Cystic Disease Research Articles

Acquired Cystic Kidney Diseases in Bangladeshi Rural Populations: A Cross- Sectional Investigation

Acquired cystic kidney disease (ACKD) is a condition characterized by the formation of numerous cysts in the kidneys. It is frequently associated with chronic kidney disease (CKD) and dialysis. Despite its clinical significance, little is known about its prevalence and characteristics among Bangladesh's rural people. Between January and June of 2023, a cross-sectional survey was done with 120 participants from various rural areas of Mymensingh Division, Bangladesh, to observe the prevalence, risk factors, and clinical characteristics of ACKD. Participants were screened for ACKD using ultrasonography. Demographic information, medical history, and pertinent clinical indicators were gathered. Significant connections between ACKD and possible risk variables were identified by statistical analysis. The median dialysis vintage was 33.3 [range:10.6-62.98] months. Renal cysts were seen in 62.5 % (n=74) of participants, 41.6% (n=50) were bilateral. The median [25th-75th percentile] number of cysts in the right kidney was 4 (range: 2-8) and 3 (range: 2-7.3) in the left kidney. ACKD was detected in 29.17% of the study participants. Individuals with a history of CKD and those on prolonged dialysis vintage had significantly greater prevalence. Male populations over 50 years with prolonged dialysis duration were identified as key risk factors for ACKD. ACKD is a significant health hazard in Bangladesh's rural populations, particularly for elderly persons with CKD and those undergoing dialysis. This study aims to investigate the prevalence, clinical characteristics, and associated risk factors of ACKD among rural populations in Bangladesh. Additional longitudinal studies are required to investigate the long-term impact of ACKD on renal function and overall health outcomes in local communities. CBMJ 2024 July: vol. 13 no. 02 P: 218-222

Advanced cystic fibrosis liver disease: Endovascular, endoscopic, radiologic, and surgical considerations.

Up to 90% of people with CF (pwCF) will have some form of hepatobiliary involvement. This manuscript aims to explore the different endovascular, endoscopic, radiological and surgical procedures available to diagnose and manage the most severe form of CF hepatobiliary involvement (CFHBI) known as advanced cystic fibrosis liver disease (aCFLD),seen in 10% of pwCF. These procedures and interventions include liver biopsy, hepatic venous pressure gradient measurement, gastrostomy tube placement to optimize nutrition, paracentesis, endoscopic variceal control of bleeding and portosystemic shunting before liver transplantation. By utilizing advanced diagnostic or surgical techniques, healthcare professionals of pwCF can more effectively manage patients with CFHBI and aCFLD and potentially improve patient outcomes.

Early detection of hepatobiliary involvement in cystic fibrosis: Biomarkers, radiologic methods, and genetic influences.

Cystic fibrosis-related hepatobiliary involvement (CFHBI) is a term used to describe a spectrum of hepatobiliary involvement ranging from a transient elevation of transaminase levels to advanced cystic fibrosis-associated liver disease (aCFLD). While CFHBI is common among people with cystic fibrosis (PwCF), aCFLD is rare impacting only approximately 5%-10% of the CF population. After respiratory/cardiorespiratory issues and transplant-related complications, aCFLD is now the 4th leading cause of mortality among PwCF. Additionally, aCFLD is an independent predictor of all-cause mortality and is associated with significant morbidity. Despite this recognition, our ability to predict those patients at greatest risk for aCFLD, identify early aCFLD, and monitor the incremental progression of CFHBI is lacking. Here, we review the strengths and weaknesses of the common biomarkers and imaging modalities used in the evaluation and monitoring of CFHBI, as well as the current understanding of genetic modifiers related to aCFLD.

Differential diagnosis of cystic and nodular lung diseases

Cystic and nodular lung diseases encompass abroad spectrum of diseases with different etiologies and clinicoradiological presentations. Their differentiation is crucial for patient management but can be complex due to diseases with features of both categories and overlapping radiological patterns. This study aims to describe the imaging features of cystic and nodular lung diseases in high-resolution computed tomography (CT) in detail-primarily based on their etiology-in order to allow amore accurate differential diagnosis of these diseases. Anarrative review based on current literature on the topic was conducted from aclinicoradiological perspective. This paper systematically categorizes the differential diagnosis of cystic and nodular lung disease and provides insights into their radiological patterns and etiologies. It highlights the role of CT in the diagnosis of these diseases and emphasizes the importance of multidisciplinary panels combining expertise from radiology, pulmonology, rheumatology, and pathology. Reliable differential diagnosis of cystic and nodular lung diseases, particularly based on their radiological features alone, remains difficult due to their overlapping and dynamic nature. Multidisciplinary boards should be the clinical standard for accurate work-up of these diseases, as they combine the medical history, symptoms, radiological findings, and, if necessary, histopathological examinations, thus providing amore robust framework for diagnosis and management.

Cyclin-dependent kinase 4 drives cystic kidney disease in the absence of mTORC1 signaling activity

Progression of cystic kidney disease has been linked to activation of the mTORC1 signaling pathway. Yet the utility of mTORC1 inhibitors to treat patients with polycystic kidney disease remains controversial despite promising preclinical data. To define the cell intrinsic role of mTORC1 for cyst development, the mTORC1 subunit gene Raptor was selectively inactivated in kidney tubular cells lacking cilia due to simultaneous deletion of the kinesin family member gene Kif3A. In contrast to a rapid onset of cyst formation and kidney failure in mice with defective ciliogenesis, both kidney function, cyst formation discerned by magnetic resonance imaging and overall survival were strikingly improved in mice additionally lacking Raptor. However, these mice eventually succumbed to cystic kidney disease despite mTORC1 inactivation. In-depth transcriptome analysis revealed the rapid activation of other growth-promoting signaling pathways, overriding the effects of mTORC1 deletion and identified cyclin-dependent kinase (CDK) 4 as an alternate driver of cyst growth. Additional inhibition of CDK4-dependent signaling by the CDK4/6 inhibitor Palbociclib markedly slowed disease progression in mice and human organoid models of polycystic kidney disease and potentiated the effects of mTORC1 deletion/inhibition. Our findings indicate that cystic kidneys rapidly adopt bypass mechanisms typically observed in drug resistant cancers. Thus, future clinical trials need to consider combinatorial or sequential therapies to improve therapeutic efficacy in patients with cystic kidney disease.

Elexacaftor-tezacaftor-ivacaftor use after solid organ transplant.

In 2019, the United States Food and Drug Administration approved a breakthrough therapeutic for cystic fibrosis, elexacaftor-tezacaftor-ivacaftor (ETI), because of its profound effect on lung function in large phase III clinical trials. ETI acts directly on the dysfunctional protein that causes the systemic manifestations of cystic fibrosis and also leads to improvement in nonpulmonary symptoms of cystic fibrosis. Transplant recipients were excluded from the pivotal clinical trials of ETI but may stand to benefit from correction of the underlying protein defect. Drug interactions between the three drugs in ETI and immunosuppression medications are one of the primary concerns about using ETI after transplant. No rigorous studies exist to assess the safety of ETI in transplant recipients. Multiple recent publications describe the use of ETI after solid organ transplantation, including lung and nonlung transplants, and the real-world evidence for drug interactions between ETI and immunosuppression medications. In nonlung transplant recipients, the pulmonary benefits of ETI have been confirmed, but adverse events occur and may have implications for their transplanted organ (e.g. liver biopsy in the setting of elevated transaminases). Lung transplant recipients may have higher rates of ETI discontinuation than nontransplant recipients given a lack of direct pulmonary benefit and frequency of side effects. Drug interactions have not been difficult to manage, with most studies reporting variable rates of mild to moderate increased tacrolimus levels after initiation of ETI. Limited data exist to support the use of ETI after solid organ transplantation and further research is warranted. Given the unknown risks and benefits, case by case consideration of ETI use is indicated when extra-pulmonary manifestations are present in lung transplant recipients with cystic fibrosis. Given the proven benefit in cystic fibrosis lung disease, benefits likely outweigh the risks of ETI for nonlung solid organ transplant recipients.

Outcomes of lung transplantation in cystic fibrosis.

Lung transplantation (LTX) has transformed care for people with cystic fibrosis (pwCF) suffering from advanced cystic fibrosis lung disease (ACFLD), and it has evolved into an accepted therapy for patients with ACFLD across all ages. We review cystic fibrosis as a major indication for LTX, particularly highlighting outcomes including survival, a changing landscape over time, and factors affecting sequelae following LTX in cystic fibrosis. Although some populations such as those undergoing lung retransplantation exhibit inferior posttransplant outcomes, LTX for pwCF provides an excellent long-term survival that has significantly improved over time, likely due to specialized cystic fibrosis center care and recognition of common comorbidities in pwCF post-LTX. There are gaps in post-LTX outcomes for pwCF, including that identified between Canada and the United States, and that seen in adolescents - both of which are likely multifactorial. In particular, the revolution in cystic fibrosis medical therapy with CFTR modulator therapy has resulted in a dramatic decline in programs performing LTX for cystic fibrosis. How durable this effect will remains to be seen. Overall, LTX remains a well accepted ultimate therapy option in patients with ACFLD if compatible with the individual's goals of care, offering an improved quality of life and maximization of overall survival.

Unilateral Renal Cystic Disease

Background: Unilateral renal cystic disease of kidney is a non familial and non progressive disorder, characterized by replacement of the renal parenchyma by a cluster of multiple cysts with a normal contralateral kidney. Case: A 2-day-old newborn baby came to the Urology Department of the Perinatology Department of Andalas University Hospital. The baby with prenatal ultrasound results showed unilateral hydronephrosis and multicystic kidneys. From the postnatal ultrasound, it was found: The right kidney was normal in shape and size; clear differentiation of the cortex and medulla; the pelvic calyx system was not dilated; No stones were seen; There were multiple cystic lesions with regular borders in the renal cortex, the largest cyst size was 5.5x4 cm. The left kidney was normal in shape and size; clear differentiation of the cortex and medulla; The pelvic calyx system was not dilated; No stones or sludge were seen. The impression of multiple renal cysts. The patient was followed up for renal function and cyst development. Conclusion : This case highlights the importance of early diagnosis and follow-up in infants with unilateral renal cystic lesions. Differentiating URCD from other cystic renal diseases is essential for appropriate management and counseling. Further studies are needed to elucidate the pathogenesis and long-term outcomes of URCD.

Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder.

Mucocele formation in dogs is a unique and enigmatic muco-obstructive disease of the gallbladder caused by the amassment of abnormal mucus that bears striking pathological similarity to cystic fibrosis. We investigated the role of cystic fibrosis transmembrane conductance regulatory protein (CFTR) in the pathogenesis of this disease. The location and frequency of disease-associated variants in the coding region of CFTR were compared using whole genome sequence data from 2,642 dogs representing breeds at low-risk, high-risk, or with confirmed disease. Expression, localization, and ion transport activity of CFTR were quantified in control and mucocele gallbladders by NanoString, Western blotting, immunofluorescence imaging, and studies in Ussing chambers. Our results establish a significant loss of CFTR-dependent anion secretion by mucocele gallbladder mucosa. A significantly lower quantity of CFTR protein was demonstrated relative to E-cadherin in mucocele compared with control gallbladder mucosa. Immunofluorescence identified CFTR along the apical membrane of epithelial cells in control gallbladders but not in mucocele gallbladder epithelium. Decreases in mRNA copy number for CFTR were accompanied by decreases in mRNA for the Cl-/[Formula: see text] exchanger SLC26A3, K+ channels (KCNQ1, KCNN4), and vasoactive intestinal polypeptide receptor (VIPR1), which suggest a driving force for change in secretory function of gallbladder epithelial cells in the pathogenesis of mucocele formation. There were no significant differences in CFTR gene variant frequency, type, or predicted impact comparing low-risk, high-risk, and definitively diagnosed groups of dogs. This study describes a unique, naturally occurring muco-obstructive disease of the canine gallbladder, with uncanny similarity to cystic fibrosis, and driven by the underlying failure of CFTR function.NEW & NOTEWORTHY Cystic fibrosis transmembrane conductance regulatory protein (CFTR) genomic variants and expression of mRNA, protein, and electrogenic anion secretory activity of CFTR were characterized in dog gallbladder. Acquired inhibition of CFTR expression by gallbladder epithelium was identified as underpinning a naturally occurring muco-obstructive disease of the dog gallbladder that bears striking pathological similarity to animal models of cystic fibrosis.

Cystic fibrosis hepatobiliary involvement: an update on imaging in diagnosis and monitoring.

Analysis of the liver using imaging for persons with cystic fibrosis (CF) continues to evolve as new medical therapies are developed improving and extending life. In the 2010s, therapies targeted at modulating protein folding became available to those with CF. Therapeutic options have continued to expand, now providing both correction of protein folding and stabilization for most gene mutations that code for the CF transmembrane receptor protein (CFTR). Today, approximately 80% of persons with CF are eligible for highly effective modulator therapy. With these advancements, the impact of CF on the liver has become more complex, adding metabolism of CFTR modulators to intrinsic CF hepatobiliary involvement (CFHBI) and adding not previously appreciated vascular changes within the liver due to increased longevity in persons with CF. A combination of serum biomarkers and imaging is needed to add clarity to the diagnosis and monitoring of the severity of liver disease. A substantial portion of persons with CF will develop at least CFHBI and a subset will develop advanced cystic fibrosis-associated liver disease (aCFLD); therefore, diagnosis and monitoring need to begin in childhood. In this review, we cover the use of and need for imaging, including elastography, ultrasound, and magnetic resonance imaging (MRI), in diagnosing and monitoring CFHBI and its associated complications.

Increased level of TXNIP and nuclear translocation of TXN is associated with end stage renal disease and development of multiplex renal tumours

BackgroundEnd-stage and acquired cystic renal disease (ESRD/ACRD) kidneys are characterized by inflammatory remodelling and multiplex renal cell carcinomas (RCC). Eosinophilic vacuolated tumour (EVT) occurs exclusively in ACRD. The aim of this study was to identify the involvement of thioredoxin-interacting protein (TXNIP) and thioredoxin (TXN) in ESRD/ACRD pathology.MethodsExpression of TXNIP and TXN was examined in histological slides of 6 ESRD and 6 ACRD kidneys, precursor lesions and associated tumours as well as of RCCs from the general population by immunohistochemistry.ResultsStrong TXNIP expression was seen in epithelial cells, myo-fibroblasts and endothelial cells and weak TXN expression in ESRD/ACRD kidneys and tumours. In ACRD specific EVT and its precursors TXN were translocated into nuclei.ConclusionThe impaired TXNIP/TXN redox homeostasis might be associated with development of multiplex cancer especially of EVT in ESRD/ACRD kidney.

A paradigm shift in diagnosis and treatment innovation for mucinous cystic neoplasms of the liver

This study comprehensively explores the clinical characteristics, diagnostic approaches, and treatment methods for liver mucinous cystic neoplasms (MCN). A retrospective analysis was conducted on seven individuals diagnosed with MCN, admitted to the Fifth Medical Center of the PLA General Hospital between October 2016 and May 2023. Preoperative AFP was negative, while CA19-9 was elevated in two cases. Surgical resection was performed for all patients. The patients showed favorable postoperative recovery. Follow-up revealed an excellent overall survival rate, except for one case of invasive carcinoma resulting in tumor recurrence and metastasis 6 months after surgery. MCN poses a diagnostic challenge due to the absence of distinct clinical and radiological features, leading to potential misdiagnosis and inappropriate treatment. Patients with suspected liver cystic diseases should consider the possibility of MCN. Surgical resection has proven to be a practical approach with satisfactory therapeutic outcomes.

Importance of IFT140 in Patients with Polycystic Kidney Disease Without a Family History

Recently, the monoallelic loss-of-function IFT140 variant was identified as a causative gene for autosomal dominant polycystic kidney disease (ADPKD). In patients with polycystic kidneys who have a positive family history, >90% have pathogenic variants in PKD1 or PKD2, whereas only 1% have IFT140. However, approximately 40% of patients with polycystic kidneys without a family history do not have any pathogenic variants in PKD1 and PKD2. We conducted a comprehensive genetic analysis of 157 adult patients with polycystic kidneys whose parents did not have evident polycystic kidneys. We sequenced up to 92 genes associated with inherited cystic kidney disease, including IFT140. Of the 157 patients, 7 (4.5%) presented with monoallelic loss-of-function variants in the IFT140 gene, 51 (32.5%) with pathogenic variants in the PKD1 or PKD2 gene, and 7 (4.5%) with pathogenic variants in other genes related to inherited kidney cystic disease. The proportion of monoallelic loss-of-function IFT140 variants in this cohort was higher than that in previously reported cohorts with polycystic kidneys who had a positive family history. None of the patients with monoallelic loss-of-function IFT140 variants had polycystic liver disease (PLD). Furthermore, patients with IFT140 pathogenic variants had a significantly smaller kidney volume and a remarkably higher estimated glomerular filtration rate (eGFR) than those with PKD1 pathogenic variants (P= 0.01 and 0.03, respectively). Because the phenotype of polycystic kidneys caused by the IFT140 gene is mild, parental kidney disease may be overlooked. Therefore, patients without a positive family history are more likely to carry pathogenic variants in IFT140.

Clinical Trial Validation of Automated Segmentation and Scoring of Pulmonary Cysts in Thoracic CT Scans.

In cystic lung diseases such as lymphangioleiomyomatosis (LAM), a CT-based cyst score that measures the percentage of the lung volume occupied by cysts is a common index of the cyst burden in the lungs. Although the current semi-automatic measurement of the cyst score is well established, it is susceptible to human operator variabilities. We recently developed a fully automatic method incorporating adaptive features in place of manual adjustments. In this clinical study, the automatic method is validated against the standard method in several aspects. These include the agreement between the cyst scores of the two methods, the agreement of each method with independent tests of pulmonary function, and the temporal consistency of the measurements in the consecutive visits of the same patients. We found that the automatic method agreed with the standard method as well as the agreement between two trained operators running the same standard method; both methods obtained the same level of correlation with laboratory pulmonary function tests; the automated method had better temporal consistency than the standard method (p < 0.0001). The study indicates that the automatic method could replace the standard method and provide better consistency in assessing the extent of cystic changes in the lungs of patients.

Interpretation of inflammatory markers in lung cyst hydatid disease.

Studies on alterations in inflammatory markers and risk factors for perforation in hydatid cysts of the lung are rare. In our study, we planned to investigate the effect of inflammatory markers on prognosis of hydatid cyst disease. 37 patients underwent surgery for pulmonary hydatid cyst between February 2022 and October 2023 and analyzed retrospectively. Inflammatory markers were calculated from preoperative and postoperative 3rd-month peripheral blood results. Cyst size was 58.5 ± 28.0mm, 5 patients had bilateral cysts and 11 patients had multifocal cysts. Preoperative white blood cell, white blood cell difference, preoperative and postoperative eosinophils, preoperative neutrophils, neutrophils difference, preoperative systemic immune inflammatory index, systemic immune inflammatory index difference and preoperative eosinophil lymphocyte ratio were higher in patients with perforated cysts, the cut-off value for preoperative white blood cell for perforation was 10,535, preoperative cut-off value for eosinophils was 230, preoperative cut-off value for neutrophils was 8815, the cut-off value for preoperative systemic immune inflammatory index was 1129.83 and the cut-off value for preoperative eosinophil-lymphocyte ratio was 0.09. In patients with preoperative eosinophil, neutrophil, white blood cell, eosinophil-lymphocyte ratio and systemic immune inflammatory index values above the cut-off value, the probability of perforation increased 7.5, 13.6, 6.3, 9.6, and 9.3 times, respectively.

Interstitial lung diseases : From imaging to treatment

The role of radiology in the diagnosis of interstitial lung diseases (ILDs) has evolved over time, in part replacing histology. Radiology now represents a pillar of diagnostics and monitoring in ILDs. To what extent does radiology influence diagnostics and treatment in ILDs? Aliterature review was conducted, and current findings were discussed in the context of clinical data. Radiology plays acrucial role in the diagnosis of ILDs. Within the framework of the multidisciplinary conference, it provides specific CT patterns such as usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and organizing pneumonia (OP), or helps in identifying cystic lung diseases. Multicompartment diseases can be detected, and pulmonary hypertension or extrapulmonary involvement of the respective diseases can be suspected. Progressive pulmonary fibrosis requires radiologic assessment as one of the required criteria. Interstitial lung abnormalities are usually detected by radiological studies performed for an unrelated indication. Radiology plays an important role within the multidisciplinary conference to determine both diagnosis and treatment with antifibrotic or anti-inflammatory drugs, or a combination of both.

Incorporating genetic testing into a routine kidney clinic.

Incorporating genetic testing in routine outpatient nephrology clinic can improve on chronic kidney disease (CKD) diagnosis and utilization of precision medicine. We sent a genetic test on patients with atypical presentation of common kidney diseases, electrolytes derangements, and cystic kidney diseases. We were able to identify a gene variant contributing to patients' kidney disease in more than half of our cohort. We then showed that patients with ApoL1 risk allele have likely worse kidney disease, and we were able to confirm genetic focal segmental glomerulosclerosis (FSGS) in 2 patients and avoid unnecessary immunosuppression. Genetic testing has also improved our operation to establish a polycystic kidney disease excellence center by confirming our diagnosis, especially in patients without a well-defined family history. In conclusion, utilizing genetic testing in a routine outpatient renal clinic did not cause any burden to either patients or nephrologists, with minimal administrative effort and no financial cost to our patients. We expect that genetic testing in the right setting should become routine in nephrology to achieve a patient-centered precision medicine with less invasive means of kidney disease diagnosis.

Comparative sensitivity of early cystic fibrosis lung disease detection tools in school aged children

BackgroundEffective detection of early lung disease in cystic fibrosis (CF) is critical to understanding early pathogenesis and evaluating early intervention strategies. We aimed to compare ability of several proposed sensitive functional tools to detect early CF lung disease as defined by CT structural disease in school aged children. Methods50 CF subjects (mean±SD 11.2 ± 3.5y, range 5–18y) with early lung disease (FEV1≥70 % predicted: 95.7 ± 11.8 %) performed spirometry, Multiple breath washout (MBW, including trapped gas assessment), oscillometry, cardiopulmonary exercise testing (CPET) and simultaneous spirometer-directed low-dose CT imaging. CT data were analysed using well-evaluated fully quantitative software for bronchiectasis and air trapping (AT). ResultsCT bronchiectasis and AT occurred in 24 % and 58 % of patients, respectively. Of the functional tools, MBW detected the highest rates of abnormality: Scond 82 %, MBWTG RV 78 %, LCI 74 %, MBWTG IC 68 % and Sacin 51 %. CPET VO2peak detected slightly higher rates of abnormality (9 %) than spirometry-based FEV1 (2 %). For oscillometry AX (14 %) performed better than Rrs (2 %) whereas Xrs and R5-19 failed to detect any abnormality. LCI and Scond correlated with bronchiectasis (r = 0.55–0.64, p < 0.001) and AT (r = 0.73–0.74, p < 0.001). MBW-assessed trapped gas was detectable in 92 % of subjects and concordant with CT-assessed AT in 74 %. ConclusionsSignificant structural and functional deficits occur in early CF lung disease, as detected by CT and MBW. For MBW, additional utility, beyond that offered by LCI, was suggested for Scond and MBW-assessed gas trapping. Our study reinforces the complementary nature of these tools and the limited utility of conventional oscillometry and CPET in this setting.

Cystic diseases of the Lungs

Cystic diseases of the Lungs

Ovarian leukocytes: Association with follicular persistence and cyst formation in dairy cows

One of the initial causes of cystic ovarian disease (COD) is a failure in the normal ovulation mechanism. This study aimed to characterize the populations of immune cells (T-lymphocytes, B-lymphocytes, monocytes-macrophages and granulocytes) present in the ovary of cows with COD and induced follicular persistence, and evaluate their relation with follicular persistence and cyst formation. The follicular persistence model was developed using a progesterone (P4) slow-release intravaginal device, to obtain subluteal concentrations of P4. Results evidenced that T-lymphocytes, B-lymphocytes and monocytes-macrophages in the cortex, medulla, and theca externa and interna of dominant follicles were higher in the control group than in the COD and all persistence groups. Granulocytes in the medulla and theca externa of dominant follicles were lower in the control group than in the COD group, and those in the cortex and medulla were lower in the control group than in the persistence groups. The presence of T-lymphocytes, B-lymphocytes and granulocytes in the follicular fluid was abundant, especially that of granulocytes, without differences between control and COD cows. These results suggest that the immune system potentially plays a role in the local mechanisms of COD pathogenesis in dairy cows. In spontaneous COD and in our follicular persistence model, the distribution of the cells studied was different from that in the control group. However, to our knowledge, this is the first report describing the presence of immune cells in bovine follicular fluid samples and the expression of steroid hormone receptors in infiltrating immune cells in the bovine ovary.