Constructing a Large Language Model to Generate Impressions from Findings in Radiology Reports.

Background The specialization and complexity of radiology makes the automatic generation of radiologic impressions (ie, a diagnosis with differential diagnosis and management recommendations) challenging. Purpose To develop a large language model (LLM) that generates impressions based on imaging findings and to evaluate its performance in professional and linguistic dimensions. Materials and Methods Six radiologists recorded imaging examination findings from August 2 to 31, 2023, at Shanghai General Hospital and used the developed LLM before routinely writing report impressions for multiple radiologic modalities (CT, MRI, radiography, mammography) and anatomic sites (cranium and face, neck, chest, upper abdomen, lower abdomen, vessels, bone and joint, spine, breast), making necessary corrections and completing the radiologic impression. A subset was defined to investigate cases where the LLM-generated impressions differed from the final radiologist impressions by excluding identical and highly similar cases. An expert panel scored the LLM-generated impressions on a five-point Likert scale (5 = strongly agree) based on scientific terminology, coherence, specific diagnosis, differential diagnosis, management recommendations, correctness, comprehensiveness, harmlessness, and lack of bias. Results In this retrospective study, an LLM was pretrained using 20 GB of medical and general-purpose text data. The fine-tuning data set comprised 1.5 GB of data, including 800 radiology reports with paired instructions (describing the output task in natural language) and outputs. Test set 2 included data from 3988 patients (median age, 56 years [IQR, 40-68 years]; 2159 male). The median recall, precision, and F1 score of LLM-generated impressions were 0.775 (IQR, 0.56-1), 0.84 (IQR, 0.611-1), and 0.772 (IQR, 0.578-0.957), respectively, using the final impressions as the reference standard. In a subset of 1014 patients (median age, 57 years [IQR, 42-69 years]; 528 male), the overall median expert panel score for LLM-generated impressions was 5 (IQR, 5-5), ranging from 4 (IQR, 3-5) to 5 (IQR, 5-5). Conclusion The developed LLM generated radiologic impressions that were professionally and linguistically appropriate for a full spectrum of radiology examinations. © RSNA, 2024 Supplemental material is available for this article.

Incidence, predictors, and outcomes of malignant cerebral edema in acute basilar artery occlusion after endovascular treatment: a secondary analysis of the ATTENTION trial.

OBJECTIVE: Malignant cerebral edema (MCE) is a life-threatening complication of ischemic stroke. Few studies have evaluated MCE in patients with acute basilar artery occlusion (BAO) receiving endovascular treatment (EVT). Therefore, the authors investigated the incidence, predictors, and functional outcomes of MCE in BAO patients undergoing EVT. METHODS: This was a post hoc analysis of the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) trial, a prospective, randomized, multicenter clinical trial that compared endovascular treatment with conventional care of patients with BAO at 36 centers in China. Brain edema was retrospectively assessed using the Jauss score for all available follow-up scans, and patients with a Jauss score ≥ 4 were classified as having MCE. Clinical functional independence was defined as a modified Rankin Scale (mRS) score of 0-2, and a good outcome was defined as an mRS score of 0-3 at the 90-day follow-up. Univariate and multivariate analyses were used to explore the predictors of MCE and the impact of MCE on prognosis. RESULTS: A total of 189 patients were analyzed, and 13.2% of patients developed MCE. Multivariate analysis showed that the baseline Glasgow Coma Scale (GCS) score (OR 0.722, 95% CI 0.548-0.950; p = 0.020) and the number of procedures (OR 1.594, 95% CI 1.051-2.419; p = 0.028) were significantly associated with MCE. After adjusting for confounding factors, the presence of MCE was significantly associated with a lower rate of functional independence (OR 0.115, 95% CI 0.023-0.563; p = 0.008), a lower rate of good outcome (OR 0.092, 95% CI 0.023-0.360; p = 0.001), and a higher rate of mortality (OR 5.373, 95% CI 2.055-14.052; p = 0.001) at the 90-day follow-up. CONCLUSIONS: MCE is not uncommon in BAO patients undergoing EVT and is associated with poor outcomes. Baseline GCS score and the number of procedures were predictors of MCE. In clinical practice, it is crucial that physicians identifying MCE after EVT in patients with BAO and identification of MCE will help in the selection of an appropriate pharmacological treatment strategy and close monitoring.

Natural course of perianal abscess in infants: a real-world study.

Natural course of perianal abscess (PA) in infancy remains obscure. This study aimed to investigate the natural course of infants with PA after conservative treatment. A retrospective cohort study was conducted in infants with PA who were treated conservatively (due to the parents' refusal of surgery), for more than 2 months between 2014 and 2020 at a single tertiary center. 153 patients (149 boys and 4 girls) were identified. The median follow-up was 5.3 years (range 3-8.2 years). Initially, 119 patients (77.8%) were completely cured by conservative treatment, and 34 (22.2%) failed. Among the 34 patients, 23 continued conservative treatment (20 cure, 3 fistula formation) and 11 underwent surgery. After conservative treatment, the rate of fistula formation, abscess recurrence, and new-onset abscess were 15.0%, 4.6%, and 6.5%, respectively. Overall, 139 patients (90.8%) were cured conservatively without surgery, and 11 (7.2%) underwent surgical management. In addition, 3 (2.0%) patients developed fistula-in-ano (under observation). PA in infants may be a time-limited and self-limited condition. Conservative management should be the first choice of treatment in most cases. Longer periods of conservative treatment may achieve better clinical outcomes in selected cases. There will be a percentage of patients (about 10%) that would require surgical treatment.

Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway.

Currently, the effect and molecular mechanism of calycosin, the main active ingredient of Qinshi Simiao San, which can alleviate chronic prostatitis (CP), on CP remain unclear. This study aimed to elucidate the potential mechanism of action of calycosin in CP in a rat CP model. The prostate tissue morphology was evaluated based on hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was conducted to evaluate inflammatory cytokine and immune factor levels (secretory immunoglobulin A [SIgA]; immunoglobulin G [IgG]) in prostate tissues and serum. Additionally, representative biomarkers of oxidative stress, including malondialdehyde, superoxide dismutase, and catalase were detected using detection kits, and reactive oxygen species release was evaluated using immunofluorescence staining. Furthermore, the p38 mitogen-activated protein kinase (p38MAPK)/NF-kappaB (NF-κB) signaling pathway was analyzed by western blotting. The results showed that calycosin substantially ameliorated the pathological damage to prostate tissues of the CP rats. Moreover, calycosin significantly downregulated interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha, IgG, and SIgA levels. Furthermore, we found that calycosin considerably suppressed oxidative stress and inhibited the activation of the p38MAPK/NF-κB signaling pathway in rats with CP. In summary, our findings revealed that calycosin protects against CP in rats by inhibiting the p38MAPK/NF-κB pathway.

Tourniquet use benefits to reduce intraoperative blood loss in patients receiving total knee arthroplasty for osteoarthritis: An updated meta-analysis with trial sequential analysis.

PURPOSE: The efficacy and safety of tourniquets use during total knee arthroplasty (TKA) in patients with osteoarthritis remain debated. This updated systematic review and meta-analysis aimed to further evaluate the role of tourniquets use in patients undergoing TKA for knee osteoarthritis by introducing trial sequential analysis. METHODS: PubMed, Embase, and the Cochrane Library were searched. We used the Cochrane risk of bias tool for quality assessment. Statistical heterogeneity across studies was evaluated using Cochran's Q and I2 statistic. Meta-analysis was performed using Stata/SE 14.0, and trail sequential analysis was performed using TSA software version 0.9.5.10 Beta. In addition, qualitative summary was also used to describe results. RESULTS: 15 randomized controlled trials (RCTs) involving 1202 patients were included in the meta-analysis. The pooled results showed that tourniquet use during TKA significantly reduced intraoperative blood loss (mean difference (MD)= -123.84, 95% confidence interval (CI): -163.37 to -84.32, p < .001)and shortened operation time (MD = -4.71, 95% CI: -7.6 to -1.82, p = .001), but there were no significant differences in postoperative blood loss, calculated blood loss, total blood loss, transfusion rate (p = .939), and deep venous thrombosis (DVT) rate between the tourniquet and no-tourniquet groups. TSA confirmed that the result of operation time was false positive, but the results of other outcomes were conclusive. The results of qualitative summary showed conflicting findings in terms of pain, range of motion (RoM) and swelling ratio between the two groups. CONCLUSIONS: Tourniquet use in patients receiving TKA for osteoarthritis benefits to reduce intraoperative blood loss but has no effect on postoperative blood loss, calculated blood loss, total blood loss, operation time, transfusion rate, and DVT rate. In addition, it remains unclear the difference between the tourniquet and non-tourniquet groups in terms of pain, RoM and swelling ratio.

Full-Stokes polarization laser-induced breakdown spectroscopy detection of infiltrative glioma boundary tissue.

The glioma boundary is difficult to identify during surgery due to the infiltrative characteristics of tumor cells. In order to ensure a full resection rate and increase the postoperative survival of patients, it is often necessary to make an expansion range resection, which may have harmful effects on the quality of the patient's survival. A full-Stokes laser-induced breakdown spectroscopy (FSLIBS) theory with a corresponding system is proposed to combine the elemental composition information and polarization information for glioma boundary detection. To verify the elemental content of brain tissues and provide an analytical basis, inductively coupled plasma mass spectrometry (ICP-MS) and LIBS are also applied to analyze the healthy, boundary, and glioma tissues. Totally, 42 fresh tissue samples are analyzed, and the Ca, Na, K elemental lines and CN, C2 molecular fragmental bands are proved to take an important role in the different tissue identification. The FSLIBS provides complete polarization information and elemental information than conventional LIBS elemental analysis. The Stokes parameter spectra can significantly reduce the under-fitting phenomenon of artificial intelligence identification models. Meanwhile, the FSLIBS spectral features within glioma samples are relatively more stable than boundary and healthy tissues. Other tissues may be affected obviously by individual differences in lesion positions and patients. In the future, the FSLIBS may be used for the precise identification of glioma boundaries based on polarization and elemental characterizing ability.

The ACORNS grading scale: a novel tool for the prediction of malignant brain edema after endovascular thrombectomy.

BACKGROUND: To develop and validate a novel tool for predicting the development of malignant brain edema (MBE) in large vessel occlusion stroke patients after endovascular thrombectomy (EVT). METHODS: We used a prospectively registered population of EVT patients from three comprehensive stroke centers. The population was randomly divided into two subsets (7:3): a training cohort and an internal validation cohort. External validation was performed using the Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke Registry in China (ACTUAL) database. MBE was defined as (1) hypodense parenchyma in at least 50% of the middle cerebral artery and signs of local brain swelling, and (2) a midline shift of ≥5 mm at the septum pellucidum or pineal gland with obliteration of the basal cisterns. The model was constructed using logistic regression analysis. The performance of the model was examined in terms of discrimination and calibration. RESULTS: After adjusting for other confounders, baseline National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early CT (ASPECT) scores, a clinical history of hypertension, collateral status, intravenous thrombolysis before thrombectomy, fasting blood glucose, reperfusion status, and occlusion site were found to be independent predictors of MBE. These variables were combined to create the ACORNS grading scale. The areas under the curve in receiver operating curve analysis were 0.850 (95% CI 0.816 to 0.884), 0.874 (95% CI 0.821 to 0.926), and 0.785 (95% CI 0.740 to 0.829) for the training, internal validation, and external validation cohorts, respectively, indicating good discriminative performance in the validation cohorts. CONCLUSIONS: The ACORNS grading scale is an accurate and easily applicable model for the prediction of the development of MBE after EVT.

Endovascular treatment in patients with middle cerebral artery occlusion of different aetiologies.

PURPOSE: The purpose of this study was to evaluate differences in endovascular treatment (EVT) outcomes in M1 segment middle cerebral artery occlusion (MCAO) patients with different pathologic subtypes. METHODS: Patients with MCAO who received EVT from July 2014 to December 2020 were categorized into three groups: embolism without internal carotid artery steno-occlusion (MCAO-E), in situ atherosclerotic thrombosis (MCAO-AS) and embolism from tandem ICA steno-occlusion (MCAO-T). Baseline characteristics, EVT-related factors and clinical outcomes were compared between groups. Multivariable regression analyses were performed to evaluate the relationship between aetiologic classification and outcomes at 90 days after stroke. RESULTS: Among eligible patients (n = 220), MCAO-E (n = 129, 58.6%) was the most common aetiology, followed by MCAO-AS (n = 47, 21.4%) and MCAO-T (n = 44, 20.0%). Patients with MCAO-E were significantly older but had a lower rate of dyslipidaemia and smoking history than those with MCAO-AS. Although patients with MCAO-AS and MCAO-T more often required rescue balloon angioplasty and stenting (p < 0.001), no significant difference in the rate of final recanalization was found. Patients in the MCAO-AS group obtained better functional outcomes (90-day modified Rankin Scale score, 0-2) (p = 0.002) and lower mortality than in the MCAO-E group (p = 0.009). On multivariable logistic regression, we failed to find that stroke subtype was an independent predictor of functional outcomes and mortality. CONCLUSIONS: Patients with acute MCA M1 occlusion stroke due to different pathogeneses had comparable successful recanalization rates and functional independence at 90 days. The optimal management for MCAO patients with different aetiologies requires further research.

Prognosis of Ischemic Stroke Patients Undergoing Endovascular Thrombectomy is Influenced by Systemic Inflammatory Index Through Malignant Brain Edema.

Purpose: The systemic immune inflammatory index (SII), as a new marker, is widely used to predict the disease prognosis. We investigated the predictive value of SII for malignant cerebral edema (MCE) and whether postoperative MCE mediates the relationship between SII and functional prognosis in patients undergoing endovascular thrombectomy (EVT). Patients and Methods: A total of 829 patients with anterior circulation large-vessel occlusive stroke (LVOS) were registered, and 675 (81.4%) met the inclusion criteria. We collected baseline data upon admission, including SII. Postoperative computed tomography was performed to assess the presence and grading of cerebral edema (CED), and MCE was defined as a CED score of 3. A good prognosis was defined as a modified Rankin Scale (mRS) score of 0-2 at the 90-day follow-up. Results: A total of 132 patients developed MCE after EVT. The patients were divided into MCE and non-MCE groups, and univariate and multifactorial analyses were performed. Among these risk factors, an elevated SII was independently correlated with the occurrence of MCE. In addition, the receiver operating characteristic (ROC) curve was used to assess the predictive capability of SII levels for prognosis. The area under the ROC was 0.69, and the optimal critical value was 2.14. In addition, postoperative MCE may partially account for the poorer functional prognosis of patients with elevated SII (regression coefficient changed by 40.3%). Conclusion: The SII is an independent predictor of malignant brain edema after EVT. Postoperative MCE is partly the reason for the poorer prognosis in patients with elevated SII.

[Detection of clinically significant prostate cancer in lesions of PI-RADS score 3 in different histological zones of the prostate and MRI/TRUS fusion prostate biopsy].

Objective: To investigate the detection rate of clinically significant PCa (CSPCa) in lesions of prostate imaging-reporting and data system (version 2) (PI-RADS v2) score 3 in different histological zones of the prostate, the value range of clinical parameters, and the possibility of improving the detection rate by MRI/TRUS fusion prostate biopsy. METHODS: This retrospective study included 297 patients with prostatic lesions of PI-RADS v2 score 3 undergoing transperineal prostate biopsy in Nanjing Drum Tower Hospital from January to December 2019. We analyzed their clinical data, the detection rate of CSPCa in the four histological zones of the prostate and the value range of the clinical parameters. RESULTS: The detection rates of CSPCa in the peripheral zone, transitional zone, central zone and anterior fibromuscular stroma were 23.8%, 11.2%, 40.0% and 50.0%, respectively. In comparison with conventional biopsy, additional MRI/TRUS image fusion biopsy improved the detection rate of CSPCa in the four zones, though with no statistically significant difference. The patients with CSPCa, compared with those in the non-CSPCa group, showed a lower value of free PSA/total PSA (fPSA/tPSA) (0.12 ± 0.05 vs 0.18 ± 0.07) but a higher tPSA level (ï¼»13.06 ± 10.07ï¼½ vs ï¼»8.61 ± 5.86ï¼½ µg/L) and PSA density (PSAD) (ï¼»0.35 ± 0.34ï¼½ vs ï¼»0.16 ± 0.11ï¼½ µg/L2). CONCLUSIONS: In prostate lesions of PI-RADS v2 score 3, the detection rate of CSPCa was higher in the peripheral zone, even higher in the central zone and anterior fibromuscular stroma, than in the transitional zone. Prostatic biopsy is strongly recommended for patients with fPSA/tPSA < 0.12 or PSAD > 0.35 µg/L2, and additional MRI/TRUS image fusion biopsy is preferable for the lesions in the transitional or central zone.

Blood Pressure After Endovascular Thrombectomy and Malignant Cerebral Edema in Large Vessel Occlusion Stroke.

Background: Elevated blood pressure (BP) can cause blood-brain barrier disruption and facilitates brain edema formation. We aimed to investigate the association of BP level after thrombectomy with the development of malignant cerebral edema (MCE) in patients treated with endovascular thrombectomy (EVT). Methods: Consecutive patients who underwent EVT for an anterior circulation ischemic stroke were enrolled from three comprehensive stroke centers. BP was measured hourly during the first 24 h after thrombectomy. MCE was defined as swelling causing a midline shift on the follow-up imaging within 5 days after EVT. Associations of various BP parameters, including mean BP, maximum BP (BPmax), and BP variability (BPV), with the development of MCE were analyzed. Results: Of the 498 patients (mean age 66.9 ± 11.7 years, male 58.2%), 97 (19.5%) patients developed MCE. Elevated mean systolic BP (SBP) (OR, 1.035; 95% CI, 1.006-1.065; P = 0.017) was associated with a higher likelihood of MCE. The best SBPmax threshold that predicted the development of MCE was 165 mmHg. Additionally, increases in BPV, as evaluated by SBP standard deviation (OR, 1.061; 95% CI, 1.003-1.123; P = 0.039), were associated with higher likelihood of MCE. Interpretation: Elevated mean SBP and BPV were associated with a higher likelihood of MCE. Having a SBPmax > 165 mm Hg was the best threshold to discriminate the development of MCE. These results suggest that continuous BP monitoring after EVT could be used as a non-invasive predictor for clinical deterioration due to MCE. Randomized clinical studies are warranted to address BP goal after thrombectomy.

Predictive data clustering of laser-induced breakdown spectroscopy for brain tumor analysis.

Limited by the lack of training spectral data in different kinds of tissues, the diagnostic accuracy of laser-induced breakdown spectroscopy (LIBS) is hard to reach the desired level with normal supervised learning identification methods. In this paper, we proposed to apply the predictive data clustering methods with supervised learning methods together to identify tissue information accurately. The meanshift clustering method is introduced to compare with three other clustering methods which have been used in LIBS field. We proposed the cluster precision (CP) score as a new criterion to work with Calinski-Harabasz (CH) score together for the evaluation of the clustering effect. The influences of principal component analysis (PCA) on all four kinds of clustering methods are also analyzed. PCA-meanshift shows the best clustering effect based on the comprehensive evaluation combined CH and CP scores. Based on the spatial location and feature similarity information provided by the predictive clustering, the PCA-Meanshift can improve diagnosis accuracy from less than 95% to 100% for all classifiers including support vector machine (SVM), k nearest neighbor (k-NN), soft independent modeling of class analogy (Simca) and random forests (RF) models.

Predictors of malignant brain edema after mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: Malignant brain edema (MBE) is a devastating complication in ischemic stroke. Data on MBE in patients who have had mechanical thrombectomy (MT) are relatively scarce. OBJECTIVE: To investigate the incidence, predictors, and clinical outcomes of MBE in patients after MT. METHODS: We included 130 consecutive patients after MT caused by anterior circulation large vessel occlusion stroke, treated with MT. MBE was defined as a midline shift of ≥5 mm on the follow-up imaging within 72 hours after MT. Characteristics of patients at admission and details of treatment were collected. The 90-day modified Rankin scale score was used as a measure of functional outcomes. RESULTS: Of the 130 patients (age, 68.6±10.9 years; male, 50%), 35 (26.9%) patients developed MBE. The patients with MBE had a lower rate of functional independence (OR=7.831; 95% CI 1.731 to 35.427; p=0.008) and significantly higher mortality at 90 days (OR=7.958; 95% CI 2.274 to 27.848; p=0.001) than patients without MBE. In 104 (80%) patients with successful recanalization (modified Thrombolysis in Cerebral Infarction score of 2b-3), 24 (23.1%) patients exhibited MBE. After adjustment for confounding, ICA occlusion (OR=3.746; 95% CI 1.169 to 12.006; p=0.026) and worse collateral score (grade 1 vs grade 0: OR=0.727; 95% CI 0.192 to 2.753; p=0.638; grade 2 vs grade 0: OR=0.130; 95% CI 0.021 to 0.819; p=0.030) were significantly associated with the development of MBE, despite successful recanalization. CONCLUSIONS: MBE after MT is not uncommon and was related to poor functional outcomes. Localization of a vessel occlusion and collateral status may play a role in the development of MBE.

Relationship between Vascular Resistance and Sympathetic Nerve Fiber Density in Arterial Vessels in Children With Sleep Disordered Breathing.

BACKGROUND: Sleep disordered breathing in children is associated with increased blood flow velocity and sympathetic overactivity. Sympathetic overactivity results in peripheral vasoconstriction and reduced systemic vascular compliance, which increases blood flow velocity during systole. Augmented blood flow velocity is recognized to promote vascular remodeling. Importantly, increased vascular sympathetic nerve fiber density and innervation in early life plays a key role in the development of early-onset hypertension in animal models. Examination of sympathetic nerve fiber density of the tonsillar arteries in children undergoing adenotonsillectomy for Sleep disordered breathing will address this question in humans. METHODS AND RESULTS: Thirteen children scheduled for adenotonsillectomy to treat sleep disordered breathing underwent pupillometry, polysomnography, flow-mediated dilation, resting brachial artery blood flow velocity (velocity time integral), and platelet aggregation. The dorsal lingual artery (tonsil) was stained and immunofluorescence techniques used to determine sympathetic nerve fiber density. Sympathetic nerve fiber density was correlated with increased resting velocity time integral (r=0.63; P<0.05) and a lower Neuronal Pupillary Index (r=-0.71, P<0.01), as well as a slower mean pupillary constriction velocity (mean, r=-0.64; P<0.05). A faster resting velocity time integral was associated with a slower peak pupillary constriction velocity (r=-0.77; P<0.01) and higher platelet aggregation to collagen antigen (r=0.64; P<0.05). Slower mean and peak pupillary constriction velocity were associated with higher platelet aggregation scores (P<0.05; P<0.01, respectively). CONCLUSIONS: These results indicate that sympathetic activity is associated with change in both the function and structure of systemic vasculature in children with sleep disordered breathing.

Myo1e impairment results in actin reorganization, podocyte dysfunction, and proteinuria in zebrafish and cultured podocytes.

BACKGROUND: Podocytes serve as an important constituent of the glomerular filtration barrier. Recently, we and others identified Myo1e as a key molecular component of the podocyte cytoskeleton. RESULTS: Myo1e mRNA and protein was expressed in human and mouse kidney sections as determined by Northern blot and reverse transcriptase PCR, and its expression was more evident in podocytes by immunofluorescence. By specific knock-down of MYO1E in zebrafish, the injected larvae exhibited pericardial edema and pronephric cysts, consistent with the appearance of protein in condensed incubation supernate. Furthermore, specific inhibition of Myo1e expression in a conditionally immortalized podocyte cell line induced morphological changes, actin cytoskeleton rearrangement, and dysfunction in cell proliferation, migration, endocytosis, and adhesion with the glomerular basement membrane. CONCLUSIONS: Our results revealed that Myo1e is a key component contributing to the functional integrity of podocytes. Its impairment may cause actin cytoskeleton re-organization, alteration of cell shape, and membrane transport, and podocyte drop-out from the glomerular basement membrane, which might eventually lead to an impaired glomerular filtration barrier and proteinuria.

Expression of novel podocyte-associated proteins sult1b1 and ankrd25.

BACKGROUND/AIMS: Podocytes have a unique function in the renal ultrafiltration that is achieved by expressing proteins that are highly specific to podocytes. In this study, we identified two novel podocyte-associated proteins. METHODS: The expression of sult1b1 and ankrd25 in mouse tissues was studied by RT-PCR. The protein expression was studied by generating polyclonal antibodies that were used in Western blotting and immunohistochemistry. RESULTS: By RT-PCR we detected sult1b1 expression only in glomerular, liver and brain tissues. By immunohistochemistry, sult1b1 was detected in the kidney exclusively in the Golgi apparatus of the podocyte. No expression outside the glomerulus was observed in the kidney. The ankrd25 transcript was detected in most mouse tissues analyzed by RT-PCR. In the kidney, however, immunohistochemistry showed that this protein was expressed only by podocyte, mesangial, and smooth muscle cells. In podocytes, ankrd25 was localized to foot processes. CONCLUSIONS: Identification of these two novel glomerulus-associated proteins opens up possibilities to investigate their role in the renal filter physiology and diseases. We speculate that sult1b1 may be involved in the sulfonylation of podocyte protein podocalyxin, whereas ankrd25 may contribute to controlling actin dynamics in podocyte foot processes.

Poly[[(µ-benzene-1,4-dicarboxyl-ato)bis-[µ-4-(1H-1,3,7,8-tetra-aza-cyclo-penta-[l]phenanthren-2-yl)benzoato]dizinc] tetra-hydrate].

In the title complex, [Zn(2)(C(8)H(4)O(4))(C(20)H(11)N(4)O(2))(2)]·4H(2)O, the Zn(II) atom is six-coordinated by two carboxyl-ate O atoms from one bidentate benzene-1,4-dicarboxyl-ate (1,4-BDC) ligand, two carboxyl-ate O atoms from two different monodentate 4-(1H-1,3,7,8-tetra-aza-cyclo-penta-[l]phenanthren-2-yl)benzoate (HNCP) ligands and two HNCP N atoms. The Zn(II) atoms are bridged by the centrosymmetric 1,4-BDC ligands, forming an extended single-chain structure. Neighbouring single chains are connected by the HNCP ligands from two opposite directions, resulting in a sheet. In addition, there are N-H⋯O hydrogen-bonding inter-actions between adjacent layers. As a result, the polymeric sheets are further extended into a three-dimensional supra-molecular structure.

Flavopiridol reduces malignant transformation of the esophageal mucosa in p27 knockout mice.

The cyclin-dependent kinase (cdk) inhibitor p27 preferentially inactivates cdk complexes required for progression through the G1/S transition. Loss of p27 is associated with aggressive behavior in a variety of tumors, including Barrett's associated adenocarcinoma (BAA). We have previously shown that gastroduodenal-esophageal reflux (GDER) together with N-methyl-N-benzylnitrosamine (MBN) induces Barrett's esophagus (BE) and malignant transformation of the esophageal mucosa in mice. This process is enhanced in a p27 null background. Here, we show that chronic flavopiridol administration sharply reduced the prevalence of BE in GDER/MBN-treated p27 knockout mice when compared to animals treated with diluent only (7 vs 26%, P=0.0079). Similarly, flavopiridol reduced the prevalence of BAA (11 vs 32%, P=0.0098) and overall cancer prevalence (15 vs 60%, P<0.0001). In addition, appropriate molecular targeting by flavopiridol in tumor cells was confirmed by downregulation of cyclin D1, a known target of this pan-cdk inhibitor. The results of this study represent the experimental basis for chemoprevention with cdk inhibitors in human BE and BAA.