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PubMed1977

Cytology of normal and inflamed conjunctivas in dogs and cats.

Conjunctival scrapings from normal dogs and cats were compared with conjunctival scrapings from dogs and cats with conjunctivitis. Normal scrapings usually contained sheets of epithelial cells and small numbers of bacteria. Goblet cells were not seen unless the scraping was made from the fornix. In the absence of other signs of ocular disease, an occasional leukocyte was considered normal. The changes in scrapings from inflamed conjunctivas included increased numbers of degenerating epithelial cells, fibrin, inflammatory cells, bacteria, and inclusion bodies.

Animals↗
PubMed2003

Aberrant intranuclear localization of biotin, biotin-binding enzymes, and beta-catenin in pregnancy-related endometrium and morule-associated neoplastic lesions.

Biotin-rich intranuclear inclusions, also known as optically clear nuclei, have been observed in various neoplastic and non-neoplastic lesions. They look like nuclei of herpesvirus-infected cells and cause a false-positive immunohistochemical result by avidin-biotin-complex (ABC) method. In the literature, all types of neoplastic lesions with intranuclear inclusions, with one exception, have been characteristically associated with squamoid structures known as morules. By contrast, all reported non-neoplastic lesions with such inclusions lacked morules and were confined to pregnancy-related endometrium. In the present study, adding unreported types of morule-associated neoplastic lesions, we investigated the distribution of biotin, biotin-binding enzymes, and beta-catenin in these lesions by immunohistochemical staining. We detected the intranuclear localization of biotin and of two mitochondrial biotin-binding enzymes (pyruvic acid carboxylase and propionyl CoA carboxylase) in all lesions examined, regardless of whether they were neoplastic or non-neoplastic and irrespective of the presence or absence of morules. The intranuclear localization of beta-catenin was detected in all neoplastic lesions with morules and in ovarian endometrioid adenocarcinoma without morules, but not in non-neoplastic endometrial lesions. These results suggest the following conclusions: (1) lesions with biotin-rich intranuclear inclusions can be classified as non-neoplastic/pregnancy-related endometrial and as neoplastic/pregnancy-unrelated or morular category; (2) the intranuclear biotin in both types of lesion is found in conjunction with biotin-binding enzymes. However, the role of beta-catenin in morule-associated neoplastic lesions, the relationship between beta-catenin and biotin/biotin-binding enzymes, and the mechanism of migration of biotin and biotin-binding enzymes from the cytoplasm to the nucleus remain unclear.

Biotin↗
PubMed2001

Nuclear magnetic imaging of an osmotic water uptake and delivery process.

The water absorption of NH4F-doped silicone cylinders was studied by spin-echo Fourier nuclear magnetic resonance imaging, in conjunction with gravimetric (mass uptake) and ionic concentration (release of NH4F) measurements. The addition of NH4F greatly increases the water uptake as the inclusions are surrounded by droplets of water when wetted by water diffusing in the polymer. These droplets then expand due to the osmotic pressure difference between the internal droplet and external solution; this expansion is opposed by an elastic restraining force. The rate of ingress into the polymer will depend on the relative chemical potential of water associated with the polymer and the droplet, as well as the diffusion coefficient. Later stages of the absorption process are dominated by the droplets. The dilution of the droplets (from water diffusing into the droplets) slowly reduces the chemical potential driving the process. Hence, the later stages occur without any notable concentration gradient but a slight chemical potential gradient. If the droplet expansion exceeds that which can be restrained by the material, failure around the droplet occurs resulting in the release of the salt and the solution within the droplet.

Ammonium Compounds↗
PubMed2003

Canine granulocytic ehrlichiosis (CGE) in Italy.

Medical records of thirty-five consecutive cases of canine granulocytic ehrlichiosis (CGE) diagnosed cytologically in Central Italy in 1995-2000 were analysed retrospectively. Tick exposure was reported in 16 dogs (45.7%) and concurrent babesiosis in 19 dogs (54.3%). Ehrlichia-like inclusion bodies were found in neutrophils in a percentage varying from 0.5% to 11%. Frequently recorded clinical signs included anorexia (71.4%), lethargy (45.7%), conjunctivitis (31.4%), fever (25.7%), lameness (20%) and ataxia (20%). Among the 16 representative dogs in which protein, electrophoresis was performed, 10 (62.5%) showed high globulin levels and 6 (37.5%) had concurrent high total protein levels. During treatment with doxycycline, all associated symptoms, including those unusually described, such as pyoderma intertrigo, erythema, apparent blindness and oral papillomatosis, progressively disappeared in 31 (89%) out of 35 dogs. The efficacy of treatment was marked in dogs simultaneously treated twice with imidocarb dipropionate: among the 14 dogs in which a fast recovery was noted, 11 (80%) were concurrently affected by babesiosis and consequently treated with the specific medicament leading to excellent outcomes. The main conclusion is that CGE is present among dogs from Central Italy and should be included in the differential diagnosis of possible zoonotic agents affecting the canine population.

Animals↗
PubMed1992

Ocular side effects of selected systemic drugs.

Numerous systemic drugs produce adverse effects that involve the eye. Pigmentary inclusions of the lids or conjunctivae or both may be caused by a variety of drugs, including amiodarone, chlorpromazine, and gold salts, while conjunctivitis and blepharoconjunctivitis have been associated with isotretinoin, sulfonamides, salicylates, and antineoplastic agents. Dry eye complaints may be caused by antihistamines, beta-receptor blocking agents prescribed for cardiovascular problems, antianxiety agents, and tricyclic antidepressants. Several drugs have been well documented as causes of keratopathies and/or lenticular deposits, including chloroquine and hydroxychloroquine, chlorpromazine, gold salts, systemic corticosteroids, nonsteroidal antiinflammatory drugs, and the antiarrhythmic agent amiodarone. Visual acuity may be decreased by transient changes in refractive error caused by sulfonamides, the antifungal agent metronidazole, thiazide diuretics, and carbonic anhydrase inhibitors. Dilation of the pupil may be caused by anticholinergic drugs, antihistamines, antidepressant agents, and central nervous system stimulants such as cocaine, methylphenidate, and amphetamines. Nystagmus, diplopia, and extraocular muscle palsies have been associated with central nervous system depressants, antihistamines, barbiturates, and elevated blood ethanol concentrations. Intraocular pressure can be elevated in susceptible individuals by long-term use of topical or systemic corticosteroids. Numerous drugs have been associated with retinal toxicity, including chloroquine and hydroxychloroquine, thioridazine, tamoxifen, and talc, which may embolize to the retinal circulation when administered by long-term drug abusers. The antituberculosis agents ethambutol and isoniazid have been implicated as causes of reduced acuity, visual field defects, and disturbances of color vision. Optic neuritis and retrobulbar neuritis may result from the use of chloramphenicol. This paper describes these and other adverse ocular effects that may be encountered when examining patients who are taking systemic drugs.

Amiodarone↗
PubMed1982

Effects of liposome structure and lipid composition on the activation of the tumoricidal properties of macrophages by liposomes containing muramyl dipeptide.

Various vesicle structures and lipid compositions have been studied to identify the optimal type of liposome for delivery of the macrophage-activating agent muramyl dipeptide (MDP) to macrophages. Evaluation of the ability of liposomes to be phagocytosed by macrophages established that optimal initial rates of engulfment were obtained when multilamellar vesicles (MLV) composed of distearoylphosphatidylcholine (18:0 PC): phosphatidylserine (PS) (7:3 mol ratio) were used. MLV composed exclusively of 18:0 PC were phagocytosed at rates greater than or equal to those of MLV composed of egg phosphatidylcholine (PC):PS, whereas MLV composed only of egg PC were very poorly phagocytosed. Although phagocytosis was enhanced by incorporation of PS into MLV, the inclusion of PS brought about significant enhancement in liposome permeability in the presence of serum. The inclusion of PS, however, was a requirement for the delivery of MLV to the lungs following i.v. injection into mice whether used in conjunction with 18:0 PC or egg PC. Activation of macrophages to become tumoricidal against syngeneic tumor cells wtih liposome-encapsulated MDP was superior in both degree and duration when MLV composed of 18:0 PC:PS (7:3 mol ratio) were used. MLV were found to be superior to large unilamellar vesicles containing equal amounts of lipid and entrapped MDP. On the other hand, higher levels of macrophage activation were obtained when an equivalent amount of a lipophilic MDP derivative, muramyltripeptide:phosphatidylethanolamine, was incorporated into the liposome bilayer irrespective of whether the adjuvant was incorporated in liposomes composed of 18:0 PC:PS or egg PC:PS.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMedDate not supplied

Nuclear grooves in cytologic preparations. A study of the utility of this feature in the diagnosis of papillary carcinoma.

The sensitivity and specificity of nuclear grooves and inclusions for papillary carcinoma was investigated in 32 touch preparations and 69 fine needle aspiration cytologic preparations of the thyroid. Ultrastructurally, these grooves and inclusions are cytoplasmic invaginations into the nucleus. Overall, 100% of the papillary carcinomas contained nuclear grooves while only 70% contained inclusions. Grooves, however, could be seen in 70% of nonpapillary neoplasms and in 56% of nonneoplastic conditions of the thyroid, albeit generally fewer in number and often not as distinct. Inclusions were present in 13% of nonpapillary neoplasms and were absent in nonneoplastic conditions. Some nuclei on cytologic preparations contain lines that are probably artifacts of chromatin alignment and do not represent true nuclear grooves. Since such lines may be indistinguishable from true grooves, grooves should be used cautiously and in conjunction with other criteria in the diagnosis of papillary carcinoma.

Carcinoma, Papillary↗
PubMed2006

Osteoarthritis: an example of phenoptosis through autonomic dysfunction?

Phenoptosis, the programmed death of organisms akin to cellular apoptosis, constitutes a type of Darwinian selection that enhances inclusive fitness. It provides a means by which senescent and pre-senescent members can self-terminate if they have incurred sufficient cumulative stress such that their continued survival detracts from inclusive fitness. Sepsis, vascular disease, menopause, cancer, and aging all represent examples of phenoptosis at work. We previously proposed that feed-forward autonomic dysfunction fundamentally drives phenoptosis in all its guises. Accordingly, we now postulate that osteoarthritis defines a type of biomechanical phenoptosis, mediated by feed-forward autonomic dysfunction, and manifested through joint destruction associated with fitness disadvantages. Biomechanical capability plays a significant role in evolutionary fitness, and sustained joint insults such as immobility or undue biomechanical stress may serve as proxies for inferior fitness. By both hindering an individual's ability to compete for energy and increasing that individual's vulnerability to predation, feed-forward joint destruction may facilitate adaptive phenoptosis among impaired or senile members. Empirical data suggests that contrary to common belief, heavy joint use does not necessarily cause osteoarthritis, whereas immobility and neuropathy can predispose to the condition. From a Darwinian perspective, another process mediated by sympathetic activity, the alarm cry of attacked prey, simultaneously promotes the escape of kin while attracting predators and scavengers. By effectively enabling the martyrdom of biomechanically-challenged individuals, osteoarthritis may serve to optimize system energy efficiency in a similar fashion. This framework may generalize to other situations where regenerative capacity dissipates in conjunction with maturation, typically leading to fibrosis. By allowing environmental pressure to sort the phenotypes, imperfect repair mechanisms may accelerate adaptation and optimize long-term inclusive fitness for all individuals. As the basis of competition shifts from biomechanical to cognitive skills, and as novel triggers for physical stress emerge, osteoarthritis may now represent a modern maladaptation.

Apoptosis↗
PubMed2004

Modified single-stranded oligonucleotides inhibit aggregate formation and toxicity induced by expanded polyglutamine.

Huntington's disease (HD) is caused by an increase in the length of the poly(Q) tract in the huntingtin (Htt) protein, which changes its solubility and induces aggregation. Aggregation occurs in two general phases, nucleation and elongation, and agents designed to block either phase are being considered as potential therapeutics. We demonstrate that inclusion formation can be retarded by introducing modified, single-stranded oligonucleotides into a model neuronal cell line. This cell-based assay is used in conjunction with a standardized biochemical assay to identify molecules that can disrupt the process of aggregate formation. Active oligonucleotides include a 6-mer containing a single phosphorothioate linkage on each terminus, a 53-mer and a 9-mer containing three phosphorothioate linkages at each end, and a 25-mer consisting of all modified RNA residues. The disruption process directed by the active oligonucleotides appears to be independent of sequence specificity and complementarity. In contrast, the activity is more dependent on the type of chemical modifications contained within the oligonucleotide. Some oligonucleotides that demonstrated inhibition activity were also found to extend the life span of PC12 cells after the toxic Htt aggregation process was induced. Our data provide the first evidence that short synthetic oligonucleotides inhibit a fundamental pathological pathway of HD and may provide the basis for a novel therapeutic approach.

Animals↗
PubMed2002

Effect of orlistat-induced weight loss on blood pressure and heart rate in obese patients with hypertension.

OBJECTIVE: To investigate the effects of long-term weight management with orlistat on blood pressure in obese hypertensive patients. DESIGN: A meta-analysis of data from five multicenter, randomized, placebo-controlled studies, conducted in Europe and the USA, was performed. PATIENTS: Obese adults [body mass index (BMI) 28-43 kg/m(2) ] with uncontrolled diastolic hypertension or isolated systolic hypertension (ISH) were eligible for inclusion. INTERVENTIONS: Following a 4-week placebo lead-in period, patients were randomized to orlistat 120 mg or placebo three times daily, in conjunction with a mildly reduced calorie diet for 1 year. MAIN OUTCOME MEASURES: Change in body weight was the primary efficacy parameter. Blood pressure, heart rate and systolic workload were assessed as secondary efficacy parameters. RESULTS: A total of 628 patients were included in the intent-to-treat (ITT) analysis. After 56 weeks, orlistat-treated patients had lost significantly more body weight than placebo recipients (8.0 versus 4.0%; P<0.001). Among patients with ISH, mean systolic pressure was reduced to a significantly greater degree after 1 year with orlistat compared to placebo (-9.4 versus -4.6 mmHg; P= 0.022). Similarly, reductions in mean diastolic pressure in patients with diastolic hypertension were greater with orlistat than with placebo (-7.7 versus -5.6 mmHg; P= 0.017). Weight loss of >or= 10% was associated with significant reductions in blood pressure, heart rate and systolic workload. CONCLUSIONS: Orlistat promotes clinically meaningful weight loss that is associated with significant reductions in blood pressure and heart rate, and may therefore have a role in the management of hypertension in overweight and obese patients.

Anti-Obesity Agents↗
PubMed1977

Mechanisms of the H-2 effect on viral leukemogenesis.

Evidence has been gathered which supports the notion that two distinct but interacting mechanisms, controlled by loci mapping within the H-2 complex, influence Friend murine leukemia virus (FV) disease. One mechanism, controlled by a gene mapping in or close to H-2D, influences the capacity of the H-2D gene product to form molecular complexes with FV molecules in the plasma membrane of infected cells. Formation of a complex appears to provide a target antigen for syngeneic cytotoxic T-lymphocytes, to cause co-capping of FV and H-2D antigens, to permit the selective inclusion of H-2Db molecules into progeny Friend virions, to influence the long-term maintenance of virus production in vitro and, in conjunction with the second mechanism, to stimulate the generation of cytotoxic T-lymphocytes. This second mechanism is controlled by a gene in the H-2K or H-2I region, and, in the presence of an H-2/FV molecular complex immunogen, influences the generation of H-2 restricted cytotxic T-lymphocytes and the rate of rejection of syngeneic FV-induced tumor cells.

Animals↗
PubMed1989

Evaluation of two multichannel tactile aids for the hearing impaired.

Two multichannel tactile devices for the hearing impaired were compared in speech perception tasks of varying levels of complexity. Both devices implemented the "vocoder" principle in their stimulus processing: One device had a 16-element linear vibratory array worn on the forearm and displayed activity in 16 overlapping frequency channels; the other device delivered tactile stimulation to a linear array of 16 electrodes worn on the abdomen. Subjects were tested in several phoneme discrimination tasks, ranging from discrimination of pairs of words differing in only one phoneme under tactile aid alone conditions to identification of stimuli in a larger set under tactile aid alone, lipreading alone, and lipreading plus tactile aid conditions. Results showed both devices to be better transmitters of manner and voicing features of articulation than of place features, when tested in single-item tasks. No systematic differences in performance with the two devices were observed. However, in a connected discourse tracking task, the vibrotactile vocoder in conjunction with lipreading yielded much greater improvements over lipreading alone than did the electrotactile vocoder. One possible explanation for this difference in performance, the inclusion of a noise suppression circuit in the electrotactile aid, was evaluated, but did not appear to account for the differences observed. Results are discussed in terms of additional differences between the two devices that may influence performance.

Adolescent↗
PubMed1993

Phocine distemper in a harp seal (Phoca groenlandica) from the Gulf of St. Lawrence, Canada.

The first case of phocine distemper in a seal from Canadian waters and the first case of clinical phocine distemper in a harp seal, Phoca groenlandica, is reported. A two-month-old female harp seal stranded on Prince Edward Island in May 1991. Significant clinical findings were lethargy and severe conjunctivitis. Pulmonary congestion was the main necropsy finding, and histological lesions included diffuse demyelinating nonsuppurative encephalitis and mild multifocal interstitial pneumonia. Acidophilic intracytoplasmic and intranuclear inclusions were present in cerebral neurons and astrocytes. Immunoperoxidase staining confirmed phocine distemper virus (PDV) antigen in the cytoplasm and nuclei of neurons, bronchiolar gland epithelium and transitional epithelium of the bladder. Infectivity titers of canine distemper virus (CDV) (Onderstpoort strain) and a morbillivirus isolated from a grey seal were significantly reduced by serum from the harp seal.

Animals↗
PubMed2004

Immunohistochemical and in situ detection of cytomegalovirus in lung autopsies of children immunocompromised by secondary interstitial pneumonia.

Secondary interstitial pneumonia (SIP), a disease affecting patients immunocompromised by primary underlying diseases during their treatment in hospital, is frequently associated with cytomegalovirus (CMV) infection, a potentially treatable condition. However, in many cases, no infectious agent can be determined, and this clinical disease rapidly progresses to death. Theoretically, SIP could be caused by CMV, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect the virus. To test the hypothesis that immunohistochemistry (IH) and in situ detection by hybridization (ISH) provides more accurate results than the mere histological demonstration of CMV inclusions, these methods were applied to 37 autopsied lung sections obtained from children immunocompromised by primary underlying diseases and who died of SIP. As a result, the cases were subdivided into three groups: (1) children with SIP CMV inclusions (Diffuse alveolar damage-DAD-related) (n = 7); (2) children with SIP without classical viral inclusions (CMV-DAD-related) (n = 3); (3) children with SIP exhibiting nuclear cytopathic effect (not CMV-NSIP-related) (n = 27). In the first group, all three techniques yielded clearly positive results, whereas IH and ISH indicated that three of the children of the second group had CMV-related DAD without histological demonstration of CMV inclusions. In the third group, there were no positive CMV signals. These data indicate that DAD-related CMV infection is an important cause of SIP and of death in children immunosuppressed by primary underlying diseases, and that IH and in situ detection were more sensitive than the histological demonstration of CMV inclusions. A direct involvement of CMV in SIP exhibiting DAD is likely, but not in the non-specific interstitial pneumonia (NSIP) pattern. We conclude that all children with primary underlying diseases should be investigated for CMV SIP using sensitive IH and in situ tests in conjunction with histological routine procedures.

Autopsy↗
PubMed2001

Molecular analysis of the Pi*Z allele in patients with liver disease.

Alpha1-antitrypsin (AAT) is the main protease inhibitor in human plasma. There are more than 75 variants of this protein that differ from each other by their isoelectric point. Most of these alleles cause a reduction in AAT levels; the most common allele is Pi*Z. The main complications related to the Pi*Z allele are obstructive pulmonary disease and liver disease. Some Pi*Z allele carriers present cholestatic jaundice and cirrhosis. The Z type is associated with a secretion defect, which leads to deficiency of AAT and to the formation of intrahepatocytic inclusions in affected subjects. The diagnosis of AAT deficiency can be made by different techniques, including molecular analysis, although the final diagnosis should be done in conjunction with demonstration of the periodic acid-Schiff-positive globules on liver biopsy. In this study, specimens of 29 patients with cryptogenic cirrhosis between age 1 month and 18 years, and of 100 controls were submitted to polymerase chain reaction followed by digestion with TaqI enzyme. Five of the 29 patients had undergone liver transplantation. Three patients were heterozygous for the Pi*Z allele, and two were homozygous (allele frequency = 12.07%; 7/58). Among the controls, who represented the population of Porto Alegre, 1 in 100 individuals was heterozygous for the Pi*Z allele, resulting in an allele frequency of 0.5% (1/200). The high frequency of Pi*Z alleles among the patients indicates the usefulness of AAT molecular testing in children with cholestatic jaundice and cirrhosis.

Adolescent↗
PubMedDate not supplied

The utility of traditional prehospital interventions in maintaining thermostasis.

OBJECTIVE: Hypothermia can have a negative effect on the metabolic and hemostatic functions of patients with traumatic injuries. Multiple methods of rewarming are currently used in the prehospital arena, but little objective evidence for their effectiveness in this setting exists. The purpose of this study was to assess the relative effectiveness of traditional prehospital measures in maintaining thermostasis in trauma patients. METHODS: Participating helicopter and ground ambulance ALS units were prospectively randomized to provide either routine care only (passive or no warming) or routine care (passive warming) in conjunction with active warming (either reflective blankets, hot pack rewarming, or warmed IV fluids). A total of 174 trauma code patients, aged >14 years, who met inclusion criteria were prospectively enrolled by prehospital providers. Patients who received a non-assigned intervention or who had incomplete temperature data were dropped from the analysis. A total of 134 patients were included in the final analysis. RESULTS: Patients who received hot pack rewarming showed a mean increase in body temperature during transport (+1.36 degrees F/0.74 degrees C), while all other groups (no intervention, passive rewarming, reflective blankets, warmed IV fluids, warmed IV fluid plus reflective blanket) showed a mean decrease in temperature during transport [-0.34 to -0.61 degrees F (-0.2 to -0.4 degrees C); p<0.01]. In addition, the hot pack group was consistent, with every patient who received hot pack warming showing an increase in body temperature during transport, while in all other groups there were patients who had both increases and decreases in temperature. The intervention groups did not differ significantly on exposure to precipitation, transport unit temperature, total prehospital time, initial vital signs, amount of fluid administered, Injury Severity Score, or Glasgow Coma Score. CONCLUSIONS: Most traditional methods of maintaining trauma patient temperature during prehospital transport appear to be inadequate. Aggressive use of hot packs, a simple, inexpensive intervention to maintain thermostasis, deserves further study as a potential basic intervention for trauma patients.

Adolescent↗
PubMed2000

Broadband control of plate radiation using a piezoelectric, double-amplifier active-skin and structural acoustic sensing

The potential of a piezoelectric, double-amplifier active-skin with structural acoustic sensing (SAS) is demonstrated for the reduction of broadband acoustic radiation from a clamped, aluminum plate. The active-skin is a continuous covering of the vibrating portions of the plate with active, independently controllable piezoelectric, double-amplifier elements and is designed to affect control by altering the continuous structural radiation impedance rather than structural vibration. In simulation, acoustic models are sought for the primary and secondary sources that incorporate finite element methods. Simulation indicates that a total radiated power attenuation in excess of 10 dB may be achieved between 250 and 750 Hz with microphone error sensing, while under SAS the radiated power is reduced by nearly 8 dB in the same frequency range. In experiment, the adaptive feed forward filtered-x LMS (least mean square) algorithm, implemented on a Texas Instruments C40 DSP, was used in conjunction with the 6I6O control system. With microphone error sensing, 11.8-dB attenuation was achieved in the overall radiated power between 175 and 600 Hz, while inclusion of SAS resulted in a 7.3-dB overall power reduction in this frequency band.

Journal Article↗