An eye for horticulture.
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Anti-Bacterial Agents↗
Biomedical subjects
M A Miller
Publications and source records attributed to M A Miller.
Long-lived protective immunity to Listeria is conferred by immunization with particulate or soluble listerial antigen preparations coadministered with IL-12.
The ability of IL-12 to promote the development of Th1-type immune responses, and thus promote cellular immunity, has been well documented. In a previous report, we showed that coadministration of IL-12 with heat-killed Listeria monocytogenes elicited intense antigen-specific T cell responses that conferred protective listerial immunity. Herein, we have extended those studies by demonstrating that multiple injections of heat-killed L. monocytogenes and IL-12 elicit memory responses that confer long-lived (> or = 3 months) protective immunity and that immunity can be transferred adoptively with cells from immunized mice injected into naive mice. These studies have also demonstrated that the powerful adjuvanticity of IL-12 is observed with soluble as well as particulate immunogens and is operative in mouse strains that have different MHC haplotypes. These findings suggest that IL-12 may be a useful adjuvant component of vaccines for a wide variety of pathogens in animal and human systems.
Adjuvants, Immunologic↗
Liver lobe torsion and liver abscess in a dog.
A 4-year-old Rhodesian Ridgeback had acute onset of vomiting, lethargy, and discolored urine. Physical examination revealed lethargy, pyrexia, weak femoral pulses, cardiac arrhythmia, distended abdomen, and signs of pain on abdominal palpation. Abdominal radiography and ultrasonography revealed a gas-containing lesion in the cranial portion of the abdomen. Preoperative care included administration of fluids, antibiotics, and antiarrhythmic medication. Exploratory laparotomy revealed hemobilia and a 360 degrees clockwise torsion of the papillary process of the caudate lobe of the liver. Clinical signs resolved completely after liver lobectomy, and the dog was alive 2 years after surgery. Torsion of a liver lobe is rare in dogs. Necrosis of the involved liver lobe can result in acute weakness, shock, and death. Hemodynamic stabilization, antibiotic treatment, and surgical intervention have been successful in treating this condition. Liver lobe torsion should be considered on the differential diagnoses list of acute abdominal pain.
Animals↗
Few cholinergic neurons in the rat basal forebrain coexpress galanin messenger RNA.
The concept that galanin (GAL) is cosecreted with acetylcholine (ACh) into the ventral hippocampus is a major component of the current model delineating GAL regulation of the cholinergic memory pathways in the rat. Although GAL-immunoreactivity coexists in 50-70% of cholinergic neurons in the basal forebrain (BF) of colchicine-treated rats, the actual coexistence of these neurotransmitters in the basal state may be lower, because colchicine treatment was recently shown to both induce GAL gene expression and inhibit choline acetyltransferase (ChAT) gene expression in this brain region. We have used single and double in situ hybridization histochemistry to examine the distribution and coexistence of GAL and ChAT mRNAs in the BF of male and female rats. Compared with other forebrain regions, few GAL mRNA-expressing neurons are present within the cholinergic fields of the BF. The greatest number of GAL mRNA-expressing cells in this region are located within the nucleus of the horizontal limb of the diagonal band; but, even in this region, they represent only a small percentage (<20%) of ChAT mRNA-expressing cells. Our results indicate that few cholinergic neurons in the rat BF coexpress GAL mRNA and suggest that, in the basal state, GAL is not widely cosecreted with ACh into hippocampal memory centers.
Acetylcholine↗
Alloantigen gene therapy for squamous cell carcinoma of the head and neck: results of a phase-1 trial.
OBJECTIVE: To determine the safety and efficacy of an immunogenic gene therapy using a drug designed to produce expression of a foreign class I major histocompatibility complex protein in patients with head and neck cancer. DESIGN: Phase 1 prospective clinical trial. SETTING: Academic medical setting. PATIENTS: Nine patients with advanced head and neck squamous cell carcinoma who had failed conventional therapy and did not express HLA-B7, a class I major histocompatibility complex protein. INTERVENTION: Patients were treated with Allovectin-7 (Vical Inc, San Diego, Calif) by direct intratumoral injection. Allovectin-7 contains a plasmid complementary DNA complexed with a cationic lipid, which results in expression of HLA-B7. MAIN OUTCOME MEASURES: Patients were assessed for any toxic effects and for any change in tumor volume. Biopsy specimens obtained before and after therapy were evaluated by immunohistochemistry to detect HLA-B7 expression and with the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay to detect any induction of apoptosis. RESULTS: There were no toxic effects of the gene therapy. In 4 of these 9 patients there was a partial response to treatment, evidenced by a gradual reduction in tumor size. One patient has remained alive for more than 17 months since commencing treatment, with no clinical evidence of disease but with persistent histological evidence of cancer. Analysis of the biopsy specimens from 2 of the patients who responded to therapy demonstrated HLA-B7 expression. The TUNEL assay demonstrated extensive apoptosis in both of these patients, suggesting that this may be the mechanism of tumor reduction. CONCLUSIONS: These data demonstrate the potential efficacy and lack of toxicity of this form of alloantigen gene therapy. A multi-institutional study has been initiated to expand on these findings.
Adult↗
Staurosporine-induced versus spontaneous squamous metaplasia in pre- and postmenopausal breast tissue.
Breast cancers from pre- vs. postmenopausal women display unique characteristics that may be related to differences in epithelial differentiation between these two populations. In addition to lobular development, lactational changes, and involution, breast epithelium can undergo metaplastic alterations, often in association with carcinoma. Because protein kinase C (PKC) regulates differentiation and proliferation in many cell types, we asked whether modulation of PKC activity could define biochemical differences in breast epithelium from pre- vs. postmenopausal women. Organ cultures of normal human breast were treated with PKC agonists and antagonists. Epithelial differentiation was evaluated based on morphologic criteria and the expression of cell-type specific proteins. Staurosporine, a nonspecific but extremely potent inhibitor of PKC, induced squamous metaplasia in eight of eight cases within 2 weeks of treatment. Other inhibitors of PKC, such as calphostin C and tamoxifen, had no effect on epithelial differentiation. Long-term treatment with phorbol esters also did not induce squamous metaplasia. However, stimulation of cAMP levels by forskolin and isobutyl-methyl-xanthene (IMX) rapidly induced squamous metaplasia, as has been previously reported. Surprisingly, squamous metaplasia occurred in 10 of 12 cultures derived from postmenopausal women in the absence of exogenous agents. Untreated cultures derived from premenopausal women never developed this type of epithelium (0 of 11). Therefore, breast epithelium from pre- and postmenopausal women responded differently to in vitro culture. Forskolin/IMX or staurosporine can reproduce these conditions, acting independent of menopausal status. Because staurosporine's action was unique among PKC inhibitors, staurosporine may induce squamous metaplasia of breast epithelium by a PKC-independent mechanism.
Adult↗
Inhibition of poly(ADP-ribose) polymerase rescues human T lymphocytes from methylmercury-induced apoptosis.
The objective of this investigation was to determine the role of poly(ADP-ribose) polymerase (PARP) in methylmercuric chloride (MeHgCl)-induced T-cell apoptosis. Following exposure of human T-cells to 2.5 microM MeHgCl, we observed PARP activation within 45 min. Maximal activation was observed at 90 min after MeHgCl treatment; thereafter, PARP activity declined. The loss in enzyme activity was coincidental with the cleavage of 116-kDa intact PARP protein to an 85-kDa fragment. To address the relationship between PARP activation and induction of apoptosis, we first examined the redox status of T cells treated with MeHgCl. We found that exposure of T cells to low concentrations of this toxicant resulted in decreased levels of reduced pyridine nucleotides and an increase in the relative amounts of oxidized flavoproteins. Thus, the possibility exists that activation of PARP leads to NAD+ depletion and thereby alters mitochondrial redox status. To determine if PARP activation is indeed part of the proapoptotic (destructive) response or a component of the antiapoptotic (protective) response, we employed two inhibitors: 3-aminobenzamide and nicotinamide. Pretreatment of T cells with these inhibitors protected cells from MeHgCl-induced apoptosis; this was seen as a reduction in the uptake of Hoechst 33258 and DNA fragmentation. Moreover, these inhibitors blocked MeHgCl-induced oxidative stress as evidenced by a reduction in reactive oxygen species (ROS) generation. These agents, however, failed to block MeHgCl-dependent decline in mitochondrial transmembrane potential (delta psi m). We conclude that PARP activation leads to proapoptotic events that contribute to MeHgCl-induced cell death.
Apoptosis↗
Mercuric chloride induces apoptosis in human T lymphocytes: evidence of mitochondrial dysfunction.
The major objective of our study was to define the mechanism by which mercuric chloride (HgCl2) induces human T-cell death. Human peripheral blood T-cells were exposed to 0-40 microm HgCl2 and then analyzed for biochemical and molecular features of T-cell apoptosis. HgCl2-treated cells exhibited increased Hoechst 33258 fluorescence while maintaining their ability to exclude the vital stain 7-aminoactinomycin D. To further evaluate cell death and distinguish between apoptosis and necrosis, translocation of phosphatidylserine to the outer layer of the plasma membrane (annexin V binding), DNA fragmentation (TUNEL assay), and cleavage of poly (ADP-ribose) polymerase (PARP) were assessed. In the presence of 20-40 microm HgCl2, T-cells exhibited increased annexin V binding (28%) and DNA fragmentation (31%). HgCl2-dependent PARP cleavage was also observed by Western blot analysis. Because degradative changes associated with apoptosis are often preceded by disruption of mitochondrial function, HgCl2-treated cells were assessed for disruption of the mitochondrial transmembrane potential (DeltaPsim) and development of the mitochondrial permeability transition state. Using DiOC6(3), we demonstrated that HgCl2 exposure resulted in a decrease in the DeltaPsim. Because a decline in DeltaPsim can disturb the intracellular pH (pHi), we used the fluorescent probe, SNARF-1, to assess intracellular acidification. Treatment of T-cells with HgCl2 resulted in reduced pHi from 7.0 to 6.7. Concomitant with these observations, the fluorescent probe, hydroethidine, was utilized to demonstrate that uncoupled mitochondrial electron transport resulted in increased reactive oxygen species (ROS) generation. Interestingly, in spite of these alterations to mitochondrial function, translocation of cytochrome c to the cytosol was not detected; this correlated with enhanced bcl-2 levels in HgCl2-treated cells. In conclusion, HgCl2 exposure results in oxidative stress and activation of death signaling pathways leading to apoptosis. Collectively, our studies indicate that individual mercurial species are capable of inducing T-cell death by activating specific apoptotic cascades.
Apoptosis↗
Patient-focused care and its implications for nutrition practice.
Patient-focused care is a central element in work redesign and restructuring of health-care delivery systems. It affects all levels of dietetics practice. Patient-focused care poses potential benefits and challenges for nutrition professionals, including opportunities to expand the scope of practice and to share traditional nutrition duties with others. This article provides a brief overview of the basic components and terms of patient-focused care and reviews a case study that illustrates how implementation of patient-focused care in a community hospital has influenced the hospital's organizational structure and delivery of nutrition care and services. A review of the initial goals of patient-focused care in relation to long-term outcomes provides perspective for those beginning or in the midst of the reengineering process.
Dietetics↗
Intestinal multinodular A lambda-amyloid deposition associated with extramedullary plasmacytoma in three dogs: clinicopathological and immunohistochemical studies.
Intestinal extramedullary plasmacytomas (EMPs) are rare tumours in dogs. Three cases of canine intestinal EMP with amyloid deposits are described in this report. These tumours, which were located in the rectal submucosa, had variable numbers of well-differentiated plasma cells and fewer multinucleated giant cells of plasmacytoid and histiocytic morphology, admixed with abundant amyloid. Two cases had metaplastic cartilage and bone within the amyloid deposits. Immunohistochemically, the plasma cells of all three tumours reacted for lambda-light chains of immunoglobulins but not for kappa-chains, indicating monoclonality. Plasma cells of two tumours were also positive to CD79a antiserum. Amyloid deposits were labelled with an A lambda (amyloid of immunoglobulin lambda-light chain origin) antiserum but not with antisera against its precursor protein, the immunoglobulin lambda-light chains, indicating possible conformational changes of amyloidogenic proteins during their transformation into amyloid.
Amyloid↗
Immunohistologic analysis of gastrointestinal and pulmonary carcinoid tumors.
Carcinoid tumors are potentially malignant neoplasms that arise in various body sites, including the lung and gastrointestinal tract. Those that appear cytologically atypical are more likely to behave aggressively than more typical carcinoid tumors. However, in the absence of cytological atypia or large tumor size, it is difficult to predict the biology of an individual tumor, because some lesions metastasize, whereas others do not. This study had four aims: (1) To study the expression pattern of p53, Ki-67, NCAM, and S-100 in carcinoid tumors and to relate these expression patterns to classical histopathologic features and to tumor location. (2) To identify nonhistological markers that might more accurately predict the early behavior of carcinoid tumors. (3) To determine whether sustentacular cells are present in carcinoid tumors arising in tissues derived from different embryological derivatives. (4) To determine the synaptophysin and chromogranin immunoreactivity in neuroendocrine tumors arising in various locations. The immunostaining reactions were quantitatively scored by three observers. Only 3 of the 39 tumors (all histologically atypical) were strongly positive for Ki-67; two of these were also strongly p53 immunoreactive. NCAM immunostaining differed according to the site of origin: 76.5% of foregut lesions, 58% of the midgut lesions, and 20% of hindgut lesions were positive. S-100 immunostaining ranged from 41% in foregut lesions to 50% in both the hindgut- and midgut-derived tumors. S-100-positive sustentacular cells were present in 20.5% of carcinoid tumors. All tumors stained with antibodies against synaptophysin. In contrast, 100% of midgut, 60% of hindgut, and 88% of foregut tumors were chromogranin positive. Carcinoid tumors tend to have low proliferative rates. p53 immunostaining tends to be strongly positive in tumors that are histologically atypical, but it is negative in typical carcinoid tumors arising in the gastrointestinal tract and lungs. Immunostaining reactions with antibodies to NCAM, S-100, and chromogranin differ depending on the site of origin. Synaptophysin stains 100% of carcinoid tumors regardless of their site of origin. In contrast, antibodies to chromogranin fail to stain 40% of hindgut tumors and 12% of foregut carcinoid tumors. S-100-positive sustentacular cells are present in foregut and midgut tumors but not in hindgut tumors.
Adult↗
Anatomy and function of extrahypothalamic vasopressin systems in the brain.
The most prominent sites of vasopressin (VP) production in the rat brain are the paraventricular nucleus, the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis (BST), and the medial amygdaloid nucleus (MA). Recently a number of new sites have been suggested, including the hippocampus, the diagonal band of Broca, and the choroid plexus. This chapter shows how differential regulation of these VP systems can be exploited to identify the contributions of individual VP systems to the various central functions in which VP has been implicated. It will focus on the development, anatomy, and function of the sexually dimorphic VP projections of the BST and MA. This system contains more cells and has denser projections in males than in females. This system is also extremely responsive to gonadal steroids as it only produces VP in the presence of gonadal steroids. It has been implicated in sexually dimorphic functions such as aggressive behavior as well as in non-sexually dimorphic functions such as social recognition memory. Using comparative studies done in prairie voles as an example, this chapter makes the case that the VP projections of the BST and MA may simultaneously generate sex differences in some brain functions and behaviors and prevent them in others.
Amygdala↗
A model to estimate the potential economic benefits of measles eradication for the United States.
Measles incidence is at a nadir in many parts of the world due to vaccination efforts. Although the technical feasibility of eradication has been acknowledged, financial and political commitment need to be concomitantly identified on the national and global level. We demonstrate the potential value of measles eradication by identifying the potential cost-savings to one country resulting from measles eradication. For the US, measles eradication would save $45 million annually. If achieved by the year 2010, the US would save $500 million to $4.1 billion depending on the year of elimination, post-eradication schedule and discount rate. Intensification of measles control efforts in the US beyond current levels would have minimal marginal benefits on disease burden reduction. Allocation of resources to achieve global measles eradication is the next level of efficiency which would provide substantial savings. Countries may adapt this model to estimate their savings for consideration of the required political and financial contribution towards a global measles eradication program.
Adolescent↗
Other food borne infections.
This article presents an update of several emerging or reemerging pathogens: Yersinia, Cryptosporidia, Cyclospora, Brucella, and Mycobacterium. All of these zoonotic pathogens show evidence of food borne transmission. Yersiniosis is presented as an emerging pathogen that has as its major route of transmission preparation and consumption of pork products. New evidence is presented that supports the transmission of brucellosis via the food chain, especially through contaminated raw milk and cheese. While TB has limited transmission via raw milk, it is highlighted as a reemerging infection due to the development of multiple drug resistance. Public health veterinarians stand in an excellent position to recognize these emerging diseases and apply intervention strategies to prevent and control these infections in the future. This article is intended to raise their consciousness as to the management and medical practices that can diminish food borne transmission.
Animals↗
Disparate effects of mild, moderate, and severe secondary hyperparathyroidism on cancellous and cortical bone in rats with chronic renal insufficiency.
The subtotally nephrectomized rat has often been used to investigate the etiology and treatment of secondary hyperparathyroidism (secondaryHPT), but it has been used less frequently to study the effects of secondaryHPT on bone. The recent development of a reliable and specific rat parathyroid hormone (PTH) immunoradiometric assay has provided an opportunity for a thorough investigation of the relationship between circulating, biologically active PTH, and the skeletal abnormalities that occur in chronic renal insufficiency (CRI). Rats were 5/6 nephrectomized (Nx) or sham operated and fed diets with varying levels of Ca and P for 12-14 weeks to induce differing magnitudes of secondaryHPT. Parathyroid gland volume increased by 80%-90% in 5/6 Nx rats in the mild and moderate secondaryHPT groups (2.3- and 7.7-fold higher PTH levels, respectively) and by 3.3-fold in the severe secondaryHPT group (12-fold increase in PTH). The increases in gland volume were caused primarily by cell hyperplasia. Mild secondaryHPT resulted in a 12% decrease in bone mineral density (BMD) across the entire femur, increased osteoclast numbers (N.Oc), unchanged osteoblast numbers (N.Ob), and decreased cancellous bone volume (Cn.BV) in the tibial metaphysis but, apart from increased marrow area, no major changes in cortical bone at the tibio-fibular junction. Moderate secondaryHPT was associated with no changes in femoral BMD, or in tibial Cn.BV, but N.Ob and bone formation rate (BFR) were markedly elevated. Increased periosteal, intracortical, and endocortical BFR and turnover were evident, and contributed to increased cortical porosity (Ct.Po). The changes were exaggerated in the severe secondaryHPT group; BMD was lower in the proximal, but higher in the distal femur, and Cn.BV, N.Ob, N.Oc, and BFR were increased by six-, seven-, three-, and 30-fold, respectively. Endocortical BFR was elevated 31-fold and the extensive Ct.Po (10%) decreased bone strength. However, Ct.Po was not apparent until PTH levels exceeded 500 pg/mL. Thus, in rats with CRI of similar magnitude, progressive secondaryHPT is associated with dramatically different effects on bone. Mild secondaryHPT caused loss of cancellous and endocortical bone, and moderate secondaryHPT tended to maintain both types of osseous tissue, whereas PTH levels >500 pg/mL resulted in substantial cortical bone loss, but cancellous bone gain.
Animals↗
Does severity of ischaemic coronary disease correlate with erectile function?
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Coronary Disease↗
Preliminary normative data on DSM-IV attention deficit hyperactivity disorder in college students.
Identification of attention deficit hyperactivity disorder (ADHD) in adults presents a number of problems because there is no one specific diagnostic test for the condition. Given this challenge, clinicians often struggle between restrictive and exclusionary diagnostic methods or overinclusive acceptance that ADHD is a prevalent and disabling problem. A modified version of the Attention Deficit Hyperactivity Rating Scale was administered to 468 students at a large midwestern university. Analysis of the results suggested that the degree of ADHD symptoms in college students is modest and indicated that cutoff scores of 4 for current symptoms of inattention and hyperactivity-impulsivity would be sufficient to identify a college student as distinct from the norm. Although it would be premature to accept the calculated thresholds completely, clinicians should be aware of these differences when evaluating college students for ADHD.
Adolescent↗
An assessment of the value of Haemophilus influenzae type b conjugate vaccine in Asia.
Haemophilus influenzae type b (Hib) is a leading cause of bacterial meningitis and pneumonia. Although invasive Hib disease has been reduced substantially wherever Hib conjugate vaccines have been introduced into routine childhood immunization schedules, these vaccines are more costly compared with the vaccines routinely used in the Expanded Program for Immunization. Consequently a model was constructed to compare the expected burden of Hib disease with and without a national vaccine program for various Asian countries. Cost of the vaccine program, expected benefits of reduced deaths and savings from prevented disease treatment were assessed for each country based on the model assumptions. Model outcomes were expressed as a net cost, cost per death prevented and cost per disability-adjusted life year for each country and economic stratum. With the assumption of a disease burden of meningitis and pneumonia comparable with that observed in other regions, the model predicts that 668000 cases of Hib pneumonia and 136000 cases of Hib meningitis would occur annually in this cohort resulting in 156000 deaths. Based on current vaccination coverage rates for the individual countries, the model predicted that approximately 136000 (87%) Hib deaths could be prevented annually with incorporation of Hib vaccine into the Expanded Program for Immunization. For each of the countries considered, routine vaccination with Hib would cost between 0.1 and 3.0% of per capita gross national product per child <5 years of age. Although Hib vaccine would be considered a cost-effective public health intervention, it may be cost-prohibitive to implement in the lowest income countries without initial donor assistance.
Asia↗