[Bioinformatics-based analysis of the effect of general Transcription Factor IIH on prognosis of Prostate cancer].

Objective: To investigate the genetic and expression characteristics of transcription factor IIH (TFIIH) in pre-initiationcomplex in prostate cancer (PCa) and its relationship with prostate cancer progression. Methods: Analyzing the expression characteristics and clinical signification of TFIIH subunits about 495 cases of PCa and 52 cases of adjacent cancer in The Cancer Genome Atlas-Prostate adenocarcinoma (TCGA-PRAD) database. PCa microarray chip was used to verify the correlation between the key factor General Transcription Factor IIH Subunit 4 (GTF2H4) in TFIIH and clinical features. Results: The 495 patients with PCa were (61.01±6.82) years old.The mRNA expression of ERCC3、GTF2H4 and MNAT1 were high in PCa tissues with GS≥8(P<0.05). The expression of GTF2H4 and MNAT1 were relevant to the pathological stages(P<0.05). High expression of GTF2H4 has higher biochemical recurrence (BCR) rate in PCa patients(HR=2.47, 95%CI:1.62-3.77, P<0.001), which has better predictive effect of BCR in PCa patients(The 3rd, 5th, and 7th year AUC all>0.7) than other subunits, and it has been verified in four additional databases. Single-factor Cox regression analysis showed that GTF2H4 were risk factors for BCR (HR=2.470, 95%CI:1.620-3.767, P<0.001) and GTF2H5 were protective factors(HR=0.506,95%CI: 0.336-0.762, P=0.001). The results of immunohistochemical staining showed that the protein expression of GTF2H4 was correlated with the clinical features of PCa patients.The differences of the above results were statistically significant. Conclusion: GTF2H4, the key factor of TFIIH, is highly expressed in PCa and indicates a poor prognosis.

[The characteristics of gut microbiota in type 2 diabetes mellitus patients with hypertriglyceridemia].

Objective: To investigate the characteristics of gut microbiota in type 2 diabetes mellitus (T2DM) patients with hypertriglyceridemia (HTG). Methods: Eighty-one patients first diagnosed with T2DM were enrolled in the Third Xiangya Hospital of Central South University from January 2018 to December 2020, including 58 patients [46 males and 12 females, aged (43±13) years] with HTG [HTG group, triglyceride (TG)≥1.7 mmol/L]. There were 23 cases without HTG (NTG group), including 20 males and 3 females, aged (46±13) years. According to the severity of HTG, the patients of HTG group were divided into severe HTG group (STG group, TG ≥5.6 mmol/L) and mild HTG group (MTG group, 1.7 mmol/L≤TG<5.6 mmol/L). Thirty healthy controls were matched accordingly, including 21 males and 9 females, aged (45±6) years. Clinical laboratory indicators and feces of the subjects were collected and 16S rRNA sequencing was performed to compare the differences in intestinal flora among the groups. Results: The Shannon and Simpson indexes in HTG group were lower than those in NTG group and healthy control group (5.02±0.91 vs 5.45±0.55 and 5.60±0.63, P=0.003; 0.90±0.06 vs 0.93±0.04, 0.94±0.04, P=0.002). Compared with healthy control group and NTG group, the abundance of intestinal P_Proteobacteria, g_Escherichia_Shigella, s_Escherichia_Coli and g_Clostridium_sensu_stricto_1 increased in HTG group, while the abundance of p_Firmicutes, g_Faecalibacterium and Faecalibacterium_prausnitzii decreased. The abundance of g_Clostridium_sensu_stricto_1 in the STG group was higher than that of NTG and MTG groups, while the abundance of g_Faecalibacterium decreased. Spearman correlation analysis suggested that g_Clostridium_sensu_stricto_1 was positively correlated with glycosylated hemoglobin (r=0.22, P=0.044), fasting blood glucose (r=0.36, P=0.001), TG (r=0.27, P=0.015) and total cholesterol (r=0.44, P<0.001). Logistic regression analysis indicated that g_Faecalibacterium was a protective factor for T2DM with HTG(OR=0.90, 95%CI:0.83-0.97, P=0.006). Conclusions: The intestinal flora of T2DM patients with HTG was dysregulated, which was manifested as decreased diversity, increased abundance of P_Proteobacteria and decreased abundance of p_Firmicutes. g_Faecalibacterium is a protective factor for T2DM with HTG.

The antibiofilm and collagen-stabilizing effects of proanthocyanidin as an auxiliary endodontic irrigant.

AIM: To evaluate the antibiofilm effect of proanthocyanidin (PA) solution as an irrigant against Enterococcus faecalis (E. faecalis) and its influence on the mechanical properties and biodegradation resistance of demineralized root dentine. METHODOLOGY: Enterococcus faecalis were introduced into human root dentine tubules by a serial centrifugation method and grown for 1 week. Dentine blocks infected with 1-week-old E. faecalis biofilms were treated with the following irrigants: sterile water (control), 2% chlorhexidine (CHX), 2% PA, 5% PA and 10% PA. After treatment, the live and dead bacteria proportions within E. faecalis biofilms were analysed using confocal laser scanning microscopy. To evaluate the biostability of fully demineralized dentine treated by the aforementioned irrigants, the elastic modulus and hydroxyproline release of human dentine incubated in collagenase solution were tested at baseline, after irrigant treatment and after biodegradation, respectively. Furthermore, the surface chemical bond of demineralized dentine collagen treated by various irrigants was characterized by X-ray photoelectron spectroscopy (XPS). Statistical analysis was performed using one-way anova and Tukey's post hoc multiple comparisons with the significance level at 5%. RESULTS: The proportion of dead E. faecalis volume was significantly higher in the PA and CHX groups than that in the control group (P < 0.05). PA irrigation significantly increased the mechanical properties of demineralized dentine (P < 0.05), and the effect was enhanced with increasing PA concentration. CHX and PA groups had significantly less elasticity loss and hydroxyproline release (P < 0.05). The biomodification of dentine collagen by PA was verified by increased C-O/C-N peak percentage under C1s and C-O peak percentage under O1s narrow-scan XPS spectra. CONCLUSIONS: Proanthocyanidin killed E. faecalis within biofilms and enhanced the biostability of the collagen matrix of demineralized root dentine. It might be used as an auxiliary endodontic irrigant with antibiofilm and collagen-stabilizing effects.

[The role of cell-crystal reaction mediated inflammation in the formation of intrarenal calcium oxalate crystals].

Calcium oxalate nephrolithiasis is the common disease of urinary surgery, its exact pathogenesis is still unclear.It is believed that the renal inflammatory injury induced by cell-crystal reaction plays an important role in the formation of intrarenal calcium oxalate crystals. Recent studies indicated that inflammation induced by cell-crystal reaction can cause renal cell damage, stimulate intracellular expression of NADPH oxidase, trigger the massive production of reactive oxygen species, activate nuclear factor-κB signaling pathway, release a large number of inflammatory factors, and cause inflammatory cascade effect of the kidney, thus promoting the accumulation, nucleation and growth of calcium salt crystals, eventually leading to the formation of intrarenal crystals and even stones. In this process, the regulatory factors and mechanisms involved include macrophages, NLRP3-high mobility group box-1 protein inflammation network, fetuin A, autophagy activation and other factors.

Bacterial communities associated with invasive populations of Bactrocera dorsalis (Diptera: Tephritidae) in China.

The oriental fruit fly Bactrocera dorsalis (Hendel) is a destructive insect pest of a wide range of fruits and vegetables. This pest is an invasive species and is currently distributed in some provinces of China. To recover the symbiotic bacteria of B. dorsalis from different invasion regions in China, we researched the bacterial diversity of this fruit fly among one laboratory colony (Guangdong, China) and 15 wild populations (14 sites in China and one site in Thailand) using DNA-based approaches. The construction of 16S rRNA gene libraries allowed the identification of 24 operational taxonomic units of associated bacteria at the 3% distance level, and these were affiliated with 3 phyla, 5 families, and 13 genera. The higher bacterial diversity was recovered in wild populations compared with the laboratory colony and in samples from early term invasion regions compared with samples from late term invasion regions. Moreover, Klebsiella pneumoniae and Providencia sp. were two of the most frequently recovered bacteria, present in flies collected from three different regions in China where B. dorsalis is invasive. This study for the first time provides a systemic investigation of the symbiotic bacteria of B. dorsalis from different invasion regions in China.

[Clinical analysis of liver transplantation in treatment of liver metastatic cancer].

OBJECTIVE: To evaluate the feasibility and outcome of liver transplantation in the treatment of liver metastatic cancer. METHODS: Four patients with pathologically confirmed liver metastatic cancer underwent liver transplantation, including one of liver metastases from pancreatic endocrine tumor, one from rectal endocrine tumor, one from stomach stromal tumor and one from colorectal carcinoma. Classic surgical method was adopted, i. e. orthotopic liver transplantation for the recipients and transplants came from cadaveric donors. RESULTS: All the four patients had a smooth operation, an uneventful early postoperative recovery and good living quality. The patient with liver metastases from pancreatic endocrine tumor had liver tumor recurrence at four and a half years after the transplantation, and then underwent left lateral hepatic lobectomy, without any recurrence until now. The patient with liver metastases from rectal endocrine tumor had right renal and pelvic tumor metastasis at 16 months after the operation, and died of tumor recurrence 5 years after the liver transplantation. The patient with liver metastases from gastric stromal tumor had extensive pelvic metastases at five and a half months after the transplantation, and survived with tumor for 4 years and 6 months after the operation. The patient with liver metastases from colorectal carcinoma had extensive bilateral lung metastases at 3 months after the transplantation and died one and a half years after the operation. CONCLUSION: For well-differentiated unresectable metastatic liver cancers, liver transplantation may serve as a treatment option and better treatment results can be achieved for some highly selected patients.

[Liver transplantation for benign liver tumor: six cases report and literature review].

OBJECTIVE: To analyse and explore the indications and efficacy of liver transplantation for benign liver tumor. METHODS: From Jan.2001 to Dec.2014, 6 patients, incluing 3 males and 3 females, with benign liver tumor underwent liver transplantation in our department.There were 2 cases of hepatic epithelioid hemangioendothelioma, 1 case of hepatic cavernous hemangioma, 1 case of liver mesenchymal hamartoma, 1 case of hilar bile duct mucinous cystadenoma, and 1 case of hepatic adenoma. The data of surgical procedure, perioperative complications, postoperative management, and the outcome of follow-up were analyzed. RESULTS: Six orthotopic liver transplantation from one living donor and five cadaveric donors were performed. One patient died in the perioperative period, and other patients were discharged with normal liver and kidney function. Within the follow-up time of 22 to 88 months, these patients could live the normal lives with stable graft function and nutritional status. CONCLUSIONS: Liver transplantation is the most efficient treatment for unresectable and symptomatic benign lesions, with the favourable outcome.

Rapid diagnosis of the economically important fruit fly, Bactrocera correcta (Diptera: Tephritidae) based on a species-specific barcoding cytochrome oxidase I marker.

The guava fruit fly, Bactrocera correcta (Bezzi) (Diptera: Tephritidae), is an invasive pest of fruit and vegetable crops that primarily inhabits Southeast Asia and which has the potential to become a major threat within both the Oriental and Australian oceanic regions as well as California and Florida. In light of the threat posed, it is important to develop a rapid, accurate and reliable method to identify B. correcta in quarantine work in order to provide an early warning to prevent its widespread invasion. In the present study, we describe a species-specific polymerase chain reaction assay for the diagnosis of B. correcta using mitochondrial DNA cytochrome oxidase I (mtDNA COI) barcoding genes. A B. correcta-specific primer pair was designed according to variations in the mtDNA COI barcode sequences among 14 fruit fly species. The specificity and sensitivity of the B. correcta-specific primer pair was tested based on the presence or absence of a band in the gel profile. A pair of species-specific B. correcta primers was successfully designed and named BCOR-F/BCOR-R. An ∼280 bp fragment was amplified from specimens belonging to 17 geographical populations and four life stages of B. correcta, while no such diagnostic bands were present in any of the 14 other related fruit fly species examined. Sensitivity test results demonstrated that successful amplification can be obtained with as little as 1 ng µl⁻¹ of template DNA. The species-specific PCR analysis was able to successfully diagnose B. correcta, even in immature life stages, and from adult body parts. This method proved to be a robust single-step molecular technique for the diagnosis of B. correcta with respect to potential plant quarantine.

[Analysis on drug sensitivity spectrum of 167 multidrug-resistant Mycobacterium tuberculosis in China].

Objective: To investigate the drugs-sensitivity spectrum of multidrug-resistant tuberculosis (MDR-TB) in China and provide a scientific evidence for the drug selection in clinical therapy and the control of MDR-TB. Methods: A total of 167 strains of MDR-TB were included in this study. Every strain was genotyped by lysX gene sequencing and their sensitivity to 13 different anti-TB drugs was tested by using MicroDST(TM) and BACTEC(TM) MGIT 960(TM) liquid-culturing method. The association between drug resistance and genotypes as well as cross drug resistance was also analyzed. The results were analyzed by means of the comparison of enumeration data between two groups with χ(2) test. Results: The overall resistance rate of 167 MDR-TB strains to 11 anti-TB drugs, except isoniazide and rifampicin, was 95.81%, the rates of pre-extensive drug-resistance (pre-XDR) and extensive drug-resistance were 31.14%(52/167) and 6.59% (11/167), respectively. The streptomycin resistance rate of Beijing genotypes was significantly higher than that of the non-Beijing genotypes ( χ(2)=30.682, P<0.05), while the pre-XDR proportion in Beijing genotypes was lower than that in non-Beijing genotypes (χ(2)=5.332, P<0.05). The resistance rates of Ofloxacin and Pyrazinamide in the modern Beijing genotype were significantly higher than those in classical ones (χ(2)=4.105 and χ(2)=3.912, P<0.05). In addition, the cross-resistance rate to rifampicin and rifabutin was 86.23%. A significant difference in drug-resistance rate to rifabutin was seen among groups with different levels of rifampicin resistance (χ(2)=45.912, P<0.05). There was positive correlation not only between ofloxac resistance and moxifloxac resistance, but also between amikacin resistance and kanamycin resistance, with the coefficient of 0.87 and 0.91, respectively. Conclusions: In this study, we observed that there were high incidences of the resistance to 11 anti-TB drugs in 167 clinical MDR-TB strains and the cross resistance phenomena between drugs of the same type were quite serious. The majority of MDR-TB strains belonged to Beijing genotype, which was highly associated with streptomycin resistance.

Protective Effect of a Novel Technique for Liver Transplantation in the Rat.

The rat orthotopic liver transplantation model with extremely short anhepatic phase was established to study its protective effect on the recipients and graft. One hundred fifty adult male Wistar rats were randomly divided into three groups: group A (n = 30), using magnetic rings for the suprahepatic vena cava reconstruction; group B (n = 30), using 7/0 Prolene sutures for suprahepatic vena cava running anastomosis as control; and a sham-operated group (n = 30) as a blank control group. The changes in liver enzyme, serum creatinine, endotoxin, and cytokine levels and histopathology were recorded. The serum creatinine, potassium, alanine transaminase, and alkaline phosphatase levels at different points in time in group A were lower than those in group B (P < .05). The level of portal vein blood endotoxin in group A was significantly lower than that in group B at each point (P < .01). At the same time, all the cytokines in group B were higher than those in group A, and the two groups were higher than those in the sham operation group. The mean levels of tumor necrosis factor-α (TNF-α), interferon-γ, (IFN-γ), and interleukin-1ß (IL-1ß) at 3 hours were higher than at 6 hours in group A. IL-10 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were all higher at 3 hours in groups A and B. Levels of monocyte chemotactic protein-1, L-selectin, and TIMP-1 in group A and IL-10, monocyte chemotactic protein-1, L-selectin, and TIMP-1 in group B were higher in blood than in the liver. Levels of TNF-α, IFN-γ, IL-1, IL-10, and intracellular adhesion molecule-1 in group A and TNF-α, IFN-γ IL-1ß, and intracellular adhesion molecule-1 in group B were higher in the liver than in blood. We conclude that the extremely short anhepatic phase has protective effects on recipients and grafts in rat liver transplantation because it is related to alleviating ischemia-reperfusion injury and reducing the endotoxin release.

Proline in a transmembrane helix compensates for cavities in the photosynthetic reaction center.

A site-specific double mutant, in which the large aromatic residues M208Tyr and L181Phe in the interior of the photosynthetic reaction center (RC) complex were replaced by smaller threonine residues, showed a dramatic reduction in the number of assembled complexes and was incapable of photosynthetic growth. The cavity created by the smaller side-chains was thought to interfere with the stability and/or assembly of the complex. Phenotypic revertants were recovered in which a spontaneous second-site mutation restored photocompetence in the presence of the original site-specific mutations. In these strains, an Ala-->Pro substitution in a neighboring transmembrane helix (at M271) resulted in an increased yield of RC complexes. To test the hypothesis that the original phenotype was due to a cavity, other mutants were constructed that created similar-sized voids at other positions in the membrane-spanning interior. These substitutions caused the same phenotype. Coupling of the above proline substitution to these new cavity mutants also resulted in photocompetent strains that carry increased levels of RC complexes. Therefore, the proline substitution at M271 serves as a global suppressor of the phenotype caused by these internal cavities. The proline substitution slightly increases the thermal stability of the complex at higher temperatures, but the mutant and suppressor strains have about the same stability at the optimal culture temperature, where both are less stable than the wild-type strain. Therefore, the proline substitution may suppress the non-photosynthetic phenotype of cavity mutants by facilitating folding of the nascent polypeptides as they assemble with cofactors to form the transmembranar RC complex. The proline replacement occurs at a pre-existing kink in a transmembrane helix where it can be accommodated without introducing a strain in the structure. The function of proline residues in transmembrane helices might be to promote folding and/or assembly in general.

Milan criteria, University of California, San Francisco, criteria, and model for end-stage liver disease score as predictors of salvage liver transplantation.

The selection criteria for salvage liver transplantation (SLT) candidates have not been previously established. A global analysis for the association between the criteria and prognosis is required. All of the adult patients who underwent liver transplantation with a diagnosis of hepatocellular carcinoma (HCC) from January 1, 2000, to December 31, 2011, were retrospectively analyzed. A total of 1,554 cases were involved, including 1,392 primary liver transplantation (PLT) and 162 SLT cases. All the cases were classified into 3 groups according to the Milan criteria combined with the University of California, San Francisco (UCSF), criteria, and significant differences were found between the 2 groups. The overall graft survival rate was lower in all cases of SLT than in PLT (P = .030). Within the Milan criteria, no significant difference in the graft survival rate was found between PLT and SLT. In a Cox regression analysis, the Model for End-Stage Liver Disease (MELD) score and tumor levels graded according to the Milan/UCSF criteria were found to be independent risk factors for the graft survival rate. Receiver operating characteristic (ROC) curves were generated by the fatality risk values calculated by means of the Cox model and the 1-year graft survival rates of all the patients and of the SLT patients. The areas under the ROC curves were 0.922 and 0.935, respectively. Compared with PLT, the global graft survival rate of SLT was compromised. The MELD score and Milan/UCSF criteria were effective in predicting the prognosis of PLT and SLT. Therefore, when the recurrent lesions of HCC are within the Milan criteria, SLT can be performed with a good prognosis.

MiR-216b is involved in pathogenesis and progression of hepatocellular carcinoma through HBx-miR-216b-IGF2BP2 signaling pathway.

This study aims to investigate the expression status of miRNA-216b in familial hepatocellular carcinoma (HCC) and the correlation between miRNA-216b expression and pathogenesis, as well as the progression of HCC. The expression profile of miRNAs in plasma of peripheral blood between HCC patients with HCC family history and healthy volunteers without HCC family history was determined by microarray. Using real-time quantitative PCR to detect the expression in paired tissues from 150 patients with HCC, miR-216b was selected as its expression value in HCC patients was significantly lower compared with healthy volunteers. Next, miR-216b expression and the clinicopathological features of HCC were evaluated. The effect of miR-216b expression on tumor cells was investigated by regulating miR-216b expression in SMMC-7721 and HepG2 in vitro and in vivo. Finally, we explored mRNA targets of miR-216b. In 150 HCC, 37 (75%) tumors showed reduced miR-216b expression comparing with their adjacent liver tissues. The decreased expression of miR-216b was significantly correlated with tumor volume (P=0.044), HBV infection (P=0.026), HBV DNA quantitative (P=0.001) and vascular invasion (P=0.032). The 5-year disease-free survival and overall rates after liver resection in low expression and high expression groups of miR-216b are 62% and 54%, 25% and 20%, respectively. MiR-216b overexpression inhibited cell proliferation, migration and invasion, and miR-216b inhibition did the opposite. The expression of hepatitis B virus x protein (HBx) has tight correlation with downregulation of miR-216b. Furthermore, miR-216b downregulated the expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and exerted its tumor-suppressor function through inhibition of protein kinase B and extracellular signal-regulated kinase signaling downstream of IGF2. MiR-216b inhibits cell proliferation, migration and invasion of HCC by regulating IGF2BP2 and it is regulated by HBx.

Recombinant immunoglobulin variable domains generated from synthetic genes provide a system for in vitro characterization of light-chain amyloid proteins.

The primary structural features that render human monoclonal light chains amyloidogenic are presently unknown. To gain further insight into the physical and biochemical factors that result in the pathologic deposition of these proteins as amyloid fibrils, we have selected for detailed study three closely homologous protein products of the light-chain variable-region single-gene family VkIV. Two of these proteins, REC and SMA, formed amyloid fibrils in vivo. The third protein, LEN, was excreted by the patient at levels of 50 g/day with no indication of amyloid deposits. Sequences of amyloidogenic proteins REC and SMA differed from the sequence of the nonpathogenic protein LEN at 14 and 8 amino acid positions, respectively, and these amino acid differences have been analyzed in terms of the three-dimensional structure of the LEN dimer. To provide a replenishable source of these human proteins, we constructed synthetic genes coding for the REC, SMA, and LEN variable domains and expressed these genes in Escherichia coli. Immunochemical and biophysical comparisons demonstrated that the recombinant VkIV products have tertiary structural features comparable to those of the patient-derived proteins. This well-defined set of three clinically characterized human kIV light chains, together with the capability to produce these kIV proteins recombinantly, provide a system for biophysical and structural comparisons of two different amyloidogenic light-chain proteins and a nonamyloidogenic protein of the same subgroup. This work lays the foundation for future investigations of the structural basis of light-chain amyloidogenicity.

Endogenous formaldehyde as a potential factor of vulnerability of atherosclerosis: involvement of semicarbazide-sensitive amine oxidase-mediated methylamine turnover.

The mouse is known to be highly resistant to atherosclerosis. However, some inbred mouse strains are vulnerable to atherosclerosis when they are fed a high-cholesterol, high-fat diet. Increased deamination of methylamine (MA) and the subsequent production of formaldehyde has been recently shown to be a potential risk factor of atherosclerosis. In the present study semicarbazide-sensitive amine oxidase (SSAO)-mediated MA turnover in C57BL/6 mouse, a strain very susceptible to atherosclerosis, has been assessed in comparison to a moderate, i.e. BALB/c, and resistant, i.e. CD1, mouse strains. Kidney and aorta SSAO activities were found to be significantly increased in C57BL/6 in comparison to BALB/c and CD1 mice. A significant increase of urinary MA and formaldehyde were detected in C57BL/6. [14C]MA following intravenous injection would be quickly metabolized by SSAO. The labeled formaldehyde product would cross link with proteins. C57BL/6 exhibits significantly higher labeled protein adducts than BALB/c and CD1 in response to [14C]MA. The results indicated that mice vulnerable to atherosclerosis possess an increased SSAO-mediated MA turnover. The increase of production of formaldehyde, possibly other aldehydes, may induce endothelial injury or be chronically involved in protein cross-linking and subsequent angiopathy.

Excessive production of insulin-like growth factor-I by silicotic rat alveolar macrophages.

The supernatant of silicotic rat alveolar macrophages can stimulate fibroblast growth. The present study demonstrates that this activity is mainly attributed to insulin-like growth factor-I. Partial purification of the supernatant of alveolar macrophages, which were from silica-exposed 5 to 6-week-old rats, revealed a protein peak (peak 5) eluted from a molecular-sieve HPLC column, corresponding to a MW of 6-9 kDa. Activity assay and radioimmunoassay indicated that this peak is more potent with regard to stimulation of fibroblast growth and has higher insulin-like growth factor-I immunoreactivity, but there was no detectable activity of interleukin-1 or tumor necrosis factor. Quantification of insulin-like growth factor-I also manifests elevated insulin-like growth factor-I levels in silicotic rat bronchoalveolar lavage fluids which tend to increase with prolongation of silica exposure in vivo, but no alteration in insulin-like growth factor-I level can be found in sera. These findings suggest that excessive production of insulin-like growth factor-I by alveolar macrophages locally may play a pivotal role in silica-induced pulmonary interstitial fibrosis.

Effects of high-energy shock waves on testes of Wistar rats.

The effects of high-energy shock wave (HESW) on testes are still unknown. We investigated Wistar rats at 3 months of age for morphologic and functional changes in the testes and in serum follicle-stimulating hormone (FSH), progesterone (Prog), and testosterone (T). In an initial study, 12 rats received 1000 shocks at 19 kV directed at their testes using the JDPN-IV lithotripter. Two animals were sacrificed, and their testes were step-sectioned for light and electron microscopic examination on the operation day and on postoperation days one, two, four, eight, and sixty. There was angiectasis and congestion (58%) and focal hemorrhage (42%) in the testicular tissue, as well as mitochondrial swelling, reduction or disappearance of mitochondrial cristae (42%), and degranulation of the rough endoplasmic reticulum (33%) in spermatocytes. In the definitive study, groups of 10 rats were exposed to the same power index directed at their testes. One week after this exposure in Group 1 and at 3 and 6 weeks in Group 2, the animals were allowed to mate (one male paired with two females). There was no statistically significant difference in pregnancy rate or fetal number and weight in the female rats mated with the two groups of treated males at 3 weeks' gestation or in serum FSH, Prog, and T, or compared with the control group. Although there were temporary histologic changes in testicular tissue, the rat testes appeared to be functionally resistant to the shock wave energy levels used in this experiment.

[Intracerebroventricular injection of interleukin 1 receptor antagonist antagonises on the generation of immuno-suppressive factor in restraint mice].

Our previous work showed that a lymphocyte proliferation suppressing factor could be found in the serum of restraint mice. In the present work, it was found that intracerebroventricular (icv) injection of IL-1 receptor antagonist (IL-1Ra) was found capable of suppressing the production of such a serum protein under restraint stress. Nearly complete suppression could be achieved by 5.0 micrograms IL-1Ra. Intracerebroventricular injection of IL-1 beta (1 pg), however, increased the generation of the supressive protein. Neither intraperitoneal (ip) injection of IL-1Ra or IL-1 beta had any effect on the generation of the protein. The fact that icv. injection of a very small dose of IL-1 beta (0.06 fmol) was effective on the generation of the supressive protein led us to suggest that IL-1 in brain might act as an important mediator between CNS and the immune system.

The role of actin in changes of cell shape and steroidogenesis in mouse Y-1 cells stimulated by ACTH--immunocytochemical studies.

We investigated the immunocytochemical localization of two kinds of representative cytoskeletal proteins (tubulin and actin) and the morphology of Y-1 mouse adrenal tumor cells under ACTH stimulation at the light and electron microscopic levels. After ACTH stimulation, Y-1 cells showed the rounding-up phenomenon and increased steroidogenesis. Meanwhile, actin was accumulated near the cell membrane and formed filaments. Electron microscopically, stress fibers disappeared with ACTH administration. However, changes in the tubulin localization (main element of the microtubules) were not conspicuous. Cytochalasin B which blocks formation of actin filaments induced rounding-up of Y-1 cells and inhibited increases of steroid synthesis induced by ACTH. Colchicine caused disappearance of the microtubule-organizing center, but the shape of Y-1 cells was not changed. These results suggested that actin-filaments may be the main filament involved in the changes of cell shape and the increased steroidogenesis induced by ACTH.

[Clinical observation on multiple organ dysfunction syndrome due to fish gall bladder poisoning].

OBJECTIVE: To study the functional changes of liver, kidney, myocardium and gastro-intestine after fish gall bladder poisoning and the pathogenic mechanism of acute renal failure. METHODS: The liver and kidney function, myocardial enzyme, urinary N-acetyl-beta-D-glucosaminidase (N-AG), 24 hrs intake and output volume of liquid and kidney B-ultrasonographic examination in 11 patients of severe acute fish gall bladder poisoning were observed. And kidney biopsy was carried out in one patient under B-ultrasonography for understanding the renal pathological changes. RESULTS: All the 11 patients were cured with disappearance of clinical symptoms. After the poisoning the order of the severity of organ damage were kidney, liver, myocardium and gastro-intestine tract. The levels of blood creatinine, blood urea nitrogen, urinary N-AG, glutamic-pyruvic transaminase, total bilirubin were lowered significantly after treatment. Biopsy examination under light microscope showed toxic damage of renal tubules mainly in proximal tubules, and under electron microscope, the pathologic changes were mitochondrial vacuolar degeneration of tubular epithelial cells, swelling of epithelial cells, partial fusion of processes in glomeruli and narrowing of saccular cavity. CONCLUSION: Fish gall bladder poisoning could cause acute multiple organ dysfunction syndrome (MODS), the affected organs in order of severity of damage were kidney, liver, myocardium and gastro-intestine tract. In kidney the damage was mainly at the proximal tubules. Urinary NAG is a sensitive criterion for determining the diagnosis and prognosis of renal tubular dysfunction.