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PubMed2006

Advances in the development of bradykinin receptor ligands.

Kinins are blood-derived local-acting peptides that elicit specific cellular effects via the stimulation of two related G protein coupled receptors. While the B(2)receptor subtype, constitutively expressed in various tissues, is believed to mediate most of the physiological actions of kinins in healthy conditions, the B(1) receptor, highly regulated during inflammation, has been associated with the sustained actions of these peptides in various pathological situations. Potent peptide and nonpeptide modulators of both kinin receptors have been produced as pharmacological tools and potential therapeutics over the last three decades. More recently, the accumulating evidence suggesting that B(1) receptor blockade could be useful for the treatment of pain and inflammatory disorders has led to a shift in drug development efforts toward the synthesis of orally bioavailable nonpeptide B(1) receptor antagonists. Nonpeptide ligands of either receptor subtype produced by several industrial organizations often possess significant structural commonalities that can lead to the definition of a pharmacophore, especially when the receptor docking models are compared. The field of kinin receptors ligands research has reached an exciting step of its history, as the near future will reveal whether these molecules are therapeutically beneficial in various human diseases. This review will concisely summarize our current understanding of the biology of kinins and their receptors, before discussing the recent medicinal chemistry developments and challenges that bring new kinin receptor ligands closer to clinical applications.

Animals↗

PubMed2001

[Malignant pleural mesothelioma].

Malignant pleural mesothelioma is a severe disease closely associated with asbestos exposure, at work or environmental. Its incidence has risen for some decades and it's expected to peak between 2010 and 2020. Up today, no treatment has been demonstrated as effective in influencing disease-related survival and the median prognosis ranges between 9 and 17 months after the diagnosis. The epithelial subtype of the disease seems to have a better prognosis when early diagnosed and treated with intrapleural immunotherapy or multimodality therapy. The diagnosis of the disease, often by exclusion, is obtained after macroscopic sampling of the pathological tissue, best accomplished by thoracoscopy, which also allows the intracavitary evaluation of the extension of the disease. Chemotherapy and radiotherapy alone didn't demonstrate any efficacy on the patient survival. For the early-stage disease (stage I) a therapeutic approach seems to be neoadjuvant intrapleural treatment using cytokines. For more advanced disease (stages II and III) resectability should be discussed with the thoracic surgeons and a multimodality treatment combining surgery, radiotherapy and chemotherapy should be proposed. This multimodality protocol has proved to be effective in patients with epithelial subtype, negative margins of resection and negative lymph nodes.

Humans↗

PubMed2005

The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions.

The VEGF (vascular endothelial growth factor) family and its receptors are essential regulators of angiogenesis and vascular permeability. Currently, the VEGF family consists of VEGF-A, PlGF (placenta growth factor), VEGF-B, VEGF-C, VEGF-D, VEGF-E and snake venom VEGF. VEGF-A has at least nine subtypes due to the alternative splicing of a single gene. Although the VEGF165 isoform plays a central role in vascular development, recent studies have demonstrated that each VEGF isoform plays distinct roles in vascular patterning and arterial development. VEGF-A binds to and activates two tyrosine kinase receptors, VEGFR (VEGF receptor)-1 and VEGFR-2. VEGFR-2 mediates most of the endothelial growth and survival signals, but VEGFR-1-mediated signalling plays important roles in pathological conditions such as cancer, ischaemia and inflammation. In solid tumours, VEGF-A and its receptor are involved in carcinogenesis, invasion and distant metastasis as well as tumour angiogenesis. VEGF-A also has a neuroprotective effect on hypoxic motor neurons, and is a modifier of ALS (amyotrophic lateral sclerosis). Recent progress in the molecular and biological understanding of the VEGF/VEGFR system provides us with novel and promising therapeutic strategies and target proteins for overcoming a variety of diseases.

Animals↗

PubMed2002

Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations.

Disease progression in multiple sclerosis occurs within the interface of glial activation and gliosis. This study aimed to investigate the relationship between biomarkers of different glial cell responses: (i) to disease dynamics and the clinical subtypes of multiple sclerosis; (ii) to disability; and (iii) to cross-validate these findings in a post-mortem study. To address the first goal, 51 patients with multiple sclerosis [20 relapsing remitting (RR), 21 secondary progressive (SP) and 10 primary progressive (PP)] and 51 neurological control patients were included. Disability was assessed using the ambulation index (AI), the Expanded Disability Status Scale score (EDSS) and the 9-hole PEG test (9HPT). Patients underwent lumbar puncture within 7 days of clinical assessment. Post-mortem brain tissue (12 multiple sclerosis and eight control patients) was classified histologically and adjacent sites were homogenized for protein analysis. S100B, ferritin and glial-fibrillary acidic protein (GFAP) were quantified in CSF and brain-tissue homogenate by ELISA (enzyme-linked immunosorbent assay) techniques developed in-house. There was a significant trend for increasing S100B levels from PP to SP to RR multiple sclerosis (P < 0.05). S100B was significantly higher in RR multiple sclerosis than in control patients (P < 0.01), whilst ferritin levels were significantly higher in SP multiple sclerosis than in control patients (P < 0.01). The S100B : ferritin ratio discriminated patients with RR multiple sclerosis from SP, PP or control patients (P < 0.05, P < 0.01 and P < 0.01, respectively). Multiple sclerosis patients with poor ambulation (AI > or =7) or severe disability (EDSS >6.5) had significantly higher CSF GFAP levels than less disabled multiple sclerosis or control patients (P < 0.01 and P < 0.001, respectively). There was a correlation between GFAP levels and ambulation in SP multiple sclerosis (r = 0.57, P < 0.01), and between S100B level and the 9HPT in PP multiple sclerosis patients (r = -0.85, P < 0.01). The post-mortem study showed significantly higher S100B levels in the acute than in the subacute plaques (P < 0.01), whilst ferritin levels were elevated in all multiple sclerosis lesion stages. Both GFAP and S100B levels were significantly higher in the cortex of multiple sclerosis than in control brain homogenate (P < 0.001 and P < 0.05, respectively). We found that S100B is a good marker for the relapsing phase of the disease (confirmed by post-mortem observation) as opposed to ferritin, which is elevated throughout the entire course. GFAP correlated with disability scales and may therefore be a marker for irreversible damage. The results of this study have broad implications for finding new and sensitive outcome measures for treatment trials that aim to delay the development of disability. They may also be considered in future classifications of multiple sclerosis patients.

Adult↗

PubMed1993

Primary mediastinal B-cell lymphoma with sclerosis: an aggressive tumor with distinctive clinical and pathologic features.

PURPOSE: To evaluate the clinical features of presentation, the morphologic and immunohistochemical pattern, the modality of spread, and the response to current treatments of patients with primary mediastinal B-cell lymphoma, a recently documented subtype of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty consecutive patients (14 males, 16 females; median age, 26 years) with primary mediastinal B-cell lymphoma with sclerosis were studied. RESULTS: The clinical aspects were largely homogeneous: 93% presented with chest symptoms of a rapidly enlarging mass of the anterior mediastinum; the tumor was bulky in 73%, and superior vena cava syndrome (SVCS) was present in 57%. Also, patients without SVCS symptoms showed subclinical venacaval compression at computed tomographic (CT) scan, for a total incidence of caval obstruction of 80%. Intrathoracic extension to adjacent organs was seen in 47% of patients. Despite its invasive behavior, only four patients showed extrathoracic spread at diagnosis. In 23 cases, the tumor presented with morphologic features that resembled follicular center-cell lymphomas. In seven, the neoplastic population was composed mainly of centrocyte-like cells with abundant clear cytoplasm not referable to any known B-cell lymphoma subtype. All cases showed huge sclerosis. Of 29 patients assessable for response, 16 (55%) achieved a complete response (CR): five of 14 (36%) treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and 11 of 15 (73%) treated with methotrexate plus leucovarin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) or etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) (P = .047). We could identify no clinical, biologic, or histopathologic features significantly correlated with response. After chemotherapy, 14 of 16 remitters received consolidation radiotherapy to the mediastinum. At 3 years, the actuarial survival rate is 38% for all cases and 72% for remitters. None of the 13 patients who did not achieve CR responded to salvage treatments. CONCLUSION: This study shows that primary mediastinal B-cell lymphoma with sclerosis is a distinctive subtype of NHL with unique clinicopathologic aspects and aggressive behavior. Prompt recognition and aggressive treatment may provide long survival in a good proportion of cases. However, a subset of patients is extremely refractory to first- and second-line treatment. Conventional prognostic factors seem inadequate to identify these very-poor-risk cases.

Adolescent↗

PubMed2001

Host ethnicity influences non-Hodgkin's lymphoma subtype frequency and Epstein-Barr virus association rate: the experience of a multi-ethnic patient population in Malaysia.

AIMS: The pattern of malignant lymphoma is known to vary in different populations. This study aims to elucidate the effect of ethnicity on subtype frequency of non-Hodgkin's lymphoma and EBV association rate. METHODS AND RESULTS: A total of 232 reconfirmed lymphoma cases in Malaysian patients were retrieved from the archives in the Department of Pathology, University Hospital, Kuala Lumpur. There were 24 (10%) Hodgkin's and 208 (90%) non-Hodgkin's lymphomas, 173 of the latter were in adult group (aged > or = 15 years). The ethnic composition were 41 Malays, 107 Chinese, 21 Indians and four none of the above. A male : female ratio of 2.4 : 1 was observed. Complete immunohistochemical studies in 158 cases revealed 36 (23%) T-cell, 121 (76%) B-cell and one (1%) null-cell phenotype. Seventy-five percent of the T-cell lymphomas were peripheral T/NK-cell types. Among the classifiable lesions, low-grade/indolent lymphomas constituted 17%: 2% were the lymphocytic subtype and 10% were follicular lymphomas. Approximately one-third of the follicular lymphomas occurred in Indian patients. The largest group of high-grade lymphoma was diffuse large B-cell type (46%), followed by peripheral T/NK-cell (18%). A predominance of NK/T-cell lymphomas occurred in Chinese (5/7), and all were EBV associated. Burkitt's lymphoma accounted for 5% (eight cases), all were Chinese males, with a 38% EBV-association rate. The frequency of EBV-associated B-cell lymphoma is three times more common in Chinese than Malays. The EBV positivity rate among lymphomas in ethnic Malay, Chinese and Indian patients was 5%, 15% and 22%, respectively, and in T- and B-cell lymphomas was 36% and 7%, respectively. CONCLUSIONS: This Malaysian series reveals differences in the subtype frequencies of non-Hodgkin's lymphomas and EBV association rate amongst patients of various ethnic groups residing in the same environment.

Adolescent↗

PubMed1999

Leukotrienes, leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma: an update. Part I: synthesis, receptors and role of leukotrienes in asthma.

Asthma is a chronic inflammatory disease associated with airflow obstruction. Airflow obstruction results from contraction of airway smooth muscle, mucosal oedema, increased secretion of mucus and infiltration of the airway wall by inflammatory cells, particularly eosinophils. Leukotrienes are thought to contribute to the pathophysiology of asthma. Leukotrienes are synthesised from arachidonic acid by a specific synthesis pathway whose key enzyme is 5-lipoxygenase. Cysteinyl leukotrienes (leukotrienes C4, D4 and E4) have been shown to mimic all the pathologic changes that are characteristic of asthma, whereas leukotriene B4 does not appear to exert biological properties relevant to asthma. Cysteinyl leukotrienes bind to two receptor subtypes: CysLT1 and CysLT2. Most of the biological properties of cysteinyl leukotrienes relevant to asthma are mediated through CysLT1 receptor stimulation.

Anti-Asthmatic Agents↗

PubMed1997

Phylogenetic analysis of the human papillomavirus type 2 (HPV-2), HPV-27, and HPV-57 group, which is associated with common warts.

Human papillomavirus types 2 (HPV-2), HPV-27, and HPV-57, are three closely related viruses within the phylogenetic supergroup formed by the remotely related genital papillomaviruses. In contrast to this phylogenetic association, these three viruses are most often found in common warts at nongenital sites, but also occasionally in genital warts and mucosal lesions of the nasopharyngeal cavity. We studied the genomic diversity of HPV sequences in skin warts presumably caused by these viruses. These biopsies were sampled from 75 patients living in Germany, Japan, or Singapore. Among 27 warts with HPV-2, we found seven new genomic variants and among 32 with HPV-57, eight new variants. In both cases, we did not detect the original prototype genomes. In contrast, 13 of 16 warts with HPV-27 contained the prototype genome, and only one new variant was found in three patients. We did not find variants clearly intermediate between any two types, although HPV-2 and HPV-27 are among the most closely related of the extent HPV types. We also did not detect novel HPV types, although the samples were examined with polymerase chain reaction protocols that would have detected remotely related HPVs. So we propose that the phylogenetic group formed by HPV-2, HPV-27, and HPV-57 has no or only very are additional members. One of the HPV-57 variants found, HPV-57-G44, was most likely identical to the subtype HPV-57b, previously proposed to be associated with nasal neoplasia, but found here frequently in common skin warts. Our publication establishes a foundation for pathological and phylogenetic comparisons of HPV types in skin warts.

Base Sequence↗

PubMed1991

Cytogenetic findings in typical and atypical meningioma.

Comparative pathological and karyotypic findings of a typical and an atypical meningioma in two different patients are presented. The chromosomal abnormalities observed appeared unique for the histopathological subtype of the tumor. Cytogenetic analysis of atypical meningioma has not previously been reported.

Adult↗

PubMedDate not supplied

Primary high grade malignant lymphoma of bladder.

Primary malignant lymphoma of bladder is one of the rarest extranodal site for lymphomas. Less than 100 cases have been reported so far. A history of chronic cystitis has been shown to be a preceding feature in many cases (40%) of primary bladder lymphoma. Most of the cases reported in the literature have a low-grade lymphoma including the subtypes of mucosa-associated lymphoid tissue. The diffuse large cell lymphoma is the most frequent type among the subtypes of high-grade bladder lymphomas. In this report, a case with high-grade primary malignant lymphoma of bladder is reported and the clinical, pathological aspects of diseases are reviewed.

Aged↗

PubMed2000

Cutaneous presentation of steroid responsive blastoid natural killer cell lymphoma.

CD56+ lymphomas derived from natural killer (NK) cell lineage are rarely encountered in Western populations and their clinical and pathological features have not been fully defined. The majority of reported cases are lymphomas of the nasal cavity, which are most commonly seen in Asia. A subtype of CD56+ lymphoma has recently been described (blastoid NK-cell lymphoma) which characteristically presents in older patients with cutaneous infiltrates and disease at other nodal and extranodal sites. We describe a case that correlates well with the clinicopathological features of blastoid NK-cell lymphoma. An unusual feature in our patient was that the cutaneous features of the lymphoma showed complete resolution shortly following commencement of oral steroid therapy.

Aged↗

PubMed2006

Biomarkers of response to preoperative chemoradiation in esophageal cancers.

To identify a panel of biomarkers that predicts response of esophageal cancers to preoperative chemoradiation, our group profiled the gene expression of pretreatment cancer biopsies from patients with esophageal cancer. Six (32%) of these patients had pathologic complete response. All cancers except one that achieved pathologic complete response (83%) clustered in one molecular type (type I), while cancers that achieved less than pathologic complete response with one exception clustered in another molecular type (type II). Activated NF-kappaB was significantly associated with aggressive pathology. These data indicate that expression analysis of a limited set of biomarkers selected from the list of genes that were differentially regulated between the two subtypes can increase predictive power, and suggest that esophageal cancer with activated NF-kappaB may result in poor treatment outcome.

Adenocarcinoma↗

PubMed2003

Peripheral T-cell lymphomas: clinical features and prognostic factors of 92 cases defined by the revised European American lymphoma classification.

The purpose of this study was to better define the clinical features and natural history of peripheral T-cell lymphomas (PTCL) entities included in the Revised European American lymphoma (REAL) classification. Cases of PTCL were retrieved from the records of the Department of Pathology and classified according to the REAL classification. In addition, cases of anaplastic large cell lymphoma (ALCL) were divided into classical, small cell, and primary cutaneous subtypes, and immunostaining for the anaplastic large-cell kinase (ALK) protein was performed on all cases of ALCL. Clinical features, response to therapy and survival were abstracted. Ninety-two cases of PTCL with adequate clinical information were retrieved. There were 40 cases of ALCL (30 classical, 7 small cell variant, 3 primary cutaneous), 28 PTCL, unspecified, 13 angioimmunoblastic T-cell lymphoma and 11 with other entities. The patients had a median age of 48 years with a range of 6-84 and had an estimated overall survival (OS) of 49% and progression-free survival (PFS) of 22% at 5 years. The International Prognostic Index (IPI) was a significant prognostic factor for both progression-free and OS. Histology was a significant predictor of PFS with anaplastic large cell having the best prognosis. ALK expression was not associated with an improved progression-free or overall-survival in patients with systemic T-cell ALCL. In conclusion, the REAL classification describes distinct PTCL entities. The IPI is the most important predictor of progression-free and OS in patients with PTCL. ALK expression may not provide prognostic information for systemic ALCL.

Adolescent↗

PubMed1998

Loss of pS2 protein expression is an early event of intestinal-type gastric cancer.

To investigate the prevalence of pS2 expression in gastric cancer with respect to tumor histopathology, intestinal metaplasia and Helicobacter pylori (H. pylori) infection, pathologic specimens of 91 patients with gastric cancer were immunostained for pS2. Such immunoreactivity was correlated with the status of H. pylori infection, tumor staging, histology, subtyping, and associated intestinal metaplasia. Positive pS2 staining was seen throughout all non-neoplastic epithelia, and in all 9 patients with the complete type of intestinal metaplasia. In contrast, 21 of 45 incomplete type of intestinal metaplasia had negative pS2 staining (P < 0.001), and 54 out of 91 tumors (59.3%) showed loss of pS2 expression in the cancer tissues proper. There was no correlation of pS2 expression with age, gender, depth of invasion, duodenal involvement, lymph node metastasis, venous invasion or H. pylori infection. Negative pS2 staining was significantly higher in the intestinal (74.5%) and Borrmann type I, II, III (64.2%) tumors than the diffuse (43.2%, P < 0.005) and Borrmann type IV (20%, P < 0.05) tumors. Our results indicate that loss of pS2 expression may occur as an early event in the malignant transformation process of intestinal-type tumors.

Adult↗

PubMed1998

Endothelial nitric oxide synthase exon 7 polymorphism, ischemic cerebrovascular disease, and carotid atheroma.

BACKGROUND AND PURPOSE: The role of endothelial nitric oxide synthase (eNOS) in normal physiology suggests that it could be a potential candidate gene for stroke. Reduced eNOS activity could mediate an increased stroke risk through hypertension or independent of hypertension through abnormal vasomotor responses, promoting atherogenesis, or increased platelet adhesion and aggregation. Recently, a common polymorphism in exon 7 of the eNOS gene (894G-->T) has been reported to be a strong risk factor for coronary artery disease. We determined whether it was also a risk factor for transient ischemic attack (TIA) and ischemic stroke and for carotid atheroma. METHODS: We studied 361 consecutive white patients presenting with ischemic stroke or TIA to a neurological cerebrovascular disease service and 236 normal white controls. In all patients CT and/or MR head imaging and high-resolution carotid duplex ultrasound were performed. The presence of the polymorphism (N/n) was determined by polymerase chain reaction and restriction with the enzyme BanII. RESULTS: There was no difference in the frequency of the NN genotype between patients and controls (13.0% versus 15.3%; P=0.44) or in N allele frequency (39% versus 37%; P=0.57). There was no association with genotype when only patients with stroke (excluding those with TIA) or when only individuals aged < or =65 years were considered. In contrast, there was a highly significant independent association between cerebrovascular disease and hypertension (odds ratio, 2.87; 95% CI, 2.0 to 4.15; P<0.00001), smoking (odds ratio, 2.58; 95% CI, 1.80 to 3.70; P<0.00001), and diabetes (odds ratio, 2.68; 95% CI, 1.38 to 5.24; P=0.004). There was no relationship between the polymorphism and any particular stroke subtype: large-vessel disease, for NN, 15 of 105 (14.3%); lacunar disease, 10 of 75 (13.3%); cardioembolic and unknown, 18 of 151 (11.9%); and tandem pathology, 4 of 30 (13.3%) (P=0.68, chi2). There was no difference in the mean degree of carotid stenosis between the 3 genotypes: NN, 31.1% (SD, 27.1); Nn, 30.1% (29.0); and nn, 31.2% (26.3) (P=0.9). There was no association between the NN genotype or the N allele and hypertension. CONCLUSIONS: We failed to find a relationship between this exon 7 polymorphism and ischemic cerebrovascular disease. In particular, it was not associated with stroke and TIA secondary to large-vessel atherosclerosis or with the degree of carotid stenosis in patients with cerebrovascular disease. It is unlikely that this particular polymorphism or any closely linked polymorphism is a major risk factor in the majority of white patients with stroke.

Aged↗

PubMed2003

Irritability in pediatric mania and other childhood psychopathology.

Irritability is an important symptom in childhood psychopathology that has received relatively little research attention. Recent controversy concerning the diagnosis of mania in children has focused attention on how little is known about how to assess irritability in a systematic way, and about its diagnostic associations. For example, subtyping irritability according to course (chronic vs. episodic), precipitants, and family history may facilitate the identification of psychopathology and the study of pathophysiology. While normative and pathologic irritability can be differentiated reliably, the validity of the distinction is unclear. In addition, there is a need for scales designed to measure the severity of irritability in children with mood and anxiety disorders. In order to facilitate research, we propose a definition of irritability from the perspective of affective neuroscience. Because reactive aggression may be a helpful animal model for irritability, we review the neural circuitry mediating this behavior. Behavioral paradigms that evoke frustration, as well as those that assess the ability to inhibit a prepotent motor response, maintain attentional focus, execute response reversal, recognize angry faces, and regulate emotional responses, may be useful in the study of irritability. Examples of such paradigms are described, and the pharmacology of irritability is reviewed briefly.

Adolescent↗

PubMed2006

Restricted localization of claudin-16 at the tight junction in the thick ascending limb of Henle's loop together with claudins 3, 4, and 10 in bovine nephrons.

Claudin-16 is one of the tight junction protein claudins and has been shown to contribute to reabsorption of divalent cations in the human kidney. In cattle, total deficiency of claudin-16 causes severe renal tubular dysplasia without aberrant metabolic changes of divalent cations, suggesting that bovine claudin-16 has some roles in renal tubule formation and paracellular transport that are somewhat different from those expected from the pathology of human disease. As the first step to clarify these roles, we examined the expression and distribution of claudin-16 and several other major claudin subtypes, claudins 1-4 and 10, in bovine renal tubular segments by immunofluorescence microscopy. Claudin-16 was exclusively distributed to the tight junction in the tubular segment positive for Tamm-Horsfall glycoprotein, the thick ascending limb (TAL) of Henle's loop, and was found colocalized with claudins 3, 4, and 10. This study also demonstrates that bovine kidneys possess segment-specific expression patterns for claudins 2-4 and 10 that are different from those reported for mice. Particularly, distribution of claudin-4 in the TAL and distal convoluted tubules was characteristic of bovine nephrons as were differences in the expression patterns of claudins 2 and 3. These findings demonstrate that the total lack of claudin-16 in the TAL segment is the sole cause of renal tubular dysplasia in cattle and suggest that the tight junctions in distinct tubular segments including the TAL have barrier functions in paracellular permeability that are different among animal species.

Amino Acid Sequence↗

PubMed2001

[Muscarinic receptor subtype-3 expression in trabecular meshwork of normal human eye and primary open-angle glaucoma].

OBJECTIVE: To identify the muscarinic receptor subtype-3 (M3-receptor) expression in trabecular meshworks (TM) of normal human eyes and eyes with primary open-angle glaucoma (POAG) and discuss the pathological changes of TM in POAG. METHOD: TM specimens were taken from 5 normal persons and 10 patients with POAG at late stage. Then LSAB immunohistochemical technique was used to identify M3-receptors. The results were observed under microscope and compared with computer-image-analysis system. RESULTS: (1) The trabecular meshwork cells in all the 5 normal persons expressed M3-receptors. The positive cells mainly existed in the uveal part of TM, from Schwalbe's line to scleral spur. (2) In TM from eyes with POAG, the amount of both TM cells and M3-receptor positive cells were reduced obviously, even some specimens had no such positive expression. The positive cells were correspondingly decreased in number and scattered in distribution. CONCLUSION: The TM cells in normal human eyes express M3-receptors. The TM cells and M3-positive cells in eyes with late POAG are reduced in number and their distribution is irregular.

Adolescent↗