[Clinicopathological characteristics of gastric SMARCA4-deficient undifferentiated/rhabdoid carcinoma].

Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of gastric SMARCA4-deficient undifferentiated carcinoma, and to discuss the daily diagnostics of this entity and analyze its prognosis. Methods: The cases of gastric SMARCA4-deficient undifferentiated carcinoma diagnosed at the Department of Pathology, Peking University Cancer Hospital, China from January 2010 to August 2022 were collected. The histological sections were reviewed, the immunohistochemical results and clinicopathological features were analyzed, and relevant literature was reviewed. Results: Pure foci of undifferentiated carcinoma were seen in 7 cases, and 1 case was accompanied by a moderately differentiated tubular adenocarcinoma component. Undifferentiated carcinoma foci showed similar sheet-like or solid diffuse growth pattern, medium-sized tumor cells characterized by 1-2 nucleoli, and abundant cytoplasm and rhabdoid appearance. The average patient age was 65±8 years. Six patients were male and 2 were female. Immunohistochemical staining showed that undifferentiated carcinoma of all 8 tumors were negative for SMARCA4 (BRG1). Among 7 patients who underwent SMARCA2 (BRM) and SMARCB1 (INI1) staining, 4 cases showed loss of BRM expression, 2 cases showed weakly positive staining, and 1 case was diffusely positive, but all 7 cases were diffusely strong positive for INI1. The neuroendocrine marker, synaptophysin, was weakly positive in 5 cases, while CgA and CD56 were negative in 8 cases. Ki-67 index was more than 70%. Two cases were mismatch repair deficient and showed the loss of MLH1/PMS2 expression, while 1 case showed only MSH2 loss. PD-L1 staining showed that combined positive score (CPS)≥1 in 4 cases (CPS ranging from 1 to 55) and CPS<1 in the other 3 cases. Four patients had clinical stage Ⅳ disease. Two of them died within 3 months after diagnosis. Conclusions: Gastric SMARCA4-deficient undifferentiated carcinoma/rhabdoid carcinoma is a rare group of highly malignant tumors with a poor prognosis. Loss of the core subunit of SWI/SNF complex may be associated with the development of dedifferentiated histological pattern and aggressive tumor progression, which may be more frequently accompanied with mismatch repair deficiency.

BMSCs attenuate hepatic fibrosis in autoimmune hepatitis through regulation of LMO7-AP1-TGFß signaling pathway.

OBJECTIVE: In a previous study, we reported that transplantation of bone mesenchymal stem cells (BMSCs) significantly attenuated liver damage in a mouse autoimmune hepatitis (AIH) model. Moreover, expression of the LIM domain protein, LMO7, correlated positively with the invasive capacity of hepatoma cells. However, whether LMO7 plays a role in inflammation and fibrosis of AIH remains unknown. This investigation aimed to explore the effect of BMSC transplantation on LMO7 and the role of LMO7 in hepatic fibrosis. MATERIALS AND METHODS: S100-induced murine AIH and LPS-induced hepatocyte injury models were successfully established. Three doses of BMSCs were injected into AIH mice via the tail vein. LPS-treated AML12 cells were co-cultured with BMSCs in vitro. Small interfering (si) LMO7 RNA and T5224 (a specific inhibitor of AP-1) were used to demonstrate the relationship between LMO7-AP1-transforming growth factor (TGF)-ß. RESULTS: Pathological examination and serum alanine and aspartate aminotransferase levels indicated that liver damage was notably ameliorated in the BMSC-treated mice. LMO7 level was upregulated, while AP-1 and TGF-ß levels were downregulated upon intervention with BMSCs. AP-1 expression was upregulated in the siLMO7 group, whereas TGF-ß level was downregulated in the T5224 group when compared to those in the control group. CONCLUSIONS: BMSC transplantation significantly limits liver fibrosis and upregulates the expression of LMO7. LMO7 inhibits the TGF-ß pathway by inhibiting AP-1. This implies that BMSCs are a potential means of treating liver fibrosis. This approach has important implications for the treatment of AIH and other fibrotic diseases.

[Ultrasonographic assessment and differentiation of spontaneous degenerating cystic thyroid nodules and papillary thyroid carcinomas].

Objective: To analyze the features of degenerating cystic thyroid nodules (DCTN) on conventional ultrasound and contrast-enhanced ultrasound (CEUS), and to explore the differentiation between DCTN and papillary thyroid carcinomas (PTC). Methods: A total of 46 DCTN (39 cases, including 12 males and 27 females, with an age range of 25 to 76 years) and 36 PTC (32 cases, including 8 males and 24 females, with an age range of 23 to 68 years) diagnosed via fine- needle aspiration (FNA) or surgery from February 2019 to January 2020 in the First Affiliated Hospital of Nanchang University were enrolled. The size, shape, margin, echogenicity, presence of shadowing, calcification and vascularity of DCTN and PTC were retrospectively evaluated, and 28 DCTN and 30 PTC underwent CEUS were separately analyzed and compared.The t test, χ² test or Fisher's exact test were implemented to compare the features of ultrasound among the two groups. The binary Logistic regression test was performed to determine whether the feature whose difference was statistically significant was an independent predictive risk factor. Results: A univariate analysis indicated that DCTN more frequently showed wider-than-tall shapes, marked hypoechogenicity, well-defined margin and no or dot-lined enhancement (wider-than-tall shapes: 36 vs. 17, χ2=8.511; well-defined margin: 30 vs. 15, χ2=4.523; marked hypoechogenicity: 27 vs. 9, χ2=9.310; no or dot-lined enhancement: 24 vs. 3, χ2=33.369; all P＜0.05). A multivariate analysis demonstrated that wider-than-tall shapes, well-defined margin and marked hypoechogenicity were independent predictors for DCTN (OR values were 5.204, 3.134 and 5.042, P values were 0.003, 0.031, and 0.003, respectively). Among 28 DCTN, 15 showed a decrease in mean maximum diameter (24.3±11.4 mm) with a mean time span of (18.6±10.5) months between the presence and absence of suspicious ultrasound features. Conclusions: Compared with PTC, DCTN shows the ultrasound characteristics of wider-than-tall shapes, well-defined margin, marked hypoechogenicity and no or dot-lined enhancement pattern. Ultrasound follow-up can help to identify spontaneous DCTN.

[Expression level and prognostic value of PD-L1 in microsatellite instability-high gastric cancer].

Objective: To study the clinicopathological features and PD-L1 expression of microsatellite instability-high (MSI-H) gastric cancer. Methods: The clinicopathological data of the 2 472 patients who had undergone radical surgical resection and been performed immunohistochemical staining of four major mismatch repair (MMR) proteins (MLH1, PMS2, MSH2 and MSH6) from March 2014 to December 2018 at Peking University Cancer Hospital were collected. One hundred and seventy-one patients showed mismatch repair-deficient (dMMR), and microsatellite instability of these patients were detected with polymerase chain reaction (PCR). Then, taken PCR results as the standard, PD-L1 was assessed using immunohistochemistry (IHC) in the MSI-H gastric cancers. Results: MSI-H (vs. MSI-L) in gastric cancers was associated with female gender, advanced age, gastric-antrum location, intestinal type, lesion diameter exceeding 5 cm, absence of lymph node metastasis and positive PD-L1 expression (P<0.05, respectively). Combined positive score (CPS) was an independent risk factor (P=0.026, HR=8.385, 95%CI=1.293-54.367). Although no relationship between PD-L1 expression pattern and prognosis was observed,"diffuse-pattern" of the PD-L1 expression was related to lymphatic-vascular invasion (P=0.007) and infiltration depth (P=0.04). Among the patients with MSI-H and PD-L1 positive gastric cancer, the patients who experienced recurrence or died all had the pattern of "diffuse" PD-L1 expression. Also, regarding the expression level and staining pattern of PD-L1, the metastasis lesion of lymph node had a high coincidence with primary site (P=0.45). Conclusions: MSI-H gastric cancer shows distinctive clinicopathological characteristics. The CPS can be used as a prognostic indicator in MSI-H gastric cancers, while the "diffuse-pattern" of PD-L1 expression could possibly be used as a prognostic indicator. The patients with advanced gastric cancer could obtain the expression level and staining pattern of PD-L1 using the biopsy material of metastatic lesions.

Reduced occurrence of ventilator-associated pneumonia after cardiac surgery using preoperative 0.2% chlorhexidine oral rinse: results from a single-centre single-blinded randomized trial.

Since mechanical ventilation after cardiac surgery increases the risk of ventilator-associated pneumonia (VAP), we conducted a prospective randomized controlled trial to investigate the effect of preoperative 0.2% chlorhexidine on postoperative VAP. Ninety-four patients scheduled for heart surgery were randomized to a chlorhexidine group (N = 47) or control (saline) group (N = 47). On the day before surgery, patients gargled three times with 0.2% chlorhexidine or saline 30 min after each meal and 5 min after teeth brushing at bedtime. VAP occurred in 8.5% of the chlorhexidine group and in 23.4% of the controls. Preoperative chlorhexidine mouthwash reduced the incidence of postoperative VAP significantly.

Cesarean scar pregnancy associated with uterine artery pseudoaneurysm: a case report.

Cesarean scar pregnancy (CSP) and uterine artery pseudoaneurysms (UAPs) are associated with massive uterine hemorrhage and mortality. As a result of their low prevalence, the occurrence of CSP and a UAP in the same patient is extremely rare. The authors describe a patient who was initially misdiagnosed with trophoblastic disease by ultrasonography. The lesion had a blood-rich area of 75 x 65 x 61 mm on ultrasonography. Pelvic angiography revealed a UAP in the right side of the uterus. The patient underwent uterine artery embolization (UAE) immediately after the correct diagnosis was confirmed. Curettage was undertaken under ultrasound guidance one week postoperatively. Histopathological examination of the resected tissue revealed degenerative chorionic villi and trophoblasts with blood clots. Serum levels of beta-human chorionic gonadotropin (ß-hCG) and uterine ultrasound recovered to normal levels two weeks and three months later, respectively.

Association between perioperative glucose levels and adverse outcomes in infants receiving open-heart surgery with cardiopulmonary bypass for congenital heart disease.

There is no consensus that hyperglycaemia is an independent predictor of morbidity-mortality in children. This retrospective observational study aimed to assess the association between abnormal perioperative glucose levels and adverse outcomes in infants receiving open-heart surgery with cardiopulmonary bypass. The records of a total of 233 infants who underwent cardiopulmonary bypass for a variety of congenital cardiac procedures between January and December 2010 were reviewed. The blood glucose levels, demographic and perioperative information were recorded. Patients who experienced complications (n=91) were compared with those who did not (n=142). We found both intraoperative and postoperative glucose levels increased compared to the preoperative values (P<0.001). Thirty patients (12.8%) experienced hyperglycaemia and 15 patients (6.4%) experienced at least one episode of hypoglycaemia during surgery. Within the first two days after surgery, 12 (5.2%) patients experienced hyperglycaemia and 32 (13.7%) became hypoglycaemic in the paediatric intensive care unit. However, the abnormal perioperative glucose levels were not associated with increased adverse outcomes. After adjusting for other potential variables, lower weight at surgery, longer surgery time and hospital length-of-stay are the independent predictors of morbidity-mortality. Our findings suggest that perioperative hyperglycaemia and mild transient hypoglycaemia do not appear to be detrimental to infants with congenital heart disease, although we did not assess neurological outcomes. Nevertheless, due to the limitations of the retrospective design of this study and its limited power, more thorough clinical randomised controlled trials are needed.

A novel rat model of chronic heart failure following myocardial infarction.

In this report, we describe an improved method for the establishment of reproducible congestive heart failure (CHF) in a rat model. The area of myocardial infarction (MI) after ligation of the left anterior descending (LAD) coronary artery was quantified. Histological changes, heart function detected by echocardiography and isolated Langendorff perfusion, and selected biochemical factors were monitored after ligation of the LAD. Contrary to previous beliefs, thoracotomy in the second intercostal space provided a much better visualization of and easier access to the LAD and significantly reduced the mortality rate. Surface electrocardiogram (ECG) showed that the S-T interval was arched raised upward immediately after ligation. Typical morphological and functional changes of CHF were observed after LAD ligation. Cardiomyocytes in the infarcted zone were depleted and deranged. Biochemical analysis and enzyme-linked immunosorbent assay (ELISA) showed that superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and nitric oxide (NO) levels were significantly lowered in rats with MI than in the normal and sham groups, whereas serum malondialdehyde (MDA), MB isoenzyme of creatine kinase (CK-MB), cardiac troponin (cTnT) and C-reactive protein (CRP) levels were elevated. After MI, N-terminal pro-brain natriuretic peptide (NT-proBNP) was increased but insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF) in culture supernatant were lower than in the normal and sham groups. We present an improved model for maximal reproducibility of experimental CHF in rats which allows the study of molecular and physiological variables in relation to CHF.

Enhanced angiotensin converting enzyme 2 regulates the insulin/Akt signalling pathway by blockade of macrophage migration inhibitory factor expression.

BACKGROUND AND PURPOSE: Macrophage migration inhibitory factor (MIF) is now known to be a pro-inflammatory cytokine associated with insulin resistance. Our aim was to investigate whether angiotensin converting enzyme 2 (ACE2) could modulate the expression of MIF and the insulin/Akt-endothelial nitric oxide (NO) synthase (eNOS) signalling in a human endothelial cell line (EAhy926). EXPERIMENTAL APPROACH: A recombinant plasmid encompassing human ACE2 gene was constructed and transfected into the EAhy926 cells. The mRNA, phosphorylation and protein levels of p22phox, MIF, Akt and eNOS in endothelial cells were determined by real-time PCR and Western blot analysis, respectively. KEY RESULTS: Gene transfer of ACE2 suppressed the expression of p22phox and MIF induced by angiotensin (Ang) II and Ang IV, accompanied by a decreased level of malondialdehyde in cells. In addition, Ang II diminished insulin-stimulated phosphorylation of Akt (at Ser(473)) and eNOS (at Ser(1177)) and NO generation, effects which were reversed by ACE2 gene transfer and anti-MIF treatment in endothelial cells. CONCLUSIONS AND IMPLICATIONS: The results reveal that gene transfer of ACE2 regulated Ang II-mediated impairment of insulin signalling and involved the Akt-eNOS phosphorylation pathway. These beneficial effects of ACE2 overexpression appear to result mainly from blocking MIF expression in endothelial cells, suggesting that the ACE2 gene may be a novel therapeutic target for diseases related to inflammation and insulin resistance.

Fatal bilateral chylothorax in mice lacking the integrin alpha9beta1.

Members of the integrin family of adhesion receptors mediate both cell-cell and cell-matrix interactions and have been shown to play vital roles in embryonic development, wound healing, metastasis, and other biological processes. The integrin alpha9beta1 is a receptor for the extracellular matrix proteins osteopontin and tenacsin C and the cell surface immunoglobulin vascular cell adhesion molecule-1. This receptor is widely expressed in smooth muscle, hepatocytes, and some epithelia. To examine the in vivo function of alpha9beta1, we have generated mice lacking expression of the alpha9 subunit. Mice homozygous for a null mutation in the alpha9 subunit gene appear normal at birth but develop respiratory failure and die between 6 and 12 days of age. The respiratory failure is caused by an accumulation of large volumes of pleural fluid which is rich in triglyceride, cholesterol, and lymphocytes. alpha9(-/-) mice also develop edema and lymphocytic infiltration in the chest wall that appears to originate around lymphatics. alpha9 protein is transiently expressed in the developing thoracic duct at embryonic day 14, but expression is rapidly lost during later stages of development. Our results suggest that the alpha9 integrin is required for the normal development of the lymphatic system, including the thoracic duct, and that alpha9 deficiency could be one cause of congenital chylothorax.

Differential bacterial survival, replication, and apoptosis-inducing ability of Salmonella serovars within human and murine macrophages.

Salmonella serovars are associated with human diseases that range from mild gastroenteritis to host-disseminated enteric fever. Human infections by Salmonella enterica serovar Typhi can lead to typhoid fever, but this serovar does not typically cause disease in mice or other animals. In contrast, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis, which are usually linked to localized gastroenteritis in humans and some animal species, elicit a systemic infection in mice. To better understand these observations, multiple strains of each of several chosen serovars of Salmonella were tested for the ability in the nonopsonized state to enter, survive, and replicate within human macrophage cells (U937 and elutriated primary cells) compared with murine macrophage cells (J774A.1 and primary peritoneal cells); in addition, death of the infected macrophages was monitored. The serovar Typhimurium strains all demonstrated enhanced survival within J774A.1 cells and murine peritoneal macrophages, compared with the significant, almost 100-fold declines in viable counts noted for serovar Typhi strains. Viable counts for serovar Enteritidis either matched the level of serovar Typhi (J774A. 1 macrophages) or were comparable to counts for serovar Typhimurium (murine peritoneal macrophages). Apoptosis was significantly higher in J774A.1 cells infected with serovar Typhimurium strain LT2 compared to serovar Typhi strain Ty2. On the other hand, serovar Typhi survived at a level up to 100-fold higher in elutriated human macrophages and 2- to 3-fold higher in U937 cells compared to the serovar Typhimurium and Enteritidis strains tested. Despite the differential multiplication of serovar Typhi during infection of U937 cells, serovar Typhi caused significantly less apoptosis than infections with serovar Typhimurium. These observations indicate variability in intramacrophage survival and host cytotoxicity among the various serovars and are the first to show differences in the apoptotic response of distinct Salmonella serovars residing in human macrophage cells. These studies suggest that nonopsonized serovar Typhimurium enters, multiplies within, and causes considerable, acute death of macrophages, leading to a highly virulent infection in mice (resulting in death within 14 days). In striking contrast, nonopsonized serovar Typhi survives silently and chronically within human macrophages, causing little cell death, which allows for intrahost dissemination and typhoid fever (low host mortality). The type of disease associated with any particular serovar of Salmonella is linked to the ability of that serovar both to persist within and to elicit damage in a specific host's macrophage cells.

Orthognathic surgery correction of mandibular hypoplasia accompanying obstructive sleep apnea syndrome.

OBJECTIVE: To examine the surgical correction methods for treating cases of severe mandibular hypoplasia accompanying obstructive sleep apnea syndrome (OSAS). METHODS: Sixteen cases of severe mandibular hypoplasia were studied in which OSAS was documented by polysomnography (PSG) and cephalometric study. The obstructive site was at the base of the tongue. Surgical procedures such as temporomandibular joint (TMJ) reconstruction and bimaxillary, chin, and hyoid bone advancement were performed to improve each patient's profile, function, and occlusion, and to treat the OSAS. RESULTS: There were great improvements in patient's sleep and daytime quality of life. The pre- and postoperative changes of most PSG values and some cephalometric values (SNB, PAS) were statistically significant. CONCLUSIONS: Severe mandibular hypoplasia can cause not only abnormalities in profile and occlusion but also OSAS. The evaluation of OSAS and its treatment effects depend on PSG. It is also very important to confirm the obstructive site in the upper airway by cephalometric study and fiberoptic endoscopy. Orthognathic surgery procedures can advance the maxillary, chin, and hyoid bone, and expand the upper airway simultaneously. These procedures can treat OSAS. Cases of TMJ ankylosis with OSAS should be treated step by step.

Physical limitations on Salmonella typhi entry into cultured human intestinal epithelial cells.

Kinetic studies of Salmonella typhi invasion of INT407 cells at different multiplicities of infection (MOIs) have revealed a strict physical limitation on S. typhi entry at MOIs of >/=40. Staining of infected monolayers to distinguish intracellular from extracellular bacteria revealed that all monolayer cells are susceptible to infection and that internalized bacteria are typically contained in one to three separate clusters per cell during the first 60 min. Scanning and transmission electron microscopic analyses of time course-infected monolayers showed that at early times postinfection, bacteria bind to shortened, coalesced microvilli in one to three focal aggregate structures per host cell surface. As reported previously for S. typhimurium, focal aggregates progress to conical membrane ruffles that appear to engulf one or a few centrally contained S. typhi cells by a macropinocytic process, which enhanced the entry of simultaneously added Escherichia coli HB101 about 30-fold. Additionally, kinetic studies showed that at an MOI of approximately 400, maximal S. typhi entry is virtually completed within 30 to 35 min. Monolayers pretreated with S. typhi for 30 min to saturate the entry process were severely reduced in the ability to internalize subsequently added kanamycin-resistant strains of S. typhi or S. typhimurium, but E. coli HB101(pRI203) expressing the cloned Yersinia inv gene was not reduced in entry. In invasion inhibition assays, anti-beta1 integrin antibodies markedly reduced E. coli HB101(pRI203) invasion efficiency but did not reduce S. typhi entry. Collectively, these data provide direct physical and visual evidence which indicates that S. typhi organisms are internalized at a limited number (i.e., two to four) of sites on host cells. S. typhi and S. typhimurium likely share INT407 cell entry receptors which do not appear to be members of the beta1 integrin superfamily.

Mutation in the peb1A locus of Campylobacter jejuni reduces interactions with epithelial cells and intestinal colonization of mice.

Campylobacter jejuni is one of the leading causes of bacterial diarrhea throughout the world. We previously found that PEB1 is a homolog of cluster 3 binding proteins of bacterial ABC transporters and that a C. jejuni adhesin, cell-binding factor 1 (CBF1), if not identical to, contains PEB1. A single protein migrating at approximately 27 to 28 kDa was recognized by anti-CBF1 and anti-PEB1. To determine the role that the operon encoding PEB1 plays in C. jejuni adherence, peb1A, the gene encoding PEB1, was disrupted in strain 81-176 by insertion of a kanamycin resistance gene through homologous recombination. Inactivation of this operon completely abolished expression of CBF1, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. In comparison to the wild-type strain, the mutant strain showed 50- to 100-fold less adherence to and 15-fold less invasion of epithelial cells in culture. Mouse challenge studies showed that the rate and duration of intestinal colonization by the mutant were significantly lower and shorter than with the wild-type strain. In summary, PEB1 is identical to a previously identified cell-binding factor, CBF1, in C. jejuni, and the peb1A locus plays an important role in epithelial cell interactions and in intestinal colonization in a mouse model.

Inactivation of the integrin beta 6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin.

The integrin alpha v beta 6 is only expressed in epithelial cells. In healthy adult epithelia, this receptor is barely detectable, but expression is rapidly induced following epithelial injury. Mice homozygous for a null mutation in the gene encoding the beta 6 subunit had juvenile baldness associated with infiltration of macrophages into the skin, and accumulated activated lymphocytes around conducting airways in the lungs. Beta 6-/- mice also demonstrated airway hyperresponsiveness to acetylcholine, a hallmark feature of asthma. These results suggest that the epithelial integrin alpha v beta 6 participates in the modulation of epithelial inflammation. Genetic or acquired alterations in this integrin could thus contribute to the development of inflammatory diseases of epithelial organs, such as the lungs and skin.

A point mutation in the integrin beta 6 subunit abolishes both alpha v beta 6 binding to fibronectin and receptor localization to focal contacts.

The integrin alpha v beta 6 was initially identified from primary cultures of airway epithelial cells. This integrin is expressed in bronchiolar and alveolar epithelium during development and in settings of injury and/or inflammation and mediates attachment of epithelial cells to fibronectin and tenascin. Like other integrins, this receptor localizes to structures called focal contacts in cells plated on appropriate ligands. In the present study, we produced a mutant beta 6 cDNA (beta 6m) containing a single substitution of Asp140 with Ala and transfected mutant (or wild-type) beta 6 cDNA into the human colon carcinoma cell line SW480. In parallel, we used cDNAs truncated just proximal to the transmembrane domain to generate secreted forms of mutant alpha v beta 6 in Chinese hamster ovary (CHO) cells. The mutant beta 6, like the wild type, formed heterodimers with human alpha v that were expressed on the cell surface of SW480 cells and secreted by CHO cells. Secreted alpha v beta 6 containing this point mutation did not bind to fibronectin-Sepharose. Furthermore, in contrast to wild-type beta 6, the mutant form did not allow SW480 cells to bind to fibronectin in the presence of beta 1-blocking antibody and did not localize to focal contacts. Our results confirm that the Asp140 of beta 6, like the corresponding residues in beta 1 (Asp130) and beta 3 (Asp119), is critical for interactions of alpha v beta 6 with ligand, and also suggest that ligand binding to alpha v beta 6 is necessary for localization of this receptor to focal contacts.

Pathogenesis of extrinsic allergic alveolitis and pulmonary fibrosis induced by streptomyces thermohygroscopicus.

There were 48 strains of thermophilic actinomyces isolated from the specimens of mouldy hay and sputum of the patients suffering from farmer's lung (FL). Streptomyces thermohygroscopicus (STHs), one strain of them, was used for this investigation. The microorganisms were injected into the lungs of rabbits and rats by thyrocrico- or tracheocentesis. The results showed that the pathological changes in the lungs including macrophage alveolitis, granuloma formation and diffuse interstitial were similar to that induced by other thermophilic actinomyces. IgG and C3 deposition in the lesions were also observed by immunofluorescence examination. Specific immunocomplexes in the sera of some animals were detected by ELISA with the STH-antisera. The results suggested that STHs was possibly one of the pathogens responsible for FL in China's countryside.