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R Day

Publications and source records attributed to R Day.

At least 127 records · Page 7Linked to original sources
PubMed1995

Base-line quality-of-life assessment in the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial.

BACKGROUND: The Breast Cancer Prevention Trial (BCPT) is a large, multicenter chemoprevention trial testing the efficacy of the antiestrogen drug tamoxifen for prevention of breast cancer and coronary heart disease in healthy women at high risk of breast cancer. The BCPT evolved from a series of prior studies in early stage breast cancer demonstrating the efficacy of tamoxifen in the prevention of systemic breast cancer recurrence and in the reduction of contralateral breast cancers. PURPOSE: The purpose of this article is to describe the methodologic considerations in the collection of health-related quality-of-life (HRQL) data in the BCPT and to present base-line HRQL data on the first 9749 participants. METHODS: An HRQL questionnaire that included the Center for Epidemiologic Studies-Depression Scale, a symptom checklist, the Medical Outcomes Study 36-item short form (MOS-SF-36), and the MOS sexual problems questions was completed by participants in the BCPT at base line (prior to random assignment). Medical and demographic information, as well as projected risk of breast cancer, were collected as part of study eligibility. Descriptive and correlational data were examined for these study participants. RESULTS: BCPT participants report high levels of functioning compared with U.S. general population norms but still report an average of 8.9 distinct symptoms during the past 4 weeks. Depression is less prevalent among the participants than in community samples, which reflects the exclusion of clinically depressed individuals. Sixty-five percent reported being sexually active in the past 6 months, with an age-related decline in sexual activity. Younger women reported fewer sexual problems than older women. There is a strong correlation between the two mental health measures, moderate to weak correlations between HRQL scales and levels of self-reported symptoms, and only weak correlations between measures of breast cancer risk and HRQL scales. The MOS-SF-36 scores were examined for three consecutive recruitment samples (0-6 months, 7-12 months, and 13-20 months), and the base-line scores were slightly better for the earliest group of participants. CONCLUSIONS: This article demonstrates the feasibility of collecting HRQL data in a large, multicenter, chemoprevention trial for women at high risk of breast cancer. The successful integration of HRQL data collection into this clinical trial attests to its value as a safety-monitoring end point and as an explicit and measurable outcome for the entire trial. IMPLICATIONS: HRQL data are important for studies in which healthy populations are involved and in which the potential for decrements in quality of life are real or perceived.

Adult↗
PubMed1995

Proparathyroid hormone is preferentially cleaved to parathyroid hormone by the prohormone convertase furin. A mass spectrometric study.

Parathyroid hormone (PTH), an 84-amino acid peptide, is the major regulator of blood calcium homeostasis. Its mRNA, in addition to encoding the mature peptide, also encodes a "pre" sequence of 25 amino acids and a basic "pro" hexapeptide. To assess which of the subtilisin-like prohormone convertases can process proPTH to PTH we coinfected cells with a vaccinia virus construct expressing human preproPTH and vaccinia virus constructs expressing furin, PC1 or PC2. BSC-40 cells, having a constitutive secretory pathway, and GH4C1 cells, having a regulated secretory pathway, were used. PTH biosynthetic products in cell extracts and media were purified by high performance liquid chromatography, identified by radioimmunoassay, and unambiguously defined as either proPTH or PTH by ion-spray mass spectrometry. In both cell types, furin was the most effective in processing proPTH to PTH. In all cases only PTH was released into the medium. In addition, partially purified furin and PC1 were tested for their ability to appropriately cleave a tridecapeptide spanning the prohormone cleavage site found in proPTH. Here too furin was much more effective at cleaving at the correct site. Northern blot analysis and in situ hybridization showed that furin and preproPTH mRNA are co-expressed in the parathyroid, whereas PC1, PC2, and PC5 are not and PACE4 is expressed only at very low levels. Taken together these studies strongly suggest that furin is the enzyme responsible for the physiological processing of proPTH to PTH.

Amino Acid Sequence↗
PubMed1995

Processing specificity and biosynthesis of the Drosophila melanogaster convertases dfurin1, dfurin1-CRR, dfurin1-X, and dfurin2.

Pro-protein and pro-hormone convertases are subtilisin/kexin-like enzymes implicated in the activation of numerous precursors by cleavage at sites mostly composed of pairs of basic amino acids. Six members of this family of enzymes have been identified in mammals and named furin (also called PACE), PC1 (also called PC3), PC2, PACE4, PC4, and PC5 (also called PC6). Multiple transcripts are produced for all the mammalian convertases, but only in the cases of PC4, PACE4, and PC5 does differential splicing result in the modification of the C-terminal sequence of these enzymes. A similar molecular diversity is also observed for the convertases of Hydra vulgaris, Caenorhabditis elegans, and Drosophila melanogaster. In the third species, two genes homologous to human furin called Dfur1 and Dfur2 have been identified. The Dfur1 gene undergoes differential splicing to generate three type I membrane-bound proteins called dfurin1, dfurin1-CRR, and dfurin1-X, which differ only in their C-terminal sequence. By using recombinant vaccinia viruses that express each of the dfurin proteins, we investigated the potential effect of the C-terminal domain on their catalytic specificities. For this purpose, these enzymes were coexpressed with the precursors pro-7B2, pro-opiomelanocortin, and pro-dynorphin in a number of cell lines, and the processed products obtained were characterized. Our studies demonstrate that these proteases display cleavage specificities similar to that of mammalian furin but not to that of PC2. In contrast, we noted significant differences in the biosynthetic fates of these convertases. All dfurins undergo rapid removal of their transmembrane domain within the endoplasmic reticulum, resulting in the release of several truncated soluble forms. However, in the media of cells containing secretory granules, such as GH4C1 and AtT-20, dfurin1-CRR and dfurin2 predominate over dfurin1, whereas dfurin1-X is never detected. While pro-segment removal occurs predominantly in the trans-Golgi network for all the dfurins, in the presence of brefeldin A, only dfurin1-CRR and dfurin2 can undergo partial zymogen cleavage. The conclusions drawn from the results of this study may well be applicable to the mammalian convertases PC4, PACE4, and PC5, which also display C-terminal sequence heterogeneity.

Amino Acid Sequence↗
PubMed1995

The distinct gene expression of the pro-hormone convertases in the rat heart suggests potential substrates.

The present study examined the distribution of the pro-hormone convertases PC1, PC2, furin, PACE4 and PC5 in the rat heart. Northern blot analysis of RNA extracted from cardiac tissues showed high levels of furin and PACE4 mRNA in the atria and ventricles, while PC5 mRNA was found to be expressed at high levels in the dorsal aorta. Although undetectable by Northern blot analysis, both PC1 and PC2 mRNA were detected by in situ hybridization and immunohistochemistry in discrete regions of the intracardiac para-aortic ganglia. In situ hybridization studies also showed that furin mRNA was observed in all cardiac tissues and cells, consistent with the previously reported ubiquitous expression of this gene. PACE4 mRNA was highly abundant in both the atria and ventricular cardiomyocytes, with low to undetectable levels observed in blood vessels. Finally, PC5 transcripts were expressed in the endothelial cells lining coronary vessels and the valve leaflets of the heart. The present localization studies in the heart and cardiac blood vessels suggests potential roles for each convertase in the processing of various neuropeptides, hormones and growth factors.

Amino Acid Sequence↗
PubMed1995

In situ hybridization shows increased endothelin-1 mRNA levels in endothelial cells of blood vessels of deoxycorticosterone acetate-salt hypertensive rats.

Endothelin-1 is a potent vasoconstrictor peptide produced in blood vessels and other tissues that may play an important role in the control of local blood flow and could be involved in the pathogenesis of hypertension. Our previous studies have documented increases in endothelin-1 peptide content and gene expression in mesenteric arteries and thoracic aorta of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Although changes in endothelin-1 were observed in the blood vessels of hypertensive rats, the exact cellular sites of these changes were not identified clearly. In the present study we investigated endothelin-1 gene expression in DOCA-salt hypertensive rats by in situ hybridization histochemistry using a high specific activity 35S-labeled complementary RNA probe. Robust increases in endothelin-1 mRNA levels were observed in both mesenteric blood vessels and aorta of DOCA-salt hypertensive rats as compared with the vessels from the uninephrectomized control rats. In both cases it was shown clearly that these increased endothelin-1 mRNA levels only originated in the endothelial cell layer, not in the underlying smooth muscle cells. Higher expression levels of endothelin-1 mRNA by the endothelial cells of DOCA-salt hypertensive rats may play an important role in vascular hypertrophy and in the maintenance of elevated blood pressure in this and perhaps other models of experimental hypertension.

Animals↗
PubMed1995

Increased endothelin-1 gene expression in the endothelium of coronary arteries and endocardium in the DOCA-salt hypertensive rat.

Endothelin-1 (ET-1) is a potent vasoconstrictor and inotropic agent which may also induce cell hypertrophy. The role of ET-1 in ventricular hypertrophy in hypertension is unknown. We investigated ET-1 gene expression and immunoreactive ET-1 (ir-ET-1) concentration in the heart of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. To identify the cellular sites of ET-1 production in the heart, we performed in situ hybridization histochemistry. DOCA-treated rats which underwent unilateral nephrectomy (Uni-Nx) or not, exhibited mild systolic blood pressure elevation and ventricular hypertrophy. Blood pressure elevation and cardiac hypertrophy were more severe in DOCA-salt hypertensive rats. Ventricular ET-1 mRNA was similar in Uni-Nx control and DOCA-treated rats by Northern blot analysis, whereas in DOCA-salt hypertensive rats it was significantly increased. Ir-ET-1 concentration was also enhanced in ventricles from DOCA-salt hypertensive rats compared with Uni-Nx control rats. In situ hybridization histochemistry using a 35S-labelled complementary RNA ET-1 probe demonstrated that the level of ET-1 mRNA transcripts was increased exclusively in endothelial cells of large epicardial and small intramyocardial coronary arteries and in areas of the endocardium, but not significantly in myocardial cells of either the atria or ventricles. Enhanced ET-1 production may contribute to vascular changes, both structural and functional, in the heart in this model of hypertension in the rat, but probably does not contribute to the severe cardiac hypertrophy found in DOCA-salt hypertensive rats.

Animals↗
PubMed1995

Prediction of thoracic and lumbar vertebral body compressive strength: correlations with bone mineral density and vertebral region.

The bone density of thoracolumbar vertebral columns (T1 to L5) from 18 individuals was measured using quantitative computed tomography and dual energy x-ray absorptiometry. Three hundred six isolated vertebral bodies were tested in a materials test device to determine their compressive strength. Between T1 and L5 the mean segmental increase in bone mineral content was 0.3 g, while the corresponding mean decrease in trabecular density was 4.7 HU. Midvertebral body cross-sectional area increased by an average of 46 mm2 per segment and the mean segmental increase in compressive strength was 0.17 kN. Compressive strength was significantly correlated with bone mineral density measured with dual energy x-ray absorptiometry (r = 0.86). Vertebral trabecular density samples measured with quantitative computed tomography were poorly correlated with compressive strength (r = 0.28); however, this was improved when the trabecular density was multiplied by the midvertebral body cross-sectional area (r = 0.83). This study provides information concerning the relationships between density and mechanical properties of all thoracic and lumbar vertebral bodies across a wide age range. While the load-bearing capacity of the vertebral bodies is largely dependent on their geometry and bone density, this relationship has been only extensively tested for the lumbar spine. This study extends these observations over the lumbar and thoracic regions to provide a comprehensive analysis of the strength characteristics of each vertebral body. This is particularly important given the paucity of data on the thoracic spine where age-related vertebral fractures predominate. These data provide a basis for the development of models to predict the potential for thoracolumbar fractures in the elderly vertebral column.

Absorptiometry, Photon↗
PubMed1995

Maintained PC1 and PC2 expression in the AtT-20 variant cell line 6T3 lacking regulated secretion and POMC: restored POMC expression and regulated secretion after cAMP treatment.

Two variant cell lines were recently established from parent AtT-20 cells. Whereas HYA.15.10.T.2 have a reduced level of secretory granules, HYA.15.6.T.3 are completely devoid of both the regulated pathway of secretion and of dense-core secretory granules. AtT-20 cells normally express the processing enzymes PC1, PC2, furin, carboxypeptidase E, and peptidylglycine alpha-amidating monooxygenase, as well as proopiomelanocortin, chromogranin B, and 7B2. We measured the expression of these mRNAs in both variant cell lines. Although some differences in mRNA level were noted, HYA.15.10.T.2 and HYA.15.6.T.3 cell lines maintained their expression of the processing enzymes and of 7B2. Furthermore, PC1 and PC2 were shown to be functionally active in the HYA.15.6.T.3 cells. In contrast, proopiomelanocortin and chromogranin B mRNA levels were no longer detectable in HYA.15.6.T.3 cells. Interestingly, stimulation of the HYA.15.6.T.3 cells with cAMP restored proopiomelanocortin mRNA, beta-endorphin immunoreactivity, and dense-core granules. Furthermore, at the ultrastructural level, beta-lipotropin immunoreactivity was detected in granules of cAMP-induced HYA.15.6.T.3 cells. Finally, depolarization of cAMP-induced HYA.15.6.T.3 cells with 56 mM potassium chloride resulted in a marked increase in the release of beta-endorphin immunoreactivity. These observations demonstrate that cAMP restores the regulated pathway of secretion in HYA.15.6.T.3 cells, which under untreated conditions do not demonstrate regulated release. These variant cell lines are unique models to understand better the relationship of the regulated pathway and the expression of the processing enzymes.

Animals↗
PubMed1995

An in vitro comparison of the susceptibilities of bacterial isolates from patients with conjunctivitis and blepharitis to newer and established topical antibiotics.

This retrospective study compared new and established topical antibiotics with regard to the in vitro susceptibility of bacterial isolates recovered from patients with conjunctivitis (n = 385) and blepharitis (n = 173) using the National Committee for Clinical Laboratory Standards-approved disk diffusion method. The percent susceptibility of recovered isolates to single antibiotic agents or combinations were ranked from greatest to least: chloramphenicol, bacitracin/polymyxin B, ofloxacin, sulfa, ciprofloxacin, trimethoprim/polymyxin B, norfloxacin, gentamicin, bacitracin, trimethoprim, tobramycin, neomycin, erythromycin, and polymyxin B. We determined that none of the available topical antibiotics provided 100% broad spectrum coverage in vitro. Established antibiotics often provided coverage comparable to the newer drugs. Due to the unproven value of in vitro testing as a predictor of clinical outcome in bacterial blepharitis and conjunctivitis, the ophthalmologist should choose therapy based on clinical experience, ongoing critical evaluation of available antibiotics, and cost-effectiveness.

Administration, Topical↗
PubMed1995

Prevalence of lens changes in Ukrainian children residing around Chernobyl.

The objective of this study is to determine the prevalence and characteristics of lens changes in the eyes of a pediatric population, 5-17 y old, living in the permanent control zone around the Chernobyl nuclear reactor and to compare these findings with those from an unexposed control population. A total of 1,787 children are reported on (996 exposed and 791 unexposed). Over three-quarters of the subjects examined in this study show a form of minor change, termed focal lens defect, in the cortical and/or nuclear portions of the lens of the eye. The exposed group shows a small (3.6%), but statistically significant excess (p = 0.0005) of subclinical posterior subcapsular lens changes similar in form to changes identified in atomic bomb survivors. These posterior subcapsular changes tend to occur in boys 12-17 y old and in exposed children who report consuming locally grown mushrooms on a regular basis.

Adolescent↗
PubMed1995

Cancers related to exposure to arsenic at a copper smelter.

OBJECTIVE: This is an update of an earlier study on the relation between exposure to arsenic in air and deaths from respiratory cancer. The purpose was to verify earlier findings of a supralinear dose response relation and to examine relations with other cancers, particularly those reported in studies on drinking water. METHODS: An earlier study of 2802 men who worked at a copper smelter for a year or more during the period 1940-64 and who were followed up for deaths during the period 1941-76 was updated until 1986. Estimates of exposure for the period 1977-1984 were added. RESULTS AND CONCLUSIONS: The additional follow up confirms the earlier finding that at low doses the increments in death rates for respiratory cancer for a given increment in dose are greater than at high doses. The additional follow up also shows significant increases in cancer of the large intestine and bone, and SMRs > 150 for cancer of the buccal cavity and pharynx, rectal cancer, and kidney cancer. There was a positive relation between exposure to arsenic in air and kidney and bone cancer, but none for the other cancers, except respiratory.

Air↗
PubMed1995

Expression of mRNA for somatostatin receptor (sstr) types 2 and 5 in individual rat pituitary cells. A double labeling in situ hybridization analysis.

To characterize cell specific expression of sstr subtypes in the pituitary we have analyzed mRNA for sstr1-5 in rat pituitary somatotrophs by reverse transcriptase polymerase chain reaction and determined the pattern and level of expression of mRNA for sstr subtypes 2 and 5 in individual pituitary cell subpopulations by double label in situ hybridization. Purified somatotrophs expressed mRNA for all 5 sstrs. In situ hybridization analysis revealed sstr5 mRNA in 70% of somatotrophs, 57% of thyrotrophs, 38% of corticotrophs, 33% of lactotrophs, and 21% of gonadotrophs. mRNA for sstr2 occurred in 40% of somatotrophs, 36% of thyrotrophs, 26% of lactotrophs, 3% of corticotrophs, and 8% of gonadotrophs. Not only were more cells positive for sstr5 mRNA but the average number of autoradiographic grains/cell was also higher for sstr5 than sstr2. These results show expression of multiple sstr genes in individual pituitary cells. mRNA for sstr2 and 5 occur in each of the 5 major pituitary cell subsets, sstr5 mRNA being more widely and more abundantly expressed than sstr2.

Animals↗
PubMed1995

Mouse insulinoma beta TC3 cells express prodynorphin messenger ribonucleic acid and derived peptides: a unique cellular model for the study of prodynorphin biosynthesis and processing.

The tumor cell line beta TC3 has been established from insulinomas derived from transgenic mice carrying a hybrid insulin promoter-simian virus-40 tumor antigen gene. The beta TC3 cells express high steady state levels of proinsulin messenger RNA (mRNA). In this same cell line, we describe in the present study high expression levels of prodynorphin (pro-Dyn) mRNA and its derived peptides. By Northern blot analysis, the screening of 23 cell lines of endocrine (n = 10) and of nonendocrine (n = 13) origin revealed the presence of high levels of the 2.6-kilobase pro-Dyn transcript only in beta TC3 cells. The beta TC3 cells expressed levels of pro-Dyn mRNA comparable to those in rat tissues expressing pro-Dyn. Chromatographic and radioimmunological studies showed that pro-Dyn mRNA was translated and fully processed into opioid peptides with leucine-enkephalin (Leu-Enk)-extended sequences [dynorphin-A-(1-8), dynorphin-B-(1-13), and alpha-neo-endorphin]. The expression of the prohormone convertases was also examined in beta TC3 cells by Northern blot analysis. In addition to the ubiquitously expressed furin, beta TC3 cells have abundant levels of prohormone convertase-1 (PC1) and PC2 mRNAs, but undetectable levels of PACE4 or PC5 mRNAs. Incubation of beta TC3 cells with 8-bromo-cAMP for 24 h stimulated 3-fold both the pro-Dyn mRNA levels and the secretion of opioid peptides. In contrast to pro-Dyn mRNA, furin, PC1, and PC2 mRNA levels were not affected by 8-bromo-cAMP. The beta TC3 cells constitute a unique model to elucidate the biosynthetic pathway of pro-Dyn processing, to identify the proteolytic enzymes responsible for the production of pro-Dyn end products, and to assess the potential role of opioid peptides in the regulation of pancreatic function.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Age-related alterations in the expression of prohormone convertase messenger ribonucleic acid (mRNA) levels in hypothalamic proopiomelanocortin mRNA neurons in the female C57BL/6J mouse.

POMC processing is mediated by the prohormone convertases (PC1 and PC2). The cleavage of beta-endorphin-(1-31) is mediated by PC2. PC2 can also further cleave beta-endorphin-(1-31) to beta-endorphin-(1-27). We previously reported a significant increase in the proportion of beta-endorphin-(1-27) and -(1-27) forms in the arcuate nucleus (ARC) of the hypothalamus in middle-aged females with irregular estrous cycles (5-7 days) compared to young female C57BL/6J mice with regular cycles (4-5 days). Changes in processing enzymes may be a mechanism underlying this change. We compared ARC messenger RNA (mRNA) levels of PC1, PC2, and furin by Northern blot and in situ hybridization analyses in young, middle-aged, and old mice. Antisense complementary RNA probes to mouse PC1, PC2, and furin were radiolabeled and used in single label studies, alone or in combination with a mouse POMC digoxigenin-labeled complementary RNA probe for double label studies. For Northern blot analysis, young (4- to 5-month-old) normally cycling (4-5 days) mice at diestrus were compared to middle-aged (12- to 13-month-old) irregularly cycling (5-7 days) mice at diestrus. By Northern blot analysis, a significant increase (P < 0.05) in ARC PC2 mRNA levels was detected in middle-aged compared to young mice, but ARC PC1 and furin mRNA levels were unaltered. Single label in situ hybridization analysis confirmed these findings in the general neuron population. We also observed a significant reduction in ARC furin mRNA levels in old mice compared to either young or middle-aged mice. Double labeling in situ hybridization histochemistry demonstrated that PC2 mRNA levels were significantly increased (at least 2-fold) in POMC mRNA-containing neurons of middle-aged compared to young mice. Selective changes in PC2 mRNA levels in ARC POMC neurons are correlated with changes in beta-endorphin-(1-31) processing to beta-endorphin-(1-27)/(1-26) in middle-aged animals. Our data suggest that the natural age-related shift in beta-endorphin peptide processing is mediated by PC2.

Aging↗
PubMed1995

HLA-DQ1 is associated with clinical response and survival of patients with melanoma who are treated with interleukin-2.

AIM: The risk of developing melanoma, the natural history of this disease, and the response to therapy with biological reagents may be determined, in part, by a patient's human leukocyte antigen (HLA) phenotype. In order to study this, the relationship between HLA type and clinical response to therapy with interleukin-2 (IL-2) was evaluated. METHODS: We retrospectively determined the HLA phenotype of 82 patients with metastatic melanoma who were treated with IL-2-based therapy. Fresh or frozen lymphocytes were serologically typed by standard lymphocytotoxicity techniques (NIH or Amos modified). The treatment regimens included IL-2 alone or with tumour infiltrating lymphocytes, lymphokine activated killer cells, cyclophosphamide, interferon-alpha, and tumour necrosis factor-alpha. Initially, the relationship between clinical response and each HLA antigen was evaluated by performing a two-tailed Fisher exact test. Associations with a P-value less than or equal to 0.10 without adjustment for multiple comparisons were considered worthy of further study. Independent confirmation of these apparent associations was obtained by studying the relationship between HLA phenotype and patient survival using Cox proportional hazards models. RESULTS: In the initial screening, a statistically significant association between clinical response and the expression of HLA-DQ1 was observed (unadjusted P2 = 0.0017). HLA-DQ1 was also independently associated with prolonged survival (P2 = 0.026). This positive association with survival was evident both for patients who responded to therapy and those who did not respond, as defined by > 50% tumour regression. CONCLUSIONS: Among patients with metastatic melanoma, HLA-DQ1 appears to be associated with clinical response to therapy using IL-2. This apparent association is confirmed by the observation that HLA-DQ1 is independently associated with prolonged survival in this group of patients.

Alleles↗
PubMed1995

Distinct mRNA expression of the highly homologous convertases PC5 and PACE4 in the rat brain and pituitary.

Posttranslational endoproteolysis is essential for the production of biologically active peptides from inactive precursors. Six kexin/substilisin-like endoproteases have been characterized in mammalian species. To understand the complex physiological functions of each convertase within a cellular context it is necessary to comprehensively define its tissue distribution and cohabitation with other members of the family. Previous studies demonstrated the distinct distribution of PC1, PC2, and furin mRNAs in the pituitary and brain, suggesting a unique function for each enzyme. In the present study, the mRNA tissue distributions of the two most recent and homologous members, PC5 and PACE4, were analyzed in rat pituitary and brain using in situ hybridization histochemistry. In the pituitary, the anterior lobe exhibited moderate levels of PC5 and high levels of PACE4 mRNAs. The intermediate lobe showed low levels of PC5 expression, while PACE4 mRNA levels were undetectable. PACE4 transcripts were detected throughout cells of the neural lobe suggesting expression in pituicytes. In the brain, PC5 expression was more restricted than PACE4. PC5 mRNA was detected only in neuronal cells, whereas PACE4 mRNA was expressed in both neuronal and glial cells. In areas that are rich in neuropeptides such as cortex, hippocampus, and hypothalamus, mRNA levels of PC5 were high but PACE4 were low or undetectable. In regions, such as the amygdaloid body and thalamus, distinct but complementary distributions of PC5 and PACE4 mRNAs were observed. The medial habenular and cerebellar Purkinje cells expressed very high levels of PACE4 mRNA. The present data strongly suggest unique tissue-specific functions of PC5 and PACE4.

Animals↗