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PubMed1977

Histopathologic review of lymphoma cases from the Southwest Oncology Group.

Lymphoma Pathology Panel and Repository (LPPR) review of pathologic material from 354 patients registered on Southwest Oncology Group clinical trials substantiated the diagnosis of Hodgkin's disease (Lukes-Butler classification) in 175 (94%) of 186 cases and the diagnosis of non-Hodgkin's lymphoma (Rappaport classification) in 162 (96%) of 168 cases. However, complete agreement (type and subtype) between institutional and LPPR review diagnoses was found in only 66% of confirmed cases of Hodgkin's disease and in only 58% of confirmed cases of non-Hodgkin's lymphomas. In 26 (16%) of 160 cases of non-Hodgkin's lymphoma, the initial interpretation of pattern (nodular vs diffuse) differed: 20 (25%) of 81 nodular lymphomas had been thought to be diffuse and 6 (8%) of 79 diffuse lymphomas had been diagnosed as nodular. The frequency with which initial diagnoses were confirmed on LPPR review was highest for three subtypes of lymphoma: nodular sclerosis Hodgkin's disease (88%), diffuse histiocytic lymphoma (86%), and nodular lymphocytic lymphoma (78%); rates of confirmation for all other subtypes ranged from 13-50%. The results of this analysis emphasize the necessity of having pathologic review of all cases entered on major lymphoma studies so that comparability of cases can be assured and the results of those studies placed in proper perspective.

Hodgkin Disease↗

PubMed2005

Frozen section diagnosis in pediatric surgical pathology: a decade's experience in a children's hospital.

CONTEXT: Intraoperative consultations, including frozen sections (FSs), are essential for patient care and are a key quality component in anatomic pathology. Little data exists about the use, frequency, and type of discrepancies and deferral rates of FS diagnoses in pediatric and adolescent surgical pathology. OBJECTIVE: The purpose of this study was to analyze indications, discrepancies, and deferrals for all FSs performed at a children's hospital during a 10-year period. DESIGN: All FSs for 1995-2004 were reviewed for indications, discrepancies, deferred diagnoses, and turnaround time. Discrepancies were categorized into major and minor subtypes according to potential impact on patient care. RESULTS: A total of 35,611 surgical pathology cases were accessioned, with 2839 intraoperative consultations, which included 2783 FSs and 56 nonmicroscopic consultations. Most frequent indications included questions related to neoplasms (tumor detection, specimen adequacy, triage, classification, and margins) and suspected Hirschsprung disease. In these consultations, 115 discrepancies (4%) were identified, of which 7 (0.2%) were major, with potentially significant clinical impact, and 108 (3.9%) were minor. The major discrepancies included tumor, ganglion cell, or organism detection. The minor discrepancies involved sampling error, reclassification of benign or malignant neoplasms without clinical consequences, tumor typing or grading, and ganglion cell identification without clinical impact. Deferrals in 718 FSs (25% deferral rate) included tumor classification from generic to specific, identification of organisms, and evaluation of lymph node biopsies for lymphoma. Turnaround time exceeded 20 minutes in 403 cases (14%). CONCLUSIONS: The FS rate of 7.8% overall and 5% of surgical pathology cases is similar in children's and general hospitals. The major discrepancy (discordance) rate is lower, which may reflect the different indications for FS in children and adolescents. Evaluation of colonic biopsies for ganglion cells is a diagnostic pitfall. The deferral rate of 25% reflects the definition of a deferred diagnosis. Traditional definitions of deferred and discordant FS diagnoses should be refined to reflect the increasing use of adjunct techniques, especially in tumor classification. These findings emphasize that, in children and adolescents, most FSs are performed for tumor classification, triage, detection, and specimen adequacy, and for possible Hirschsprung disease. In children and adolescents, FSs are used infrequently to identify normal or unknown tissue, to analyze a lesion in a radiographically directed specimen, or to detect lymph node metastases. The differences in pediatric and adolescent FS indications and use underscore the importance of focused education in pediatric surgical pathology.

Frozen Sections↗

PubMed1997

Primary carcinomas of the urethra.

Urethral carcinomas are rare, and information reported in the literature is relatively limited. In this review, the authors present separate discussions on the pathology of carcinomas occurring in men and women with emphasis on the diverse histological subtypes. Because tumor type and prognosis correspond to anatomic location, normal anatomy and histology have been given due consideration. Of particular note in the recent literature is an expanded experience with clear cell carcinoma, a distinctive tumor primarily of the female urethra that has generated considerable interest with respect to its prognosis and relationship to urethral diverticulum. The authors use this review to illustrate several features of the pathology of these neoplasms synthesize the literature, and place into perspective the clinical, pathological, and prognostic features.

Adenocarcinoma, Clear Cell↗

PubMed1998

The family of sodium-dependent glutamate transporters: a focus on the GLT-1/EAAT2 subtype.

The acidic amino acids, glutamate and aspartate, are the predominant excitatory neurotransmitters in the mammalian CNS. Under many pathologic conditions, these excitatory amino acids (EAAs) accumulate in the extracellular fluid in CNS and the resultant excessive activation of EAA receptors contributes to brain injury through a process known as 'excitotoxicity'. Unlike many other neurotransmitters, there is no evidence for extracellular metabolism of EAAs, rather, they are cleared by Na+-dependent transport mechanisms. Therefore, this transport process is important for ensuring crisp synaptic signaling as well as limiting the excitotoxic potential of EAAs. With the cloning of five distinct EAA transporters, a variety of tools were developed to characterize individual transporter subtypes, including specific antibodies, expression systems, and probes to delete/knock-down expression of each subtype. These tools are beginning to provide fundamental information that has the potential to impact our understanding of EAA physiology and pathophysiology. For example, biophysical studies of the cloned transporters have led to the observation that some subtypes function as ligand-gated ion channels as well as transporters. With these reagents, it has also been possible to explore the relative contributions of each transporter to the clearance of extracellular EAAs and to begin to examine the regulation of specific transporter subtypes. In this review, an overview of the properties of the transporter subtypes will be presented. The evidence which suggests that the transporter, GLT1/EAAT2, may be sufficient to explain a large percentage of forebrain transport will be critically reviewed. Finally, the studies of regulation of GLT-1 in vitro and in vivo will be described.

ATP-Binding Cassette Transporters↗

PubMed2026

Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer's disease.

Myeloid cells, including microglia and perivascular macrophages, are central to Alzheimer's disease (AD) neurobiology, yet their role remains incompletely understood. We profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 donors spanning the lifespan and showing varying degrees of AD neuropathology. We delineated six subclasses comprising 13 transcriptionally distinct subtypes and identified adaptive changes associated with aging and AD progression. Here we show that a disease-associated microglial subtype, characterized by elevated GPNMB expression and enriched for polygenic AD risk, expands with AD pathology and shows increased phagocytic activity. We identify MITF as an upstream regulator required to maintain this microglial state. Cell-cell interaction analyses prioritize APOE-SORL1 and APOE-TREM2 signaling pairs associated with disease progression. Using human and mouse models, we demonstrate that the neuroprotective effects of this microglial subtype depend on TREM2. These findings provide mechanistic insights into myeloid cell function in aging and AD, aiding therapeutic discovery.

Humans↗

PubMed2000

Pathology of small vessel stroke.

Disease of small intracerebral vessels is widely assumed to be responsible for the majority of small, deep-seated (lacunar) infarcts and primary intracerebral haemorrhages. Our present, limited understanding of the pathogenesis of these stroke subtypes, which together constitute up to one-third of all strokes, is based on a limited number of detailed pathology studies, supported by clinical, risk factor and imaging data. Further progress using these traditional approaches has been prevented by a variety of largely technical obstacles. It is suggested that advances in our understanding of the genetic basis of established and new animal stroke models, in turn linked to more focused human genetic stroke surveys, may hold the key to further insights.

Cerebral Hemorrhage↗

PubMed1997

Endothelin-induced calcium signaling and secretion in chief cells and fibroblasts from pathological human parathyroid glands.

Endothelins (ETs) are 21 amino acid peptides with vasoactive and mitogenic properties. The three isopeptides (ET-1, -2, and -3) and their receptors (E1A and ETB subtypes) display expression in numerous tissues and possibly mediate autocrine/paracrine actions. The present investigation shows that ET-1 triggers biphasic increases of the concentration of cytoplasmic Ca2+ ([Ca2+]i) in pathological human parathyroid cells. Both the peak and sustained [Ca2+]i increase, as well as the proportion of responding cells, are dose-dependent in the 10(-10)-10(-7) mol/L range of ET-1. In absence of external Ca2+, the ET-1-induced [Ca2+]i peak is attenuated. ET-3 has no effect on [Ca2+]i indicating functional dominance of the ETA receptor subtype. ET-1 (10 nmol/L) lowers parathyroid hormone secretion in 0.5 mmol/L but not in higher external Ca2+ concentrations, and parathyroid cell ET release is inhibited by increases of external Ca2+. Fibroblasts overgrowing the parathyroid chief cells during monolayer culture respond to ET-1 with biphasic [Ca2+]i increases or repetitive [Ca2+]i spikes, but show no response to elevation of external Ca2+. These findings imply that ET secretion and ET receptor expression may constitute an autocrine/paracrine mechanism in the regulation of human PTH secretion.

Adenoma↗

PubMed2004

Clinical and pathological characteristics of four Korean patients with limb-girdle muscular dystrophy type 2B.

Limb-girdle muscular dystrophy type 2B (LGMD2B), a subtype of autosomal recessive limb-girdle muscular dystrophy (ARLGMD), is characterized by a relatively late onset and slow progressive course. LGMD2B is known to be caused by the loss of the dysferlin protein at sarcolemma in muscle fibers. In this study, the clinical and pathological characteristics of Korean LGMD2B patients were investigated. Seventeen patients with ARLGMD underwent muscle biopsy and the histochemical examination was performed. For the immunocytochemistry, a set of antibodies against dystrophin, alpha, beta, gamma, delta-sarcoglycans, dysferlin, caveolin-3, and beta-dystroglycan was used. Four patients (24%) showed selective loss of immunoreactivity against dysferlin at the sarcolemma on the muscle specimens. Therefore, they were classified into the LGMD2B category. The age at the onset of disease ranged from 9 yr to 33 yr, and none of the patients was wheelchair bound at the neurological examination. The serum creatine kinase (CK) was high in all the patients (4010-5310 IU/L). The pathologic examination showed mild to moderate dystrophic features. These are the first Korean LGMD2B cases with a dysferlin deficiency confirmed by immunocytochemistry. The clinical, pathological, and immunocytochemical findings of the patients with LGMD2B in this study were in accordance with those of other previous reports.

Adolescent↗

PubMed2004

Dynamic MR imaging: value of differentiating subtypes of peripheral small adenocarcinoma of the lung.

PURPOSE: To determine the utility of dynamic magnetic resonance imaging (MRI) in the differential subtyping of small adenocarcinomas of the lung. MATERIALS AND METHODS: Twenty-nine pathologically diagnosed peripheral adenocarcinomas (less than 20 mm in diameter) underwent dynamic contrast-enhanced MRI. Maximum relative enhancement ratio, slope of enhancement, and corrected start time of enhancement were calculated from signal intensity-time curve of pulmonary lesion for each subject, and were statistically compared among bronchioloalveolar carcinoma (BAC) group (7 cases), mixed BAC group (10 cases), and adenocarcinoma group (12 cases). RESULTS: Maximum relative enhancement ratio (P<0.001) and slope of enhancement (P<0.001) of BAC group were significantly higher than those of mixed BAC and adenocarcinoma groups. Start times of BAC group were significantly earlier than those of mixed BAC (P=0.0001) and adenocarcinoma groups (P<0.0001). Adapting the thresholds values of MR indexes from the positive tests, sensitivity, specificity, positive predictive value, negative predictive value and accuracy for differentiating BAC from other subtypes were 85.7, 100.0, 100.0, 95.7, and 96.6%, respectively. CONCLUSIONS: Dynamic MRI is useful for differentiating subtypes of small peripheral adenocarcinoma.

Adenocarcinoma↗

PubMed2004

Clinical and pathologic features of invasive micropapillary carcinoma.

BACKGROUND: Invasive micropapillary carcinoma(IMC)of the breast is a rare subtype of breast carcinoma that has an extremely high incidence of lymph node metastases and poor clinical outcome. This histological subtype of breast carcinoma has remained unclear due to the rarity of cases. Many questions exist on the clinicopathological significance of this subtype, especially regarding prognosis. METHODS: We reviewed all 671 cases of primary breast carcinoma that were surgically resected at our institute between 1990 and 2004. Of these, 27 cases of invasive ductal carcinoma of the breast with a pure or partial micropapillary component were reported. The cases were analyzed using various parameters, including age at presentation, tumor size, tumor grade, presence of lymphatic invasion, and axially lymph node status. RESULTS: The patients' age at presentation ranged from 31 to 74 years (mean 52.4 years). Tumor size ranged from 0.7 to 10 cm (mean 4 cm). 88.9% (24 of 27) of the cases had lymphatic invasion. Of cases who underwent with axillary dissection, 66.6% (18 of 27) had positive lymph nodes. Clinical follow up data were available for 17 cases with IMC for 1 to 72 months. Among these, 10 patients died from breast carcinoma within 5 years. CONCLUSION: While our series is too small to make conclusions about the behavior of IMC, the difference in 6-year survival rate between the patients with IMC and those with breast carcinoma in general was statistically significant. Recognition of this distinctive and aggressive variant of infiltrating carcinoma is important because of its poor prognosis and high incidence of lymph node metastases.

Adult↗

PubMed2005

Clinical and pathologic factors associated with survival in young adult patients with fibrolamellar hepatocarcinoma.

BACKGROUND: Fibrolamellar Carcinoma (FLC), a subtype of hepatocellular carcinoma (HCC), is a rare primary hepatic malignancy. Several aspects of the clinic features and epidemiology of FLC remain unclear because most of the literature on FLC consists of case reports and small cases series with limited information on factors that affect survival. METHODS: We did a retrospective analysis of the clinical and histological characteristics of FLC. We also determined the rate of cellular proliferation in biopsies of these tumors. We assessed whether these variables were associated with survival. RESULTS: We found 15 patients with FLC out of 174 patients with HCC (8.6%). Between patients with these neoplasms, we found statistically significant survival, age at onset, level of alpha fetoprotein, and an earlier stage of the disease. The 1, 3 and 5 year survival in patients with FLC was of 66, 40 and 26% respectively. The factors associated with a higher survival in patients with FLC were age more than 23 years, feasibility of surgical resection, free surgical borders, absence of thrombosis or invasion to hepatic vessels and the absence of alterations in liver enzymes. The size of the tumor, gender, cellular proliferation and atypia did not affect the prognosis. CONCLUSION: We concluded that FLC patients diagnosed before 23 years of age have worse prognosis than those diagnosed after age 23. Other factors associated with worse prognosis in this study are: lack of surgical treatment, presence of positive surgical margins, vascular invasion, and altered hepatic enzymes.

Adolescent↗

PubMed2001

Bronchioloalveolar carcinoma: clinical, radiographic, and pathological findings. Surgical results.

BACKGROUND: Bronchioloalveolar carcinoma (BAC) remains one of the most controversial of lung cancer subtypes. METHODS: From 1980 to 1998, 374 resected patients for NSCLC were followed up in our department. Of the 147 cases histologically defined as adenocarcinoma, 34 were pure BAC. The records of these 34 patients were retrospectively reviewed in order to evaluate patient and tumor characteristics and to identify which variables had a prognostic impact on survival and recurrence rate. RESULTS: Patient age, sex, smoking habits and symptoms were not differentiating characteristics when related to radiographic presentation or to natural history. Mucinous cell-type (23.6% of cases) was more frequent with non-smokers, presence of a single nodule or mass and stage I. Favorable characteristics were: a) the prevalence of stage I and N0 cases (59% and 76.7% of cases, respectively) with a mean survival time of 66 and 77 months, respectively; and b) the radiographic presentation of a solitary pulmonary nodule or mass (76.4% of cases), that, independently of nodal involvement, showed a higher mean survival time (62 months). Independently significant adverse prognostic factors were: stage II-IV, lymph node involvement, and patient age over sixty years. The radiographic presence of multiple or satellite nodules was related to a significantly adverse prognosis (mean survival time: 18 months) by univariate analysis; this was not confirmed by multivariate analysis. CONCLUSIONS: In our experience BAC was the NSCLC subtype more frequently associated with a good outcome after resection; surgery should not to be denied also in patients with multiple nodules, when under sixty years of age and no lymph node involvement.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1997

Serological diagnosis of chlamydial abortion in sheep and goats: comparison of the complement fixation test and an enzyme-linked immunosorbent assay employing solubilised proteins as antigen.

A new ELISA for antibodies against chlamydial abortion of ewes which uses detergent solubilised proteins (dsp) of Chlamydia psittaci as antigen (Anderson, I.E., Herring, A.J., Jones, G.E., Low, J.C., Greig, A., 1995. Development and evaluation of an indirect ELISA to detect antibodies to abortion strains of Chlamydia psittaci in sheep sera. Vet. Microbiol., 43, pp. 1-12] was compared with the complement fixation test (CFT) in screening 1000 ovine and caprine sera obtained from selected flocks/herds ('flocks') and submitted to a veterinary diagnostic laboratory. Fifteen of the 17 'flocks' had a history of abortion while the remaining two did not and were classified as 'negative flocks'. Infection with Chlamydia was confirmed during the study period in five 'flocks' using direct immunofluorescence and the modified Ziehl Neelsen stain on pathological material. The dspELISA and CFT identified 37 and 45 positive sera on 158 samples tested from these 'flocks'. Chlamydia antibodies were not detected in one of the two negative flocks, in two other flocks where the cause of abortion was undetermined and in three flocks in which the causes of abortion were diagnosed as Listeriosis and/or Salmonellosis. One of the 'negative flocks' yielded two positive reactors by CFT and five by dspELISA, suggesting infection with a cross-reactive subtype of C. pecorum. Of the five 'flocks' in which a definitive diagnosis from pathological material was not possible, four were positive by both serological tests, suggesting that the abortions were due to Chlamydia. The fifth flock, though negative by dspELISA and marginally positive in two samples by CFT, had experienced confirmed chlamydial abortions in previous lambing seasons, but culling and tetracycline treatment have prevented further abortions in the study period. Overall, the proportions of samples positive by CFT and dspELISA were similar (9.1% and 8.8%). These studies confirmed the value of the dspELISA as a screening test for chlamydial abortion. Furthermore, the dspELISA compared to the CFT is easier to perform, does not require reagent titration at each testing and uses automated assessment of results.

Abortion, Veterinary↗

PubMed1990

Re-evaluation of fibroblasts and fibroblast-like cells.

Scanning electron microscopic observations of connective tissue cells show a new aspect of the nature of fibroblasts, and the subsequent broad survey of references makes clear that fibroblasts of many tissues have various features which are regarded as atypical of fibroblasts, and at the same time that various connective tissue cells in different organs have features typical of fibroblasts. Both morphological and functional features of fibroblasts are more or less common to those of fibroblast-like cells, and differences among these cells are quantitative rather than qualitative. Therefore, it is almost impossible to set clear-cut criteria for distinguishing genuine fibroblasts from a large population of fibroblast-like cells. The majority of cells sharing features of fibroblasts, if not all, seem to belong to the same population of cells. They are probably adapted to special functional needs in their own micro-environment that are peculiar to local or pathological or experimental conditions. It is proposed to categorize these cells into subtypes depending on their main functions: 1, fibrogenesis; 2, tissue skeleton or barrier; 3, intercellular communication system; 4, gentle contractile machinery; 5, endocrine activity; and 6, vitamin A-storing. Re-evaluation of fibroblasts and fibroblast-like cells is required to facilitate their better understanding.

Animals↗

PubMed2005

[Animal models of parkinsonism].

Research into the pathophysiology of Parkinson's disease has been rapidly advanced by the development of animal models. Initial models were developed by using toxins that specifically targeted dopamine neurons, the most successful of which used 6-hydroxydopamine in rats and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice and primates. Their combination with specific striatal toxins, such as quinolinic acid or 3-nitropropionic acid, has led to the development of experimental models replicating the salient pathological and clinical features of multiple system atrophy of the striatonigral degeneration subtype both in rodents and primates. More recently, the identification of alpha-synuclein gene mutations in rare familial cases of Parkinson's disease has led to the development of alpha-synuclein knock-out and transgenic animals. We conclude that the use and improvement of both phenotypic and genetic models can significantly speed progress toward understanding the pathophysiology of these devastating diseases and finding innovative cures.

Animals↗

PubMed2002

Correlation of clinical and pathologic features with outcome in patients with ductal carcinoma in situ of the breast treated with breast-conserving surgery and radiotherapy.

PURPOSE: Although breast-conserving surgery followed by radiotherapy (RT) has become a standard treatment option for patients with ductal carcinoma in situ of the breast, risk factors for ipsilateral breast tumor recurrence (IBTR) in these patients remain an active area of investigation. The purpose of this study was to evaluate the impact of clinical and pathologic features on long-term outcome in a cohort of DCIS patients treated with breast-conserving surgery plus RT. METHODS AND MATERIALS: Between 1973 and 1998, 230 patients with DCIS were treated with breast-conserving surgery plus RT at our institution. All patients were treated by local excision followed by RT to the breast to a total median tumor bed dose of 64 Gy. Adjuvant hormonal therapy was used in only 20 patients (9%). All available clinical, pathologic, and outcome data, including ipsilateral and contralateral events, were entered into a computerized database. The clinical and pathologic variables evaluated included detection method, mammographic appearance, age, family history, histologic subtype, presence of necrosis, nuclear grade, final margin status, and use of adjuvant hormonal therapy. RESULTS: As of December 15, 2000, with a median follow-up of 8.2 years, 17 patients had developed a recurrence in the ipsilateral breast, resulting in a 5- and 10-year IBTR rate of 5% and 13%, respectively. Contralateral breast cancer developed in 8 patients, resulting in a 10-year contralateral recurrence rate of 5%. Patient age, family history, histologic subtype, margin status, and tumor grade were not significantly associated with recurrence on univariate analysis. A significantly higher rate of local relapse was observed in patients with the presence of necrosis. The 10-year relapse rate was 22% in 88 patients with necrosis compared with 7% in 142 patients without necrosis (p <0.01). In multivariate analysis, the presence of necrosis remained a significant predictor of local relapse. No breast relapses occurred among the 8 patients with positive margins, and three relapses developed among 21 patients with close margins. The rate of IBTR in those with close/positive margins did not differ from the rate in those with negative or unknown margins. It is also notable that none of the 20 patients treated with adjuvant tamoxifen had developed IBTR or a contralateral event to date, although the follow-up on this group was still too short to reach significance. CONCLUSION: In this cohort of uniformly treated patients with a relatively long follow-up, the presence of necrosis was a significant predictor of local relapse. However, positive or close margin status was not a significant predictor of local relapse. Although none of the patients receiving tamoxifen had a recurrence in the ipsilateral or contralateral breast, longer follow-up is required to assess the effect of tamoxifen on these end points.

Adult↗

PubMed2001

Nicotinic receptor subtypes in human brain related to aging and dementia.

Neuronal nicotinic receptors are attracting increasing interest, beyond their role in relation to tobacco use, in the areas of human brain aging and disorders associated with dementia. Of the different receptor subtypes in the mammalian brain, many decline with normal aging in several different areas, including particularly cerebral cortex and hippocampus. There are further select subtype changes in the two most common forms of dementia in the elderly: Alzheimer's disease and dementia with Lewy bodies. The alpha4 subunit is most extensively reduced in the cortex in Alzheimer's disease, reflected in the loss of the high affinity binding site. There are also reductions in the low affinity binding site (alpha-bungarotoxin binding) in the thalamus in both disorders, which are likely to reflect the loss of the homomeric (most commonly alpha7) receptor subtype. Correlations exist between some of these receptor abnormalities and clinical and pathological features of the diseases. Targeting such receptors is a current therapeutic objective.

Aging↗

PubMed1996

The renin-angiotensin system in the rabbit eye.

We analyzed the components of the renin-angiotensin system (RAS) in ocular tissues of normal rabbit eyes and compared the results with those measured in rabbit eyes with proliferative vitreoretinopathy and ocular hypertension. Proliferative vitreoretinopathy was induced by injection of human platelets into the vitreous humor, and ocular hypertension was induced by injection of alpha-chymotrypsin into the posterior chamber. Angiotensinogen, renin, angiotensin converting enzyme (ACE), angiotensin II (Ang II), and Ang II receptors were assessed using conventional biochemical techniques. The vascularized tissues of normal eyes contained high renin and ACE activities concomitant with low concentration of angiotensinogen and Ang II. In general, in the ocular humors, the opposite was found. The Ang II receptor density was highest in the uveal tract [range 35-190 fmol/mg protein]. The AT1 receptor subtype predominated [> 80%]. The RAS was only minimally different in the two pathological models except that, in ocular hypertension, the renin activity in the uveal tract was reduced [-50%]. Also, the ratio of AT1 to AT2 receptors changed as compared to control, although the total receptor density remained unaltered. In conclusion, we present evidence for the presence of a complete local RAS in the rabbit eye, which is only marginally affected by the two pathological models studied.

Angiotensin II↗