Biomedical subjects

K M Martin

Publications and source records attributed to K M Martin.

At least 19 recordsLinked to original sources

PubMed2003

Dynorphin A toxicity in striatal neurons via an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor mechanism.

Dynorphin A (1-17) is an endogenous opioid peptide that is antinociceptive at physiological concentrations, but in excess can elicit a number of pathological effects. Both kappa-opioid and N-methyl-D-aspartate receptor antagonists modulate dynorphin toxicity, suggesting that dynorphin is acting directly or indirectly through these receptor types. We found in spinal cord neurons that the neurotoxic effects of dynorphin A and several dynorphin-derived peptide fragments are largely mediated by N-methyl-D-aspartate receptors. Despite these findings, aspects of dynorphin A toxicity could not be accounted for by opioid or N-methyl-D-aspartate receptor mechanisms. To address this issue, neurons enriched in kappa-opioid, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors were isolated from embryonic day-15 mouse striata and the effects of extracellularly administered dynorphin A (1-17) and (13-17) on neuronal survival were examined in vitro. Unlike spinal cord neurons, N-methyl-D-aspartate receptors mature later than alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptors in striatal neurons, thus providing a strategy to elucidate non-N-methyl-D-aspartate receptor-mediated mechanisms of toxicity. Time-lapse photography was used to repeatedly follow the same neurons before and during experimental treatments. Dynorphin A (1-17 or 13-17; 10 microM) caused significant neuronal losses after 48 to 72 hours versus untreated controls. Dynorphin A or A (13-17) toxicity was unaffected by the opioid receptor antagonist naloxone (10 microM) or by dizocilpine (10 microM). In contrast, the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline- 2,3-dione (10 microM) significantly attenuated only dynorphin A (1-17)-induced neuronal losses and not that induced by dynorphin A (13-17). Dynorphin A (1-17) toxicity was accompanied by a proportional loss of R2 and R3 subunits of the AMPA receptor complex, but not non-N-methyl-D-aspartateR1, expressing neurons and was mimicked by the ampakine 1-(1,4-benzodioxan-6-ylcarbonyl)piperidine. Although it is unclear whether dynorphin A activates alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptors directly or indirectly via glutamate release, our culture conditions do not support glutamate retention or accumulation. Our findings suggest that dynorphin A (1-17) can exert toxic effects on striatal neurons via an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor mechanism.

Animals↗

PubMed2001

Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat protein in striatal neurons in vitro.

Human immunodeficiency virus (HIV) infection selectively targets the striatum, a region rich in opioid receptor-expressing neural cells, resulting in gliosis and neuronal losses. Opioids can be neuroprotective or can promote neurodegeneration. To determine whether opioids modify the response of neurons to human immunodeficiency virus type 1 (HIV-1) Tat protein-induced neurotoxicity, neural cell cultures from mouse striatum were initially characterized for mu and/or kappa opioid receptor immunoreactivity. These cultures were continuously treated with morphine, the opioid antagonist naloxone, and/or HIV-1 Tat (1-72) protein, a non-neurotoxic HIV-1 Tat deletion mutant (TatDelta31-61) protein, or immunoneutralized HIV-1 Tat (1-72) protein. Neuronal and astrocyte viability was examined by ethidium monoazide exclusion, and by apoptotic changes in nuclear heterochromatin using Hoechst 33342. Morphine (10nM, 100nM or 1microM) significantly increased Tat-induced (100 or 200nM) neuronal losses by about two-fold at 24h following exposure. The synergistic effects of morphine and Tat were prevented by naloxone (3microM), indicating the involvement of opioid receptors. Furthermore, morphine was not toxic when combined with mutant Tat or immunoneutralized Tat. Neuronal losses were accompanied by chromatin condensation and pyknosis. Astrocyte viability was unaffected. These findings demonstrate that acute opioid exposure can exacerbate the neurodegenerative effect of HIV-1 Tat protein in striatal neurons, and infer a means by which opioids may hasten the progression of HIV-associated dementia.

Animals↗

PubMed2001

Expression of Klf9 and Klf13 in mouse development.

Klf9 and Klf13 are members of the C(2)H(2) zinc finger family of transcription factors that are thought to be involved in regulating basal transcription. The mRNA localization of Klf9 and Klf13 during development was determined by in situ hybridization of mouse E8, E11, E13 and E16 embryo sections. The data showed that Klf9 and Klf13 are widely expressed at all the mouse embryo stages examined. Whilst the expression patterns of the two genes largely overlap there are differences in the localization or level of expression in some tissues. At E11, both genes are expressed in high levels in the cephalic mesenchyme whilst Klf13 and not Klf9 is expressed at high levels in the developing heart at E8 and E11. In the gut and bladder at E16, Klf13 is expressed in the epithelial cell layer whereas Klf9 is expressed in both the muscle and epithelial layers. Both Klf9 and Klf13 are expressed at high levels in the epidermis at E11, E13 and E16.

Animals↗

PubMed2001

The immunohistochemical detection of Mycoplasma bovis and bovine viral diarrhea virus in tissues of feedlot cattle with chronic, unresponsive respiratory disease and/or arthritis.

The purpose of this study was to determine the frequency of selected pathogens in the tissues of a group of feedlot cattle with chronic disease (most often respiratory disease and/or arthritis). Samples of lung and joint tissues from 49 feedlot animals that had failed to respond to antibiotic therapy were tested by immunohistochemical staining for the antigens of Mycoplasma bovis, Haemophilus somnus, Pasteurella (Mannheimia) hemolytica, and bovine viral diarrhea virus (BVDV). Mycoplasma bovis was demonstrated in over 80% of cases, including in 45% of joints and 71% of lungs tested. Mycoplasma bovis was the only bacterial pathogen identified in the joints. Haemophilus somnus and Pasteurella (Mannheimia) haemolytica were found in 14% and 23% of cases, respectively, and were confined to the lungs in all instances. Infection with BVDV was demonstrated in over 40% of cases. Mycoplasma bovis and BVDV were the most common pathogens persisting in the tissues of these animals that had failed to respond to antibiotic therapy.

Animals↗

PubMed2000

Evaluation of dietary and environmental risk factors for hyperthyroidism in cats.

OBJECTIVE: To identify dietary and environmental risk factors for hyperthyroidism in cats. DESIGN: Case-control study. ANIMALS: 100 cats with hyperthyroidism and 163 control cats. PROCEDURE: Medical records were examined, and owners completed a mailed questionnaire. Data collected included information regarding demographic variables, environmental exposures, and diet, including preferred flavors of canned cat food. RESULTS: Case cats were significantly less likely to have been born recently than control cats. Housing; exposure to fertilizers, herbicides, or plant pesticides; regular use of flea products; and presence of a smoker in the home were not significantly associated with an increased risk of disease, but cats that preferred fish or liver and giblets flavors of canned cat food had an increased risk. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats that prefer to eat certain flavors of canned cat food may have a significantly increased risk of hyperthyroidism.

Age Factors↗

PubMed2000

Mouse BTEB3, a new member of the basic transcription element binding protein (BTEB) family, activates expression from GC-rich minimal promoter regions.

Members of the three-zinc-finger family of transcription factors play an important role in determining basal transcription. We have cloned mouse BTEB3 (mBTEB3), a new member of the basic transcription element binding protein (BTEB) family, which is expressed in a wide variety of tissues. mBTEB3 activates transcription of the simian virus 40 early promoter (4-fold) and of the tissue-specific SM22alpha promoter (100-fold), suggesting that, like BTEB1 and Sp1, mBTEB3 is a basal transcription factor.

Amino Acid Sequence↗

PubMed2000

Gradient preemphasis calibration in diffusion-weighted echo-planar imaging.

This article describes a method which enables fast and objective pulse-sequence-specific preemphasis calibration, using standard pulse sequences and system hardware. The method is based on a k-space measurement technique, and has been applied to single-shot, diffusion-weighted, spin-echo, echo-planar imaging (DW-SE-EPI), which is particularly sensitive to eddy-current-induced image distortions. The efficiency of the technique was demonstrated not only by the reduction of eddy-current fields to a negligible level using full preemphasis compensation, but also by the fact that adjustment of the slow time-base alone sufficed for the practical elimination of image distortions in the DW-SE-EPI images and the subsequent diffusion tensor maps (in a phantom and a human brain). By seeking to eliminate directly the effect of eddy-current-induced phase shifts during the EPI data collection, the method is free of the complications and restrictions associated with other eddy-current correction techniques for DW-SE-EPI (such as acquisition of additional calibration scans, intense postprocessing, extensive pulse-sequence modifications), making their use redundant.

Brain↗

PubMed1999

The reduction of the sorting bias in the eigenvalues of the diffusion tensor.

One of the most intrinsic quantities when measuring the diffusion properties of a system is the set of principal diffusivities, which represents diffusion along the fibre axes. System noise is a well-known cause of systematic sorting bias when closely spaced diffusivities are ordered according to their magnitude and leads to their inaccurate estimation. This paper describes a new method for the ordering of the principal diffusivities in which local fibre directional coherence was used as a basis for sorting. The method was applied and tested in computer simulations and experimental data acquired in an isotropic water phantom and healthy human brain. Our results demonstrate that this method leads to significant reduction in the sorting bias in comparison to other techniques and thus a more accurate estimation of the eigenvalues. The method is advantageous over other proposed alternatives to the conventional magnitude sorting method because it is not reliant on a large region-of-interest averaging scheme.

Anisotropy↗

PubMed1999

Immunohistochemical detection of canine distemper virus in haired skin, nasal mucosa, and footpad epithelium: a method for antemortem diagnosis of infection.

A reliable antemortem diagnostic method is needed for determining infection with canine distemper virus (CDV). The utility of immunohistochemical detection of CDV antigen was examined was examined for samples of nasal and footpad epithelium and haired skin in dogs with and without detectable CDV antigen in the lung and/or brain. Tissues from 57 dogs at risk of CDV infection were tested. Viral antigen was found in the lung and/or brain of 28 dogs. Among these dogs, viral antigen was demonstrated in the epithelial cells of the nasal mucosa in 24 of 27 dogs, in the footpad epithelium in 24 of 26 dogs, and in the haired skin of the dorsal neck in 26 of 27 dogs. Among the 29 dogs without CDV antigen in either the lung or brain, 1 dog had positive staining for viral antigen in the skin and nasal mucosa. Biopsies of haired skin of the dorsal neck, which is relatively simple to sample, can be used for immunohistochemical testing for acute and subacute infection with CDV.

Animals↗

PubMed1998

Interactive coronary MRI.

The acquisition of complete three-dimensional (3D), segmented gradient-echo data sets to visualize the coronary arteries can be both time consuming and sensitive to motion, even with use of multiple breath-holding or respiratory gating. An alternate hybrid approach is demonstrated here, in which real-time interactive imaging is first used to locate an optimal oblique coronary scan plane. Then, a limited number of contiguous slices are acquired around that plane within a breath-hold with use of two-dimensional (2D) segmented gradient-echo imaging. Dual inversion nulling is used to suppress fat and myocardium. Finally, if needed, a limited reformat of the data is performed to produce images from relatively long sections of the coronaries. This approach yields relatively rapid visualization of portions of the coronary tree. Several different methods are compared for interactively moving the scan plane.

Coronary Angiography↗

PubMed1998

Lesions and distribution of viral antigen following an experimental infection of young seronegative calves with virulent bovine virus diarrhea virus-type II.

During the past several years, acute infections with bovine viral diarrhea virus (BVDV) have been causally linked to hemorrhagic and acute mucosal disease-like syndromes with high mortality. The majority of BVDVs isolated in such cases have been classified as type II on the basis of genetic and antigenic characteristics. It was our objective to examine clinical disease, lesions and potential sites of viral replication, following experimental BVDV type II infection in young calves. On approximately day 35 after birth, calves that had received BVDV-antibody-negative colostrum were infected by intranasal inoculation of 5 x 10(5) TCID50 of BVDV type II isolate 24,515 in 5 mL of tissue culture fluid (2.5 mL/nostril). Calves were monitored twice daily for signs of clinical disease. Approximately 48-72 h after infection, all calves developed transient pyrexia (39.4-40.5 degrees C) and leukopenia. Beginning on approximately day 7 after infection, all calves developed watery diarrhea, pyrexia (40.5-41.6 degrees C), marked leukopenia (> or = 75% drop from preinoculation values), variable thrombocytopenia, and moderate to severe depression. Calves were euthanized on days 10, 11, or 12 after infection due to severe disease. Gross and histological lesions consisted of multifocal bronchointerstitial pneumonia (involving 10%-25% of affected lungs), bone marrow hypoplasia and necrosis, and minimal erosive lesions in the alimentary tract. Immunohistochemical staining for BVDV revealed widespread viral antigen usually within epithelial cells, smooth muscle cells and mononuclear phagocytes in multiple organs, including lung, Peyer's patches, gastric mucosa, thymus, adrenal gland, spleen, lymph nodes, bone marrow, and skin. This BVDV type II isolate caused rapidly progressive, severe multisystemic disease in seronegative calves that was associated with widespread distribution of viral antigen and few gross or histological inflammatory lesions.

Animals↗

PubMed1997

Giant intracranial aneurysm obliteration using deep hypothermic circulatory arrest.

Giant intracranial aneurysms pose significant technical problems for the neurosurgical team. Because of the location and structure of these lesions, the risks associated with traditional surgical techniques are usually unacceptable. Although aneurysm clipping using deep hypothermic circulatory arrest was first described 30 years ago, it was nearly abandoned because of poor outcomes associated with the systemic and cardiac complications of extracorporeal circulation. Advances in cardiopulmonary bypass techniques have inspired renewed interest in the use of this method in surgery for intracranial aneurysm. Deep hypothermic circulatory arrest, using low-flow states, has yielded exceptional patient outcomes. This increasingly popular means of management provides unique challenges to the neurosurgical health care team. Understanding the pre-, intra-, and postoperative care of these patients is imperative for neurosurgical nurses of the twenty-first century.

Heart Arrest, Induced↗

PubMed1996

Use of immunohistochemistry and polymerase chain reaction for detection of oncornaviruses in formalin-fixed, paraffin-embedded fibrosarcomas from cats.

OBJECTIVE: To determine whether there was intralesional infection or expression of FeLV or feline sarcoma virus in suspected vaccine-associated fibrosarcomas in cats. DESIGN: Prospective case series. SAMPLE POPULATION: 130 suspected vaccine-associated fibrosarcomas from cats and 1 multicentric fibrosarcoma from 1 cat. PROCEDURE: Excisional biopsy specimens were fixed in formalin and embedded in paraffin. Expression of FeLV antigen was assessed, using a polyclonal goat anti-FeLV glycoprotein 70 (gp 70) serum and an avidinbiotin immunoperoxidase staining technique. The FeLV genome was detected with a polymerase chain reaction (PCR), using primers targeted to a conserved sequence in the untranslated region of the long terminal repeat (LTR) of the FeLV. RESULTS: FeLV gp 70 and LTR sequence were detected in a multicentric fibrosarcoma. All 130 of the suspected vaccine-associated fibrosarcomas were FeLV gp 70 negative on the basis of immunohistochemical test results: 100 fibrosarcomas also were examined by use of PCR and were negative for FeLV LTR region. CLINICAL IMPLICATIONS: Exogenous retroviruses, FeLV, and feline sarcoma virus were not detected in these suspected vaccine-associated fibrosarcomas, using immunohistochemistry and PCR. Additional testing will be required to determine the nature of genomic alterations that are involved in the oncogenesis of vaccine-associated fibrosarcomas in cats.

Animals↗

PubMed1996

Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder.

BACKGROUND: We sought to determine in a new patient sample whether symptomatic improvement in obsessive-compulsive disorder treated with behavior modification is accompanied by significant changes in glucose metabolic rates in the caudate nucleus, measured with positron emission tomography, as seen in a previous study. Second, by combining samples from this and the previous study, we also examined whether there were pathologic correlational relationships among brain activity in the orbital cortex, caudate nucleus, and thalamus that obtained before behavioral treatment of obsessive-compulsive disorder, but that decreased significantly with symptom improvement. METHODS: Nine patients with obsessive-compulsive disorder were studied with positron emission tomography before and after 10 weeks of structured exposure and response prevention behavioral and cognitive treatment. Results were analyzed both alone and combined with those from nine similar subjects from the previous study. RESULTS: Behavior therapy responders had significant (P < .05) bilateral decreases in caudate glucose metabolic rates that were greater than those seen in poor responders to treatment. Before treatment, there were significant correlations of brain activity between the orbital gyri and the head of the caudate nucleus and the orbital gyri and the thalamus on the right. These correlations decreased significantly after effective treatment. CONCLUSIONS: These results replicate and extend previous findings of changes in caudate nucleus function with behavior therapy for obsessive-compulsive disorder. A prefrontal cortico-striato-thalamic brain system is implicated in mediation of symptoms of obsessive-compulsive disorder.

Adult↗

PubMed1996

Predictors of family functioning and change 3 years after traumatic brain injury in children.

OBJECTIVES: To examine changes in family functioning from injury to 3 years after pediatric traumatic brain injury; to determine factors most predictive of family outcomes at 3 years and variables that promote positive outcomes and changes over time. DESIGN: Prospective cohort study. SETTING: Two regional tertiary care centers: cases followed for 3 years into community. PARTICIPANTS: Families of 81 children, ages 6 to 15 years, who sustained closed head injury and loss of consciousness (mild = 43, moderate = 20, severe = 18), consecutively enrolled over 15 months. MAIN OUTCOME MEASURES: Family Environment Scale, Family Assessment Device, Family Inventory of Life Events, Health Insurance Survey-General Well-Being, NYU Problem Checklist for Significant Others, Family Interview Rating Scale, Family Global Assessment Scale. All were obtained initially and at 3 months, 1 year, and 3 years postinjury. Predictor variables were selected from the instruments above, as well as from the parent and teacher versions of the Child Behavior Checklist, socioeconomic status, and injury severity. RESULTS: Preinjury functioning was the best predictor of 3-year outcomes. Fewer changes in family functioning were reported over 3 years in the mild or moderate groups, whereas more deterioration occurred in the severe group. At 3 years, one third to one half of parents in either the moderate or severe groups reported medium to high strain in 19 of 34 problem areas. Low levels of family control and high levels of expressiveness correlated with better outcomes for severe group. Positive change for the severe group was marked by better preinjury levels of communication, expressiveness, problem solving, use of resources, role flexibility, greater activity orientation, and less conflict, control, and stress. Preinjury variables and severity explained from 26% to 69% of the variation in 3-year outcomes. CONCLUSIONS: Families at risk for poorer outcomes can be prospectively identified and should be supported and encouraged in their efforts to develop new coping resources.

Adaptation, Psychological↗

PubMed1996

A preliminary study of partial hospital management of severe obsessive-compulsive disorder.

OBJECTIVE: The study examined the effectiveness of a partial hospital treatment program combining behavioral therapy, medication, and psychosocial intervention for severe and treatment-resistant obsessive-compulsive disorder. METHODS: A total of 58 patients with a primary diagnosis of obsessive-compulsive disorder who underwent treatment in a partial hospital program were assessed at baseline, at program discharge, and at six-, 12-, and 18-month follow-ups. Obsessive-compulsive symptoms, depression, anxiety symptoms, and global functioning were rated. RESULTS: The majority of patients (71 percent) met the criterion for a successful outcome, which was a 25 percent decrease in score on the Yale-Brown Obsessive Compulsive Scale (YBOCS). Fifty-five percent finished the program with YBOCS scores of 16 or less, indicating only mild symptoms. Most of these patients sustained their improvement at six, 12, and 18 months after discharge, and many showed further improvement with continued outpatient management. CONCLUSIONS: The partial hospital treatment program for obsessive-compulsive disorder appears to be an effective intervention that should be implemented and investigated further.

Adolescent↗

PubMed1995

Rate of growth of Pseudomonas fluorescens in donated blood.

AIMS: To examine how delayed refrigeration of blood affects the growth of Pseudomonas fluorescens, one of the two most important causes of sepsis resulting from transfusion of contaminated blood. METHODS: Two donations of whole blood were each divided into three aliquots and inoculated with 5-10 cfu/ml of a P fluorescens strain from a case of transfusion associated sepsis. From each donation, one aliquot was placed at 4 degrees C, one was held at 20 degrees C for six hours prior to refrigeration and the third was held at 20 degrees C for 24 hours prior to refrigeration. Samples were aseptically withdrawn over 17 days and bacterial counts were determined using a pour plate technique. RESULTS: The rate of growth of P fluorescens in blood at 20 degrees C was increased compared with blood at 4 degrees C. At 24 hours the aliquots held at 20 degrees C for six and 24 hours had, respectively, 174 and 29,000 cfu/ml compared with 15 cfu/ml in aliquots held at 4 degrees C. There was no evidence of increased killing of P fluorescens at the higher temperature. CONCLUSIONS: These results suggest that blood for transfusion should be refrigerated as soon as possible after collection.

Blood↗

PubMed1994

Comparison of indices of traumatic brain injury severity as predictors of neurobehavioral outcome in children.

This study examined the ability of early measures of traumatic brain injury (TBI) severity to predict neurobehavioral and functional skill outcomes shortly after injury and at 1 year postinjury. Ninety-eight children aged 6 to 15 years with TBI were consecutively identified on presentation to two regional medical centers. Ten measures of TBI severity were subsequently administered: initial Glasgow Coma Scale (motor, eye, verbal, and total GCS), duration of loss of consciousness, Abbreviated Injury Scale Head score, GCS motor score at 3 days postinjury, days to reach a total GCS score of 15, days to reach a GCS motor score of six, and duration of posttraumatic amnesia (days to reach a 75% performance on the Children's Orientation and Amnesia Test [COAT]). Cases were matched individually with controls on the basis of age, gender, school grade, the classroom teacher's assessment of pre-morbid level of academic performance in reading and arithmetic, and pre-morbid behavior. Both groups received intellectual, neuropsychologic, academic, and functional skill assessments three weeks after the case achieved full orientation and 1 year later. The indices of injury severity that were most predictive of both early and 1-year outcome across all neurobehavioral and functional measures were (1) days to an age-adjusted 75% performance on the COAT, (2) days to a GCS score of 15, and (3) initial total GCS score. For most outcome areas, a single measure of severity predicted outcome almost as well as multiple measures. However, early and 1-year academic performance and 1-year memory performance were best predicted by considering multiple indices of brain injury severity. The GCS verbal and motor scores were better predictors of outcome than the GCS eye score. However, consideration of individual GCS subscores did not improve upon prediction of outcome versus the GCS total score. These results provide strong validation for the use of duration of posttraumatic amnesia, measured by the COAT, as a measure of TBI severity and a significant indicator of neurobehavioral and functional outcome in children.

Activities of Daily Living↗