[Statistical parametric mapping analysis of 18F-FDG PET in Parkinson's disease with mild cognitive impairment].

Objective: To investigate the characteristics of cerebral metabolism associated with mild cognitive impairment (MCI) Parkinson's disease (PD), cognitive normal PD and normal control to find a PET biomarker for the diagnose and estimate of PD-MCI. Methods: Forty-seven patients diagnosed with PD (included 15 with mild cognitive impairment) and 20 control subjects were enrolled. All the subjects were evaluated with FDG-PET and clinical scale. The statistical parametric mapping (SPM) were analyzed to determine metabolic patterns that may be useful in differentiating between the three groups. Results: SPM analysis showed that significant hypometabolism were observed in both side of front lobe, parietal lobe, left temporal lobe and left occipital lobe; in the contrast, the relative hypermetabolism had been observed in the cerebellum, vermis, hippocampus and supplement motor area (SMA) in patients with PD-MCI. PD without MCI showed hypometabolism in both side of front lob, caudate and putamen. PD-MCI showed that the significant hypermetabolism were in the insular and cerebellum while hypometabolism were in the both side of occipital compared to PD without MCI. Conclusion: A voxel-by-voxel based SPM method i. e. SPM8 analysis by PET scan is an effective way to analysis the FDG uptake pattern of PD patients. The hypermetabolism in the insula and cerebellum and hypometabolism in the both side of occipital may be a biomarker for make a diagnosis of PD-MCI.

DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and Rhesus macaques.

There are well over a quarter of a billion chronic hepatitis B virus (HBV) carriers across the globe. Most carriers are at high risk for development of liver cirrhosis and subsequent progression to hepatocellular carcinoma. It is therefore imperative to develop new approaches for immunotherapy against this infection. Antibodies and cytotoxic T cells to different HBV antigens are believed to be important for reducing viral load and clearing HBV-infected cells from the liver. Some of the major challenges facing current vaccine candidates have been their inability to induce both humoral and cellular immunity to multiple antigenic targets and the induction of potent immune responses against the major genotypes of HBV. In this study, highly optimized synthetic DNA plasmids against the HBV consensus core (HBc) and surface (HBs) antigens genotypes A and C were developed and evaluated for their immune potential. These plasmids, which encode the most prevalent genotypes of the virus, were observed to individually induce binding antibodies to HBs antigens and drove robust cell-mediated immunity in animal models. Similar responses to both HBc and HBs antigens were observed when mice and non-human primates were inoculated with the HBc-HBs cocktails. In addition to the cytotoxic T lymphocyte activities exhibited by the immunized mice, the vaccine-induced responses were broadly distributed across multiple antigenic epitopes. These elements are believed to be important to develop an effective therapeutic vaccine. These data support further evaluation of multivalent synthetic plasmids as therapeutic HBV vaccines.

Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver.

The prevalence of hepatitis B virus (HBV) infection in Asia and sub-Sahara Africa is alarming. With quarter of a billion people chronically infected worldwide and at risk of developing liver cancer, the need for a prophylactic or therapeutic vaccination approach that can effectively induce protective responses against the different genotypes of HBV is more important than ever. Such a strategy will require both the induction of a strong antigen-specific immune response and the subsequent deployment of immune response towards the liver. Here, we assessed the ability of a synthetic DNA vaccine encoding a recombinant consensus plasmid from genotype A through E of the HBV core antigen (HBcAg), to drive immunity in the liver. Intramuscular vaccination induced both strong antigen-specific T cell and high titer antibody responses systematically and in the liver. Furthermore, immunized mice showed strong cytotoxic responses that eliminate adoptively transferred HBV-coated target cells. Importantly, vaccine-induced immune responses provided protection from HBcAg plasmid-based liver transfection in a hydrodynamic liver transfection model. These data provide important insight into the generation of peripheral immune responses that are recruited to the liver-an approach that can be beneficial in the search for vaccines or immune-therapies to liver disease.

The spectrum of T-cell and natural killer/T-cell neoplasms with leukaemic presentation in a single institution in Taiwan.

T cell and natural killer (NK)/T-cell neoplasms are rare and may occasionally present as leukaemia. We retrospectively searched T cell and NK/T-cell tumours in a single institution in Taiwan from January 2000 to December 2009 and identified 137 (19.1%) patients with T cell and NK/T-cell tumours among 718 patients with lymphoid neoplasms. Among these 137 patients, 18 (13.1%) presented with leukaemia including T-lymphoblastic lymphoma/leukaemia (T-LBL), T-cell prolymphocytic leukaemia, aggressive NK-cell leukaemia, adult T-cell lymphoma/leukaemia (ATLL), T-cell large granular lymphocytic (T-LGL) leukaemia and unspecified peripheral T-cell lymphoma. Cases with concurrent lymphoma, higher absolute leukaemic cell counts and elevated lactate dehydrogenase level carried a poorer prognosis. The survival was dichotomous, with a very poor prognosis for patients with T-LBL, T-cell prolymphocytic leukaemia, aggressive NK-cell leukaemia, ATLL in acute phase and unspecified peripheral T-cell lymphoma, while those with T-LGL leukaemia and ATLL in chronic phase had a favourable outcome.

Theoretical analysis of release kinetics of coated tablets containing constant and non-constant drug reservoirs.

A detailed theoretical analysis of drug release from a two-dimensional membrane-reservoir tablet into a sink is presented. An entire process of drug release was modeled including a phase of drug release from a constant reservoir followed by a phase of non-constant reservoir. Explicit theoretical solutions were obtained for the first time for the two phases and integrated seamlessly to describe a drug release process from a non-steady state to a steady state. The theoretical solutions were useful for the prediction of release kinetics and analysis of formulation variables as demonstrated by various examples including tablets with varying coating thickness, material properties, drug solubility and partition coefficient, anisotropy and temporal idiosyncrasies.

Differential regulation of endothelial cell adhesion, spreading, and cytoskeleton on low-density polyethylene by nanotopography and surface chemistry modification induced by argon plasma treatment.

Plasma treatment of polymer surfaces can modify the nanoscale roughness, wettability, and oxygen surface functionalities. However, how these modifications regulate cell behavior is not well understood. The objective of this investigation was to examine adhesion, spreading, and cytoskeleton of vascular endothelial cells seeded on low-density polyethylene surfaces modified by Ar plasma. In the absence of serum, adhesion and spreading of the cells and actin filament assembly were enhanced by high-energy Ar plasma-induced hydrophilicity and formation of C-O groups at the surface. Although serum increased cell adhesion and spreading on untreated surfaces for a relatively short period, this behavior was not stable for a long time. In contrast to the untreated polymer surfaces, serum suppressed cell adhesion and spreading on the plasma-treated surfaces. The preadsorption of albumin from the bovine serum on the polymer surfaces inhibited cell adhesion and spreading. Results demonstrate the differential effects of Ar plasma-induced surface modifications on endothelial cell behavior and provide insight into complex interactions among polymer surfaces, adsorbed proteins, and cells. The findings of this study have significant implications in surface engineering for vascular repair.

Intracranial epidermoid cyst with hemorrhage: MR imaging findings.

We present a case of a 28-year-old woman with a cerebellopontine angle and prepontine cistern epidermoid cyst with unusual signal intensity. She presented with cranial nerve neuropathy and unsteady gait. MR imaging showed a tumor mass with central area of hemorrhage and a focal area of heterogeneous signal intensity with spotty enhancement, which correlated histologically to old blood in a cystic lumen and granulation of a cystic wall, with a large area of hemorrhage and mild vascularity.

Follow-up of bilateral subthalamic deep brain stimulation for Parkinson's disease.

PURPOSE: To demonstrate the effects of bilateral subthalamic deep brain stimulation (STN-DBS) in the treatment of Parkinson's disease (PD) after 4-45 months' follow-up. METHOD: Between 04/01 and 12/04, 46 PD patients were operated on with bilateral STN-DBS. All of them were evaluated with Unified Parkinson's Disease Rating Scale (UPDRS) parts II-V before surgery and 4-45 months after surgery. The amelioration of miscellaneous symptoms and decrease of medication dose, respectively, were compared. Main side effects were observed. FINDINGS: After surgery, both the score of activities of daily living (ADL) and the UPDRS motor score decreased significantly (p < 0.001). Among the PD symptoms, tremor was improved best. Rigidity, bradykinesia, axial symptoms, facial expression and dyskinesia were all improved, although to a lesser extent, while speech was not improved. Medication dose was decreased significantly (p < 0.001). According to the time of follow-up, 4 groups were classified (4-12 months, 13-24 months. 25-36 months and 37-45 months group). ADL, UPDRS motor score and dyskinesia subscore improvement were compared among these groups. No significant difference existed. No life threatening complications occurred. Main side effects included hypophonia, dyskinesia, confusion, depression. CONCLUSIONS: Bilateral STN-DBS is a satisfying surgical method for the treatment of advanced PD. It can improve the cardinal PD symptoms up to 45 months. Complications and side effects were rare and usually temporary or reversible.

Modeling of dispersed-drug release from two-dimensional matrix tablets.

A mathematical model was developed and analytical solutions were obtained for dispersed-drug release from two-dimensional matrix tablets in a perfect sink. This model can be used to describe kinetics of solute release from matrices with isotropic or anisotropic properties. Moving boundaries of dispersed-drug in both radial and axial directions and release kinetics were predicted by the model. Various factors influencing release kinetics were analyzed including the ratio of initial solute loading (C0) to solute solubility (Cs), the anisotropy of the matrix and the aspect ratio of tablet radius to the half-thickness. The model is also applicable to 1-D planar or 1-D cylindrical geometries when R/H is larger than 100 or smaller than 0.01.

Theoretical analysis of drug release into a finite medium from sphere ensembles with various size and concentration distributions.

Release kinetics for heterogeneous sphere ensembles with a dissolved drug, i.e., initial drug loading below or equal to the drug solubility in the matrix, in a finite external medium was modeled with consideration of heterogeneity among and within spheres. Numerical solutions were obtained using the finite element method for sphere ensemble with normal or log-normal distribution of particle size or initial drug loading among spheres. Exact series solutions were derived for ensembles with various initial loading distributions within spheres, namely linear, quadratic, sigmoidal and uniform distribution, using their mean or average radii. Simplified solutions retaining only one term of the series for non-uniform distributions and three terms for uniform distribution were suggested because of their good approximation to the exact solution. The results of finite element analysis showed that the release rate of an ensemble decreased with increasing standard deviation of particle size. Using weight-average radii in the exact solution gave a prediction of release profile closer to that from the actual size distribution than using mean radii. The three non-uniform loading patterns within spheres all showed reduced initial burst and release rate, leading to more steady release rates than uniform loading, among which the sigmoidal distribution offered the best near-zero order release. Non-uniform initial loading among spheres seemed to have insignificant influence on the release profiles. The volume ratio of liquid to a sphere ensemble played an important role in release kinetics. The derived analytical solutions are applicable to multiple spheres or a single sphere in a finite medium or in a perfect sink.

Expression of mutant nuclear beta-catenin correlates with non-invasive hepatocellular carcinoma, absence of portal vein spread, and good prognosis.

beta-catenin has functions both in the cadherin-mediated cell adhesion system and in the signalling pathway that mediates dorsal axis patterning in the embryo; it has been shown to be aberrantly expressed or mutated in diverse types of human tumour, but the biological significance of this remains to be clarified. To elucidate the clinical implications of aberrant beta-catenin expression and the potential differences between mutant and wild-type beta-catenin protein expression in hepatocellular carcinoma (HCC), the protein expression was analysed by immunohistochemical staining, supplemented by the analysis of gene mutation. Among 372 unifocal primary HCCs, beta-catenin was detected in the tumour cell membrane alone in 272 tumours (group A) and also in the nuclei in 100 (group B). In group A, 148 tumours had decreased beta-catenin expression, but the reduction did not correlate with invasion or prognosis. When compared with group A, however, group B had significantly lower frequencies of hepatitis B surface antigen carrier (p=0.015), and alpha-fetoprotein elevation (p=0.0003), but more often had non-invasive HCC (p<0.001) and better survival (p=0.01). Nuclear beta-catenin expression strongly correlated with mutation of the gene (p<0.00001). In group B, HCC with mutant nuclear beta-catenin correlated positively with non-invasive (stage 1) tumour and inversely with portal vein tumour thrombi (stage 3 HCC), and had significantly better 5-year survival, p<0.001 and p<0.0003, respectively. These results suggest that beta-catenin mutation plays an important role in the tumourigenesis of a subset of HCC of good prognosis, and that mutant and wild-type nuclear beta-catenin proteins are not functionally equivalent.

Cytosol vascular endothelial growth factor in endometrial carcinoma: correlation with disease-free survival.

OBJECTIVE: The aim of this study was to evaluate whether vascular endothelial growth factor (VEGF) could be a marker for disease-free survival in endometrial carcinoma patients. METHODS: Fifty-three patients with endometrial carcinoma undergoing surgery were enrolled. Clinical and pathologic items were recorded. Cytosol VEGF was quantified by enzyme immunoassay. The microvessel density (MVD) of the excised tumors was immunohistochemically assessed. The relationship among MVD, cytosol VEGF concentration of the tumor tissues, and clinicopathologic parameters was analyzed. The risk factors influencing clinical outcome were tested. RESULTS: Higher cytosol VEGF concentrations and MVD values were noted in tumors with advanced stage (more than stage I) (917 versus 125 pg/mg, P = 0.03; 94.1 +/- 37.8 versus 60.8 +/- 38.9, P = 0.008), lymphovascular emboli (917 versus 102 pg/mg, P = 0.001; 94.4 +/- 33.2 versus 62.4 +/- 40.7, P = 0.009), and lymph node metastasis (1032 versus 95 pg/mg, P < 0.001; 116.5 +/- 30.8 versus 56.7 +/- 33.3, P < 0.001). The cytosol VEGF and MVD showed a positive linear correlation (VEGF versus MVD, r = 0.41, P = 0.003). Grade 3 tumor and overexpressed cytosol VEGF (> 800 pg/mg) are independent risk factors for recurrence. There was a trend that patients with grade 1 or 2 tumors and normal-expressed VEGF had the highest probability of disease-free survival, and patients with grade 3 tumors and overexpressed cytosol VEGF had the poorest probability of disease-free survival. CONCLUSIONS: Cytosol VEGF had a good correlation with the disease progression and metastasis in endometrial carcinoma, and it might also be an independent prognostic factor for disease-free survival of endometrial carcinoma patients.

Angiogenesis of endometrial carcinomas assessed by measurement of intratumoral blood flow, microvessel density, and vascular endothelial growth factor levels.

OBJECTIVE: To evaluate the relationship between blood flow in the tumor assessed by color Doppler ultrasound, microvessel density, and vascular endothelial growth factor levels in endometrial carcinoma. METHODS: Forty-nine patients undergoing surgery for endometrial carcinoma were enrolled. Transvaginal color Doppler ultrasound was performed preoperatively and the lowest resistance index (RI) in the tumor was recorded for analysis. Vascular endothelial growth factor in the tumor was quantified by enzyme immunoassay. The microvessel density of the excised tumor was assessed immunohistochemically. The relationships between the corresponding RI, microvessel density, and vascular endothelial growth factor level of the tumor tissues and clinical and pathologic parameters were analyzed. RESULTS: Significantly lower RIs were noted in tumors of stage II or greater (0.37 compared with 0.50, P <.001), of high histologic grade (grade 3) (0.34 compared with 0.49, P =.004), with deep myometrial invasion (one-half depth or greater) (0.39 compared with 0.49, P =.002), with lymphovascular emboli (0.38 compared with 0.49, P <.001), or with lymph node metastasis (0.30 compared with 0.49, P <.001) compared with stage I tumors and tumors of histologic grade 1 or 2, with superficial myometrial invasion, without lymphovascular emboli, or with no lymph node metastasis. Increased vascular endothelial growth factor levels and microvessel density (x200 field) also were detected in tumors of stage II or greater (975 compared with 129 pg/mg, P =.014; and 88 compared with 61, P =.018, respectively), with lymphovascular emboli (1138 compared with 120 pg/mg, P =.002; and 86 compared with 63, P =.023), or with lymph node metastasis (1011 compared with 95 pg/mg, P <.001; and 98 compared with 61, P =. 019). Resistance index, microvessel density, and vascular endothelial growth factor levels in the tumor showed linear correlations (RI compared with microvessel density: r = -.32, P =. 03; RI compared with vascular endothelial growth factor levels: r = -.40, P =.004; microvessel density compared with vascular endothelial growth factor levels: r =.36, P =.011). CONCLUSION: Blood flow assessed by color Doppler ultrasound has histologic and biologic correlations with angiogenesis and vascular endothelial growth factor levels and might play an important role in predicting tumor progression and metastasis in endometrial carcinoma.

Beta-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis.

To better understand the role of beta-catenin mutation in hepatocellular carcinoma (HCC), we correlated the gene mutation with hepatitis virus B (HBV) and hepatitis virus C (HCV) status and the clinicopathological features in 366 patients with resected primary unifocal HCC. beta-Catenin mutations were also analyzed in 55 patients with multifocal HCC (68 tumors). Of the whole series, 57 (13.1%) of 434 tumors examined had beta-catenin mutations, 34 occurred at the serine/threonine residues of the GSK-3beta region of beta-catenin. Outside the GSK-3beta phosphorylation site, codons 32 and 34 were two mutational hot spots (17 tumors). The non-HBV-related HCC that was predominantly HCV related had a higher frequency of mutation (P: < 0.00001) and more frequent mutations at codon 45 than HBV-related HCC. HBV-related HCC had a younger mean age (P: < 0.00001), and higher male-to-female ratio (P: < 0.003) and positive familial history of HCC (P: < 0.014). Among 366 unifocal HCCs selected for clinicopathological analysis, beta-catenin mutations were associated with grade I (P: = 0.005) and stage I and II HCC (P: < 0.0001), and a better 5-year survival rate (P: = 0. 00003). These findings suggest mechanisms for beta-catenin mutations differ between HBV-related and non-HBV-related HCCs, and that beta-catenin mutation is a favorable prognostic factor related to low stage. beta-Catenin mutation was associated with nuclear expression of the protein (P: < 0.00001), but we failed to detect point or large fragment deletion mutation in 39 HCCs with nuclear beta-catenin expression, presumably wild-type protein. HCCs expressing mutant nuclear beta-catenin had a better 5-year survival rate (P: < 0.007), suggesting that mutant and wild-type nuclear beta-catenin proteins are not functionally equivalent and deserve more studies for further clarification.

Choledochal cyst in infancy: a follow-up study.

From January 1980 to February 1997, 19 cases, 8 males and 11 females, of choledochal cyst were diagnosed before one year old. The majority of patients were diagnosed by ultrasonography before 6 months old (15/19; 79%), including two diagnosed prenatally. According to Todani's classification, type Ia was the most common (74%), followed by type Ic (26%). Fourteen patients underwent Roux-en-Y choledocho- or hepatico-jejunostomy and cyst excision, 3 patients underwent Kasai operation, and I patient underwent external biliary drainage only. The remaining one patient with Trisomy 18 anomaly refused operation. Four of the 10 patients in whom liver histologic examinations were performed, had liver cirrhosis. The follow-up period of these patients ranged from 6 months to 9 years, with a mean of 4.1 years. We divided these 19 cases into 2 groups, according to the presence or absence of biliary atresia. In the 7 infants with biliary atresia (37%), all presented with jaundice and alcoholic stool. Two patients died due to delayed presentation and surgery, both had liver cirrhosis. One patient is living with liver cirrhosis. Another patient was lost to follow-up, but frequent cholangitis was noted till 8 months old. The remaining 3 patients are living and well. In the 12 without biliary atresia, 9 patients are living and well. Two patients died, one due to Trisomy 18 anomaly and the other with delayed surgery and liver cirrhosis. One case was lost to follow-up. In summary: 1-) a possibility of the association of biliary atresia in infants with choledochal cyst should be carefully searched and considered as a unique group; 2) ultrasonography is a good diagnostic tool in choledochal cyst during prenatal or infancy period; 3) the mortality cases were characterized by prolonged bile stasis, biliary cirrhosis, delayed surgery, or multiple anomalies; 4) surgery should be performed as early as possible for those with persistent jaundice and light colored stools.

The possible use of colour flow Doppler in planning treatment in early invasive carcinoma of the cervix.

OBJECTIVE: To investigate the pathological significance of intra-tumoural blood flow signals detected by colour Doppler ultrasound and their association with angiogenesis in cervical carcinoma. DESIGN: A prospective cross-sectional study. SETTING: University hospital. POPULATION: One hundred and four women with Stage IB-IIA cervical carcinoma. METHODS: All women underwent radical hysterectomy and pelvic lymph node dissection. Transvaginal colour Doppler ultrasound was performed before surgery to search for arterial blood flow signals within the tumours. Tumours with a measurable intra-tumoural resistance index were defined as tumour with detectable blood flow and the others as tumour with undetectable blood flow. The microvessel density of the excised tumour was assessed immunohistochemically. The women's clinical and pathologic data were recorded. RESULTS: There were 60 tumours (58%) exhibiting detectable intra-tumoural blood flow signals. Tumours with detectable blood flow were larger, had deeper cervical stromal invasion, a higher incidence of parametrial invasion and pelvic lymph node metastases, and a higher microvessel density, when compared with those without detectable blood flow. Cervical cancers with deep cervical stromal invasion, parametrial invasion, and pelvic lymph node metastasis had higher microvessel density than those with superficial stromal invasion, no parametrial invasion, or no lymph node metastasis. Microvessel density correlated well with lymph node metastases and parametrial invasion by multiple regression analysis, while intra-tumoural blood signals only showed correlation with parametrial invasion. In the prediction of pelvic lymph node metastases and parametrial invasion, colour flow Doppler had a sensitivity of 0.80 and specificity of 0.48 in predicting lymph node metastases, and sensitivity of 0.91 and specificity of 0.57 in predicting parametrial invasion. CONCLUSIONS: The characteristics of blood flow signals in cervical carcinoma detected by colour Doppler ultrasound are associated with tumour angiogenesis and could reflect the likelihood of parametrial invasion and lymph node metastases in cervical carcinoma. The intra-tumoural blood flow signals might be used as a screening test in predicting parametrial invasion and pelvic lymph node metastases. These findings may be helpful in planning treatment for women with Stage I and II cervical carcinoma.

p27 expression as a prognostic factor of breast cancer in Taiwan.

p27Kip1 is a member of the Cip/Kip family of cyclin-dependent kinase inhibitors. It binds to a variety of cyclin/CDK complexes, inhibits kinase activity, and blocks the cell cycle. Absent or reduced p27 expression has been shown to be a significant predictor of poor survival in breast, colorectal, prostate, non-small cell lung and esophagus carcinomas. An immunohistochemical assay was performed on 169 patients with primary breast cancers to evaluate the biologic significance of p27 expression. Decreased p27 expression was significantly associated with high grade (P = 0.00025), negative estrogen receptor (P = 0.00004), and negative progesterone receptor (P = 0.0038) breast cancers. Univariate analysis reveals that p27 expression inversely correlated significantly with overall survival (P = 0.0001). By multivariate analysis, p27 predicted the overall survival independently (P = 0.0096). Our study indicates that p27 expression is an independent prognostic marker of breast cancer in Taiwan.

Differential expression of type 1 angiotensin II receptor mRNA and aldosterone responsiveness to angiotensin in aldosterone-producing adenoma.

Aldosterone secretion in most patients with aldosterone-producing adenomas (APAs) is typically unresponsive to angiotensin II stimulation (AII-unresponsive, AII-U). In some patients, however, plasma aldosterone increases in response to AII stimulation (AII-responsive, AII-R). This differential aldosterone responsiveness could be related to the levels of type 1 AII receptors (AT1R) in the APA. To test this hypothesis, plasma aldosterone levels in response to upright posture and/or sequential high- and low-salt diets were measured by radioimmunoassay in nine patients with APAs. AT1R mRNA levels in the adenomas were quantified by competitive reverse transcription-polymerase chain reaction and correlated to the cellular composition of the adenoma. Two patients were categorised as AII-R by an increase of plasma aldosterone greater than 50% over the baseline. The remaining seven patients who had blunted plasma aldosterone responses were classified as AII-U. Histologically, the AII-R APAs consisted predominantly of zona glomerulosa (ZG)-like cells (> 90%), while the AII-U APAs contained zona fasciculata (ZF)-like cells ranging from 28 to 72%. There was an inverse relationship between the levels of AT1R mRNA in the APA and the percentage of ZF-like cells in the adenoma (n = 9, r = 0.73, P < 0.05). In situ hybridisation findings demonstrated that AT1R mRNA was more uniform and intensive in ZG-like cells than in ZF-like cells. These results suggest that heterogenous aldosterone responsiveness to angiotensin in APAs is histologically dependent and related to the differential expression of AT1R mRNA in the adenoma.