Biomedical subjects

D R Brown

Publications and source records attributed to D R Brown.

At least 127 records · Page 7Linked to original sources

PubMed1999

Accrual to breast cancer clinical trials at a university-affiliated hospital in metropolitan Detroit.

Despite the large number of available studies, most women with breast cancer do not participate in clinical trials, and this is especially true among lower income and minority women. In this study the authors surveyed the practice patterns of four medical oncologists who comprised the clinical breast service at a large urban university hospital to develop a better understanding of the clinical trials enrollment process for women with breast cancer. Of 136 new female breast cancer patients seen by the four physicians over a 7-month period, there were 47 women (34%) offered participation in a clinical trial, and 16 women (12%) were eventually enrolled. Women who were offered participation were more likely to be younger (p = 0.068) and to have earlier stage disease then were women not offered participation (p = 0.008). Women enrolled into a trial were also more likely to be younger, although this difference was not statistically significant (p = 0.114). Patient race was not associated with the accrual or enrollment process. Over half of the women were not offered participation in clinical trials because of the lack of available studies. Further work evaluating the process of patient enrollment and physician and patient barriers is necessary to develop effective strategies for recruitment into breast cancer clinical trials.

Breast Neoplasms↗

PubMed1999

Impact on process of trauma care delivery 1 year after the introduction of a trauma program in a provincial trauma center.

BACKGROUND: Trauma care delivery in Canada, even in major trauma centers, usually devolves to the most involved service. For patients with multisystem injuries, this is not always optimal and aspects of care outside the domain of the primary service are apt to be overlooked. Trauma care is necessarily multidisciplinary, and to be optimal, appropriate integration of the care process and prioritization are required. The purpose of this study was to examine the impact on care in a busy provincial trauma center, after the introduction of a trauma program with a clinical trauma service, revised trauma protocols, and a dedicated trauma unit. METHODS: Data were collected prospectively before and during the introduction of the program. Aspects of care studied included trauma patient volume, compliance with trauma team activation and trauma consultation protocols, delays to the operating room for hypotension or open fractures, delays in disposition to the unit, average length of stay, and mortality based on Trauma and Injury Severity Score analysis. Data are presented summarized by quarter, one before and four after the introduction of the program. Variance tracking was introduced before the last quarter. Differences between preprogram and postprogram performance were assessed by using analysis of variance (asterisks indicates p < 0.05 compared with preprogram performance). RESULTS: Trauma unit average length of stay decreased from 10.15 days initially to 9.66 and 9.14* days at 6 and 12 months, reducing costs. Improved survival was demonstrated by Trauma and Injury Severity Score methodology with z score achieving significance compared with Major Trauma Outcome Study outcomes after program implementation. CONCLUSION: Trauma care improvement can be achieved by a multidisciplinary team focusing on the process of care, developing a dedicated trauma service to manage the more seriously injured patients, collecting them onto a single unit, and initiating program management.

British Columbia↗

PubMed1999

Polarized helper-T-cell responses against Leishmania major in the absence of B cells.

B-cell-to-T-cell signaling can shape helper T (Th) cell responses. During infection with Leishmania major, Th response is critical in determining the outcome of disease. Resistance depends on the generation of a protective Th1 response, while susceptibility is mediated by the generation of a Th2 response. In this study, we determined whether B cells are required for the development of polarized Th1 and Th2 responses during infection with L. major. Mice lacking B cells due to disruption of the immunoglobulin M locus (microMT) were infected with L. major, and disease progression and Th cell development were assessed. On the genetically resistant C57BL background, both wild-type and microMT mice controlled the infection and mounted a Th1 response. On the genetically susceptible BALB/c background, both wild-type and microMT mice were susceptible to infection and generated Th2 responses. Thus, during L. major infection, neither direct antigen presentation or costimulation by B cells nor antibody-mediated effector functions are essential for the development of polarized Th responses.

Animals↗

PubMed1999

Detection of multiple human papillomavirus types in Condylomata acuminata lesions from otherwise healthy and immunosuppressed patients.

Condylomata acuminata, or genital warts, are proliferative lesions of genital epithelium caused by human papillomavirus (HPV) infection. HPV types 6 and 11 are most often detected in these lesions. Genital lesions consistent with exophytic condylomata acuminata were removed by excision biopsy from 65 patients, 41 of whom were otherwise healthy individuals (control group) and 24 of whom had conditions known to cause immunosuppression. Histologically, the majority of the lesions were typical condylomata acuminata. Three lesions removed from immunosuppressed individuals also contained foci of moderate to severe dysplasia (intraepithelial neoplasia grade II/III). A recently developed PCR and reverse blot strip assay was used to determine the specific HPV types present in the genital lesions. With a set of oligonucleotide primers based on the same primer binding regions used for the MY09 and MY11 primer pair, this PCR assay detects the presence of 27 HPV types known to infect the genital tract. All but two condylomata acuminata contained either HPV type 6 or 11. The predominant type in the lesions from control patients was HPV 6, while lesions from immunosuppressed types most often contained HPV 11. Condylomata acuminata from immunosuppressed patients contained significantly more overall HPV types than lesions from the control group. HPV types associated with an increased risk of dysplasia (high-risk types) were detected in 42 (64.6%) of the total of 65 specimens; 18 (43.9%) specimens were detected in the 41 otherwise healthy individuals, and 24 (100%) specimens were detected in the 24 immunosuppressed patients. HPV 16 was the most common high-risk type detected, found in 21 of 65 (32.3%) specimens. After HPV types 6 and 11, HPV types 53 and 54 were the most frequently detected low-risk HPV types. This study demonstrates that a high percentage of condylomata acuminata lesions contain multiple HPV types, including types associated with a high risk of dysplastic abnormalities. Further studies are needed to determine the influence these additional HPV types have on the epidemiology of genital tract HPV infections and the natural history of condylomata acuminata, especially in immunosuppressed patients.

Adolescent↗

PubMed1999

Limits in reliability of glycoprotein G-based type-specific serologic assays for herpes simplex virus types 1 and 2.

Type-specific serologic assays for herpes simplex virus (HSV) types 1 and 2 based on glycoprotein G-1 (gG-1) (HSV-1) and gG-2 (HSV-2) discriminate between antibodies against HSV-1 and HSV-2. We previously developed a Western blot assay using gG-1 and gG-2 expressed in baculovirus, performed extensive validation studies, and determined that it was both sensitive and specific for type-specific detection of HSV antibody. Here we report that, among a cohort of Thai military recruits, the serostatus of some individuals changed from positive to negative over time (6.6% among those ever positive for HSV-1, and 14.9% among those ever positive for HSV-2). We tested a subset of these specimens in three other gG-based assays: an enzyme-linked immunosorbent assay, an immunoblot strip assay, and a Western blot assay. Positive-to-negative shifts occurred in every assay; the frequency of the shifts ranged from 6. 1% to 21.2% of the specimen sets tested. There was only limited agreement among the assays concerning which individuals lost reactivity. This inaccuracy, exhibited by all of the assay protocols, was not predicted by validation studies employing specimens from cross-sectional studies and was most pronounced in HSV-2 testing. This argues for the inclusion of serial blood specimens in serologic assay validation procedures.

Adult↗

PubMed1999

Upper respiratory tract disease in the gopher tortoise is caused by Mycoplasma agassizii.

Upper respiratory tract disease (URTD) has been observed in a number of tortoise species, including the desert tortoise (Gopherus agassizii) and the gopher tortoise (Gopherus polyphemus). Clinical signs of URTD in gopher tortoises are similar to those in desert tortoises and include serous, mucoid, or purulent discharge from the nares, excessive tearing to purulent ocular discharge, conjunctivitis, and edema of the eyelids and ocular glands. The objectives of the present study were to determine if Mycoplasma agassizii was an etiologic agent of URTD in the gopher tortoise and to determine the clinical course of the experimental infection in a dose-response infection study. Tortoises were inoculated intranasally with 0.5 ml (0.25 ml/nostril) of either sterile SP4 broth (control group; n = 10) or 10(8) color-changing units (CCU) (total dose) of M. agassizii 723 (experimental infection group; n = 9). M. agassizii caused clinical signs compatible with those observed in tortoises with natural infections. Clinical signs of URTD were evident in seven of nine experimentally infected tortoises by 4 weeks postinfection (p.i.) and in eight of nine experimentally infected tortoises by 8 weeks p.i. In the dose-response experiments, tortoises were inoculated intranasally with a low (10(1) CCU; n = 6), medium (10(3) CCU; n = 6), or high (10(5) CCU; n = 5) dose of M. agassizii 723 or with sterile SP4 broth (n = 10). At all time points p.i. in both experiments, M. agassizii could be isolated from the nares of at least 50% of the tortoises. All of the experimentally infected tortoises seroconverted, and levels of antibody were statistically higher in infected animals than in control animals for all time points of >4 weeks p.i. (P < 0.0001). Control tortoises in both experiments did not show clinical signs, did not seroconvert, and did not have detectable M. agassizii by either culture or PCR at any point in the study. Histological lesions were compatible with those observed in tortoises with natural infections. The numbers of M. agassizii 723 did not influence the clinical expression of URTD or the antibody response, suggesting that the strain chosen for these studies was highly virulent. On the basis of the results of the transmission studies, we conclude that M. agassizii is an etiologic agent of URTD in the gopher tortoise.

Animals↗

PubMed1999

Effect of leptin deficiency on metabolic rate in ob/ob mice.

Reduced metabolic rate may contribute to weight gain in leptin-deficient (ob/ob) mice; however, available studies have been criticized for referencing O2 consumption (VO2) to estimated rather than true lean body mass. To evaluate whether leptin deficiency reduces energy expenditure, four separate experiments were performed: 1) NMR spectroscopy was used to measure fat and nonfat mass, permitting VO2 to be referenced to true nonfat mass; 2) dietary manipulation was used in an attempt to eliminate differences in body weight and composition between ob/ob and C57BL/6J mice; 3) short-term effects of exogenous leptin (0.3 mg. kg-1. day-1) on VO2 were examined; and 4) body weight and composition were compared in leptin-repleted and pair-fed ob/ob animals. ob/ob animals had greater mass, less lean body mass, and a 10% higher metabolic rate when VO2 was referenced to lean mass. Dietary manipulation achieved identical body weight in ob/ob and C57BL/6J animals; however, despite weight gain in C57BL/6J animals, percent fat mass remained higher in ob/ob animals (55 vs. 30%). Exogenous leptin increased VO2 in ob/ob but not control animals. Weight loss in leptin-repleted ob/ob mice was greater than in pair-fed animals (45 vs. 17%). We conclude, on the basis of the observed increase in VO2 and accelerated weight loss seen with leptin repletion, that leptin deficiency causes a reduction in metabolic rate in ob/ob mice. In contrast, these physiological studies suggest that comparison of VO2 in obese and lean animals does not produce useful information on the contribution of leptin to metabolism.

Animals↗

PubMed1999

Sympathetic control of BP and BP variability in borderline hypertensive rats on high- vs. low-salt diet.

This experiment tested the effect of a high-salt diet on the interaction between arterial blood pressure (BP) and sympathetic nerve activity (SNA) at rest and during a controlled behavioral stress at an early stage in the development of hypertension in borderline hypertensive rats (BHR). Ten rats were maintained on a high-salt diet (8% NaCl) while 14 were fed a low-salt diet (0.8% NaCl) for 8 wk. They were trained in a Pavlovian paradigm by following a conditional stimulus tone (CS+) with a 0.5-s shock. SNA and BP were measured by implanted electrodes around the left renal nerve and a catheter in the femoral artery, respectively. There were no detectable between-group differences in BP or in BP variability in the resting animal at the end of the 8-wk dietary treatment. Moreover, there were no significant between-group differences in the changes in SNA evoked by the CS+ tone. Conversely, the amplitude of the initial conditional increase in BP was significantly (P < 0.05) larger in the high-salt (6 +/- 0.6 mmHg; mean +/- SEM) compared with the low-salt (4 +/- 0.4 mmHg) group. In addition, the BP excursion (peak/trough) during CS+ was larger in the high (18.2 +/- 6.1 mmHg)- vs. low-salt (5.8 +/- 0.4 mmHg) diet-fed subjects. The ratio of the average percent change in mean BP to the average percent change in SNA at the beginning of CS+ was 0.029 +/- 0.004 for the low-salt group and 0.041 +/- 0.006 for the high-salt group. We find that, before the development of overt hypertension, the enhanced conditional BP response in the high-salt BHR appears to reside at the interface between changes in SNA and the effector response and not within the central nervous system. These observations help explain the increasing BP variability typically observed with the development of hypertension in humans.

Animals↗

PubMed1999

Low-frequency renal sympathetic nerve activity, arterial BP, stationary "1/f noise," and the baroreflex.

The object of this study is to quantify the very low frequency (i.e., <0.1 Hz) interactions between renal sympathetic nerve activity (SNA) and arterial blood pressure (ABP). Six rats were instrumented for chronic recordings of SNA and ABP. Data were collected 24 h after surgery at 10 kHz for 2-5 h and subsequently compressed to a 1-kHz signal. The power spectra and ordinary coherence were calculated from data epochs up to 1 h in length. The very low frequency spectra for both variables were fitted to a constant times f (-beta). The peak magnitude squared of the coherence near 0.4 Hz was 0.82 +/- 0.08, but the apparent linear coherence fell off quickly at lower frequencies so that it was close to zero for frequencies <0.1 Hz. Moreover, at these low frequencies beta, as computed by a coarse grain spectral analysis, was significantly (P < 0.01) different for SNA (0.66 +/- 0.12) and ABP (1.12 +/- 0.14). Assuming that SNA and ABP are stationary time series, the results of our classical spectral analysis would indicate that SNA and ABP are not linearly correlated at frequencies with a period more than approximately 10 s. Accordingly, we tested for stationarity by computing the spectral coherence and found that SNA and ABP are not stationary "1/f noise" within the frequency range from 0.02 to 2.0 Hz. Rather the SNA exerts control over the cardiovascular system through intermittent bursts of activity. Such intermittent behavior can be modeled by nonlinear dynamics.

Animals↗

PubMed1999

The hamster model of intraperitoneal Burkholderia mallei (glanders).

Thirty-one female Syrian hamsters (Mesocricetus auratus) were inoculated intraperitoneally with a lethal dose of Burkholderia mallei (Budapest strain). Hamsters were killed postinoculation on days 0 through 6. Lesions were first noted in the spleens on postinoculation day 1, and in mediastinal and mesenteric lymph nodes, mediastinum, liver, and bone marrow on day 2. Lesions were present in the lung and submandibular lymph nodes on day 3, and in the brain on day 5. The characteristic histopathologic change was necrotizing pyogranulomatous inflammation, often with hemorrhage. Lesions indicative of impaired vascular perfusion, such as ischemia and infarction, were evident at the later time points. Pathologic changes generally increased in severity and distribution with time, and almost all tissues were ultimately affected. Our findings suggest that intraperitoneal bacteria were rapidly transported to mediastinal lymph nodes by transdiaphragmatic lymphatics and ultimately seeded other tissues hematogenously. The results of the study indicate that the Syrian hamster is a useful small animal model for glanders.

Animals↗

PubMed1999

Persistence of maternal antibodies against Mycoplasma agassizii in desert tortoise hatchlings.

OBJECTIVE: To investigate Mycoplasma agassizii-specific maternal antibodies in desert tortoise (Gopherus agassizii) hatchlings. SAMPLE POPULATION: Plasma from 43 captive-reared desert tortoise hatchlings. PROCEDURE: ELISA for M agassizii-specific antibodies was performed. Four hatchlings from 4 clutches of 3 M agassizii-seropositive females with chronic upper respiratory tract disease (URTD) were tested on the day of hatching (set 1), and 20 hatchlings from 4 clutches of 4 M agassizii-seropositive females with URTD and 19 hatchlings from 4 M agassizii-seronegative healthy females were tested at 4, 8, 12, and 29 months old (set 2). Immunoblot analysis was performed to determine immunoglobulin classes in yolk and plasma of hatchlings. To determine infection status of hatchlings, yolk, egg shell membranes (set 1), and nasal lavage fluid (sets 1 and 2) were examined for M agassizii by use of polymerase chain reaction. RESULTS: Yolk and hatchling plasma had significantly lower amounts of specific antibodies than did plasma from adult females. The IgG and IgM antibodies were transferred, but M agassizii-specific antibodies were of the IgG class. Hatchlings were not infected with mycoplasmas. Offspring of sick females had significantly higher specific antibody titers than did offspring of healthy females. Titers were still significantly different in 1-year-old hatchlings. CONCLUSIONS: Desert tortoise females transfer specific IgG and IgM antibodies to their offspring that are still detectable after 1 year. CLINICAL RELEVANCE: Infection with M agassizii may be misdiagnosed in hatchlings with persistent maternal antibodies. Passively acquired antibodies may have a role in pathogenesis of mycoplasma-induced respiratory tract disease and other diseases.

Animals↗

PubMed1999

Adrenergic, cholinergic, and nonadrenergic-noncholinergic intrinsic innervation of the jejunum in horses.

OBJECTIVE: To determine the major neurotransmitters that regulate contractile activity in the jejunum of horses. SAMPLE POPULATION: Jejunal specimens from 65 horses without gastrointestinal tract lesions. PROCEDURE: Jejunal smooth muscle strips, oriented in the plane of the circular or longitudinal muscular layer, were suspended isometrically in muscle baths. Neurotransmitter release was induced by electrical field stimulation (EFS) delivered at 30 and 70 V intensities and at various frequencies on muscle strips maintained at low or high muscle tone. To detect residual nonadrenergic-noncholinergic neurotransmission, the response of muscle to EFS in the presence of adrenergic and cholinergic blockade was compared with the response in the presence of tetrodotoxin. RESULTS: Atropine (ATR) decreased the contractile response of muscle strips to EFS under most conditions. However, ATR increased the contractile response of high-tone circular muscle. Adrenergic blockade generally increased the muscle responses to 30 V EFS and in high-tone longitudinal muscle but decreased contractile responses in high-tone circular muscle. Tetrodotoxin significantly altered the responses to EFS, compared with adrenergic and cholinergic receptor blockade. CONCLUSIONS: Acetylcholine and norepinephrine appear to be important neurotransmitters regulating smooth muscle contractility in the equine jejunum. They induce contraction and relaxation, respectively, in most muscle preparations, although they may cause opposite effects under certain conditions. In addition, nonadrenergic-noncholinergic excitatory and inhibitory influences were detected. CLINICAL RELEVANCE: Acetylcholine or norepinephrine release within the myenteric plexus of horses may alter gastrointestinal motility.

Adrenergic Agents↗

PubMed1998

Prion protein-overexpressing cells show altered response to a neurotoxic prion protein peptide.

A peptide fragment of the prion protein, PrP106-126 is toxic to neuronal cells in culture. This toxicity is dependent on neuronal expression of the prion protein (PrPc) and also the presence of microglia. The role of expression of the PrPc in neurotoxicity of this peptide was investigated using mice that overexpress the prion protein. Cells derived from two different strains of PrPc-overexpressing mice were used (Tg20 and Tg35). PrP106-126 was more toxic to Tg35 cerebellar cells than wild-type or Tg20 cells. This increased toxicity required the presence of microglia. Analysis of microglia derived from wild-type and PrPc-overexpressing cells showed that Tg35 microglia were more easily activated than wild-type microglia, were more easily stimulated to proliferate by astrocytes, and had a higher level of PrPc expression. This may explain the increased PrP106-126 toxicity to Tg35 PrPc-overexpressing cerebellar cells. These results suggest that the toxicity of PrP106-126 may depend on the level of expression of PrPc by microglia as well as by neurones.

Animals↗

PubMed1998

The porcine mu opioid receptor: molecular cloning and mRNA distribution in lymphoid tissues.

The porcine mu opioid receptor (pMOR), was cloned from cerebral cortex RNA using PCR methodologies. Porcine MOR is 96% identical with human MOR in amino acid sequence. An RT-PCR survey for pMOR mRNA indicated that pMOR is widely distributed in the gut, and is present in thymus and Peyer's patches but absent in other immune tissues and in isolated immune cells. Based on these findings, it appears that opioids do not exert an immunosuppressive effect through direct interaction with the mu-opioid receptor on immune cells. In certain tissues, however, opioids may modulate immune function indirectly through neuronal MOR.

Animals↗

PubMed1998

A human papillomavirus related to human papillomavirus MM7/LVX82 produces distinct histological abnormalities in human foreskin implants grown as athymic mouse xenografts.

Studies of human papillomaviruses (HPVs) are hampered by the lack of a conventional culture system because HPV completes its life cycle only in fully differentiated human tissue. To overcome this obstacle, the athymic mouse xenograft system has been used to study the pathogenesis of HPV 11 and to develop neutralizing assays for vaccine development. Recently, HPV 40 has been produced in this system, and HPV 16 has been produced using mice with severe combined immune deficiency. To identify and characterize additional genital HPV types for similar studies, condylomata acuminata lesions containing a high copy number of HPV and detectable L1 major capsid protein were used to prepare infectious virus stocks. Human foreskin fragments were infected with the virus preparations and implanted under the renal capsules of athymic mice. After 5 months of growth, implant tissue was removed and processed for studies to detect HPV infection. Evidence of HPV infection was noted in some of the implants, but in contrast to HPV 11-infected epithelium, the implants derived from the new virus preparations contained a lesser degree of acanthosis, less developed koilocytosis, and a reduced number of preserved nuclei in the hyperkeratotic material within the cyst lining. The L1 consensus region was amplified by polymerase chain reaction from implant DNA and sequenced. Alignment of the amplified sequences with those in the HPV sequence database showed that the 452-bp amplimer was closely related but not identical to HPV LVX82 and HPV MM7 (also called Pap 291). The entire 7.9-kb genome was amplified by polymerase chain reaction and cloned. The presence of virions of the new isolate (named HPV IU) in the implants was verified by immunohistochemical detection of L1 major capsid protein and by demonstration of virion particles by electron microscopy. A second extract was made from one of the new implants and used to successfully propagate HPV IU. These experiments demonstrate that experimental infection of human epithelium with the new isolate, HPV IU, is associated with histological abnormalities that differ in potentially important ways from the changes observed in experimental HPV 11 infection.

Animals↗

PubMed1998

Prion protein expression and superoxide dismutase activity.

The function of the prion protein (PrPc) remains uncertain. It has been suggested that prion protein expression may aid cellular resistance to oxidative stress by influencing the activity of Cu/Zn superoxide dismutase (Cu,Zn SOD). The activity of Cu,Zn SOD was investigated in mice with different levels of PrPc expression. Increasing levels of PrPc expression were linked to increased levels of Cu,Zn SOD activity. Western-blot and Northern-blot analysis indicated that mice either lacking or overexpressing PrPc had levels of Cu,Zn SOD mRNA equivalent to those expressed in wild-type mice. Mice overexpressing the prion protein had lower levels of resistance to oxidative stress but higher expression levels of glutathione peroxidase, probably due to increased levels of hydrogen peroxide produced by increased Cu,Zn SOD activity. When cells were metabolically labelled with radioactive copper, increased radioactivity was immunoprecipitated with Cu,Zn SOD from mice with higher levels of PrPc. In addition, diethyldithiocarbamate, a copper chelator that inactivates Cu,Zn SOD by capturing copper from the molecule, is more able to inactivate Cu,Zn SOD expressed in animals with higher levels of PrPc. As recent studies have suggested that PrPc may regulate some aspect of copper metabolism, it is suggested that PrPc expression may regulate Cu,Zn SOD activity by influencing copper incorporation into the molecule.

Animals↗

PubMed1998

Microglial expression of the prion protein.

The prion protein (PrPc) is a normal cellular protein expressed by neurones and astrocytes. An altered isoform, PrPSc is thought to transmit spongiform encephalopathies. Here we show that microglia also express PrPc. Sensitivity of microglia to activation is enhanced by increased expression of PrPc. Bacterial endotoxin increases superoxide production and inhibits profileration of microglia more effectively when microglia express PrPc. PrPc expression is therefore important for the normal function of microglia.

Animals↗

PubMed1998

Prion protein fragment interacts with PrP-deficient cells.

A fragment of the prion protein (PrP106-126) induces cell death in cultures of wild-type embryonic day (E)16 mouse cortical neurons but not cells derived from mice devoid of cellular PrP(PrPo/o). Two common binding partners for PrP106-126 expressed in both wild-type and PrPo/o mouse brain were isolated and their sequences determined. The two proteins were found to be alpha and beta tubulin. Further evidence that tubulin binds PrP106-126 within cells comes from cell culture experiments. Colchicine toxicity on PrPo/o mouse cortical cells is enhanced by PrP106-126 and taxol enhances toxicity of PrP106-126 on wild-type mouse cortical cells. Our evidence shows that a fragment of PrP can bind a cellular protein and in so doing, alters the metabolism of cells even when they do not express native PrP. This indicates that PrP106-126 is nontoxic to PrPo/o cells, not because of an inability to interact with these cells but because of the loss of some aspect of a PrP expression-dependent phenotype.

Amino Acid Sequence↗