (1) most of the IGHD cases are complicated with other pituitary hormone deficiency; (2) most of the IGHD cases have with MPHD; (3) Breech delivery and birth asphyxia were important etiological factors of IGHD.

[Application of the assays for progesterone and estradiol in saliva in family planning research].

PIP: A clinical study has been conducted on the radioimmuno assays of progesterone and estradiol in saliva to analyze the effect of norethindrone visiting pills and levonorgestrel post coital contraceptives on ovarian function and to monitor the resumption of ovarian function after the termination of early pregnancy using sulprostone. Two cases were recruited for the study of norethindrone, 5 cases for the study of levonorgestrel, and 4 cases for sulprostone. The studies showed that the levels of the 2 steroids in saliva were correlated with those observed in serum. The determination of the hormone level in saliva after termination of pregnancy using sulprostone provided information on the length of time between abortion and resumption of ovarian function. Analysis of hormones in saliva is a useful and convenient procedure in family planning research. Since the concentration of hormone in saliva is much lower than in serum, highly sensitive assays are needed, and more samples have to be collected due to the large variance of hormone levels in saliva.^ieng

[Comparison of changes of serum gonadotropins and steroid hormones in azoospermic men caused by gossypol and other factors].

PIP: The plasma FSH, LH, PRL, T, E2, and F levels were compared in normal men (group 1), azoospermic men with different etiologies including gossypol treatment (group 2), men with uncertain diagnoses (group 3), and men with Klinefelter's syndrome (group 4) in order to determine whether differences in hormonal changes and their extent could be discerned in affected subjects. Results show that the average FSH and LH levels in azoospermic men as a whole group (n=50) were significantly higher than those in normal men (P0.001). There was no significant difference in PRL, T, E2, and F levels from the control group (P0.05). It was interesting to note the extent to which hormone changes were observed in different groups of affected subjects. Normal FSH levels were found in groups 2 and 3 in 50% of the patients while FSH levels in the rest of the patients were markedly higher (P0.001). The changes in serum LH levels were parallel with FSH levels in groups 3 and 4; in group 2, both LH and T/LH ratio remained unchanged but T, E2, and F levels were elevated while PRL decreased significantly. Patients in groups 3 and 4 have shown a very low T and T/LH ratio when compared with the control group and group 2 (P0.001). It was concluded that the contraceptive dose of gossypol did not cause obvious damage in Leydig cell function in terms of T production. High FSH levels indicated the severe damage in germinal epithelium of the testis. In order to minimize side effects and to avoid irreversibility in spermatogenesis, the minimal effective dose of gossypol must be used as a contraceptive. Some objective reference parameters were recommended to monitor the contraceptive dosage of gossypol. (author's modified)^ieng