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Biomedical subjects

M Mass

Publications and source records attributed to M Mass.

At least 19 recordsLinked to original sources
PubMed2005

Low-contrast letter acuity testing captures visual dysfunction in patients with multiple sclerosis.

OBJECTIVE: To evaluate concurrent and predictive validity for low-contrast letter acuity (L-CLA) testing as a candidate visual component for the Multiple Sclerosis Functional Composite (MSFC). METHODS: L-CLA testing was conducted in two MS patient cohorts. In the MSFC Validation Study, 137 participants from a Phase III trial of inteferon beta-1a (Avonex) for relapsing-remitting MS were followed. A second cohort included 65 patients with secondary progressive MS who participated in a substudy of the International MS Secondary Progressive Avonex Controlled Trial (IMPACT). The total number of letters read correctly at four contrast levels (100, 5, 1.25, and 0.6%) was correlated with Expanded Disability Status Scale (EDSS), MSFC, Sickness Impact Profile, Multiple Sclerosis Quality of Life Inventory, and brain parenchymal fraction (BPF), as determined by MRI. RESULTS: Low- and high-contrast letter acuity scores correlated with BPF at follow-up in the MSFC Validation Study (5%: r = 0.40, p < 0.0001; 100%: r = 0.31, p = 0.0002). L-CLA also correlated with EDSS (5%: r = -0.35, p < 0.0001; 1.25%: r = -0.26, p = 0.0003) and MSFC (5%: r = 0.47, p < 0.0001; 1.25%: r = 0.45, p < 0.0001). In the IMPACT Substudy, change in L-CLA scores from baseline to year 1 predicted subsequent change in the EDSS from year 1 to 2 at the 5% (p = 0.0142) and the 1.25% (p = 0.0038) contrast levels, after adjusting for change in MSFC scores from baseline to year 1. CONCLUSIONS: Low-contrast letter acuity (L-CLA) scores demonstrate concurrent and predictive validity in patients with relapsing-remitting and secondary progressive multiple sclerosis (MS). L-CLA testing provides additional information relevant to the MS disease process that is not entirely captured by the Multiple Sclerosis Functional Composite.

Adult↗
PubMed2005

A highly immunogenic trivalent T cell receptor peptide vaccine for multiple sclerosis.

BACKGROUND: T cell receptor (TCR) peptide vaccination is a novel approach to treating multiple sclerosis (MS). The low immunogenicity of previous vaccines has hindered the development of TCR peptide vaccination for MS. OBJECTIVE: To compare the immunogenicity of intramuscular injections of TCR BV5S2, BV6S5 and BV13S1 CDR2 peptides in incomplete Freunds adjuvant (IFA) with intradermal injections of the same peptides without IFA. METHODS: MS subjects were randomized to receive TCR peptides/IFA, TCR peptides/saline or IFA alone. Subjects were on study for 24 weeks. RESULTS: The TCR peptides/IFA vaccine induced vigorous T cell responses in 100% of subjects completing the 24-week study (9/9) compared with only 20% (2/10) of those receiving the TCR peptides/saline vaccine (P =0.001). IFA alone induced a weak response in only one of five subjects. Aside from injection site reactions, there were no significant adverse events attributable to the treatment. CONCLUSIONS: The trivalent TCR peptide in IFA vaccine represents a significant improvement in immunogenicity over previous TCR peptide vaccines and warrants investigation of its ability to treat MS.

Adult↗
PubMed2004

Randomized controlled trial of yoga and exercise in multiple sclerosis.

OBJECTIVE: To determine the effect of yoga and of aerobic exercise on cognitive function, fatigue, mood, and quality of life in multiple sclerosis (MS). METHODS: Subjects with clinically definite MS and Expanded Disability Status Score less than or equal to 6.0 were randomly assigned to one of three groups lasting 6 months: weekly Iyengar yoga class along with home practice, weekly exercise class using a stationary bicycle along with home exercise, or a waiting-list control group. Outcome assessments performed at baseline and at the end of the 6-month period included a battery of cognitive measures focused on attention, physiologic measures of alertness, Profile of Mood States, State-Trait Anxiety Inventory, Multi-Dimensional Fatigue Inventory (MFI), and Short Form (SF)-36 health-related quality of life. RESULTS: Sixty-nine subjects were recruited and randomized. Twelve subjects did not finish the 6-month intervention. There were no adverse events related to the intervention. There were no effects from either of the active interventions on either of the primary outcome measures of attention or alertness. Both active interventions produced improvement in secondary measures of fatigue compared to the control group: Energy and Fatigue (Vitality) on the SF-36 and general fatigue on the MFI. There were no clear changes in mood related to yoga or exercise. CONCLUSION: Subjects with MS participating in either a 6-month yoga class or exercise class showed significant improvement in measures of fatigue compared to a waiting-list control group. There was no relative improvement of cognitive function in either of the intervention groups.

Adult↗
PubMed2001

Diminished frequency of interleukin-10-secreting, T-cell receptor peptide-reactive T cells in multiple sclerosis patients might allow expansion of activated memory T cells bearing the cognate BV gene.

T cells responsive to T-cell receptor (TCR) determinants may regulate pathogenic Th1 responses in patients with multiple sclerosis (MS) through interleukin (IL)-10-dependent bystander suppression. In this study, innate IL-10- and interferon (IFN)-gamma-secreting T cells responsive to TCR peptides were quantified in peripheral blood mononuclear cells of MS patients and healthy controls (HC) using the ELISPOT assay. Most HC had vigorous IL-10 but low IFN-gamma frequencies to BV5S2 and BV6S1 peptides. In contrast, MS patients had significantly lower IL-10 frequency responses to the TCR peptides but normal responses to concanavalin A. Patients undergoing TCR-peptide vaccination had moderate responses that fluctuated in concert with vaccination. In an MS patient and HC, expression of BV6S1 by activated memory T cells was inversely associated with the presence of IL-10-secreting BV6S1-reactive T cells. These results suggest that MS patients have diminished frequencies of innate TCR-reactive T cells that may allow oligoclonal expansion of activated autoreactive Th1 effector cells expressing cognate V genes.

Adult↗
PubMed1999

Myelin basic protein-specific T lymphocytes induce chronic relapsing experimental autoimmune encephalomyelitis in lymphocyte-deficient (SCID) mice.

Myelin basic protein (BP)-specific T lymphocyte cell lines were selected from the lymph nodes (LN) of BP-immunized, H-2d, CXJ-1 mice prior to the onset of clinical disease. These CD4+ T cells induced severe acute experimental autoimmune encephalomyelitis (EAE) in MHC-compatible (H-2d), lymphocyte-deficient (SCID) mice (C.B-17scid/scid). The incidence of disease was much higher in immunodeficient SCID mice (71%) than in syngeneic immunocompetent CXJ-1 mice (5%). SCID mice with EAE had an acute progressive paralytic disease with inflammation and myelin loss detected in the spinal cord. Eighty-six percent (12/14) of mice followed for more than 2 weeks had 1 or more relapses of EAE. These results demonstrate that clinical remission and relapse of EAE can be induced by the single adoptive transfer of a LN-derived BP-specific T cell line in the absence of host-derived effector and regulatory lymphocytes. Furthermore, the data demonstrate that the pathogenic potential of BP-specific T cells is greater in lymphocyte-deficient SCID mice compared with immunocompetent mice, suggesting that autoreactive T cells are controlled by potent inhibitory mechanisms associated with regulatory lymphocytes. These results are relevant to mechanisms of disease remission and relapse mediated by lymphocytes involved in paralytic inflammatory diseases such as multiple sclerosis (MS).

Animals↗
PubMed1998

Caring for the graduate from the neonatal intensive care unit. At home, in the office, and in the community.

This article focuses on recent progress in the understanding of optimal care for the neonatal intensive care unit (NICU) graduate in three domains that have relevance to primary care pediatricians: the concept of developmentally supportive care for the immature central nervous system of fragile premature infants; an understanding of the function and systems of community-based early intervention available for medically complex, developmentally challenged and at-risk infants; and the management of technology-dependent children at home.

Aftercare↗
PubMed1997

Aminophylline as an adjunct to standard advanced cardiac life support in prolonged cardiac arrest.

STUDY HYPOTHESIS: We hypothesized that the addition of aminophylline to Advanced Cardiac Life Support (ACLS) interventions would improve the initial resuscitation success rate in an animal model of prolonged cardiac arrest. METHODS: We used a double-blind, placebo-controlled, randomized-block design with a follow-up open-label uncontrolled phase. We studied 24 female domestic mixed-breed swine (body mass, 20 to 25 kg). After electrical induction of ventricular fibrillation, animals were subjected to 8 minutes of no-flow cardiac arrest followed by 1 minute of mechanical ventilation and closed-chest compressions. Nine minutes after arrest, equal numbers of swine received 6 mg/kg intravenous aminophylline (treatment group) and a saline solution placebo (control group), another minute of basic CPR, and standardized ACLS interventions beginning at 10 minutes. Initial resuscitation efforts were continued for at least 20 minutes. In all animals, if initial efforts failed, 6.0 mg/kg intravenous aminophylline, open label, and 10 minutes of additional resuscitation were administered. The primary outcome variables were return of spontaneous circulation (ROSC) and 1-hour survival. We compared groups with the two-tailed Fisher exact test. RESULTS: ROSC occurred in 4 of 12 animals in the treatment group (33%) and 3 of 12 in the control group (25%) (P=.50). Late administration of aminophylline did not result in ROSC in any animal. Survival to 1 hour was greater in the treatment group (4 of 12, 33%) than in the control group (1 of 12, 8%) (P=.16). CONCLUSION: Addition of aminophylline to standard ACLS interventions did not increase the incidence of ROSC or the 1-hour survival rate in a swine model of prolonged cardiac arrest.

Aminophylline↗
PubMed1997

Long-term toxicity and neuropathology associated with the sequencing of cranial irradiation and enhanced chemotherapy delivery.

OBJECTIVE: The goal was to evaluate, at 1 year, 75 Long-Evans rats for survival rates and toxicity associated with the sequencing of cranial irradiation and enhanced chemotherapy delivery. METHODS: Seventy-five Long-Evans rats were randomized into four groups and evaluated at 1 year for survival rates and toxicity associated with the sequencing of cranial irradiation and enhanced chemotherapy delivery. Radiation (2,000 cGy) was administered as a single fraction, by using parallel opposed portals, 30 days before chemotherapy (Group 1), 24 hours before chemotherapy (Group 2), 30 days after chemotherapy (Group 3), or without chemotherapy or without radiation (control group, Group 4). Five subgroups within each treatment group included rats receiving intra-arterially administered methotrexate (1 g/m2) or intravenously administered etoposide (200 mg/m2) combined with intra-arterially administered carboplatin (200 mg/m2), administered with or without osmotic blood-rain barrier disruption, and a group receiving normal saline solution after blood-brain barrier disruption. RESULTS: There was a significant increase in total toxic effects when the three experimental groups were compared with the control group (P = 0.001, 0.006, and 0.013 for Groups 1, 2, and 3, respectively). All groups receiving radiation and chemotherapy (particularly carboplatin and etoposide) had an increased incidence of hind limb paralysis, resembling experimental allergic neuritis (P = 0.053). Statistical analysis showed a trend toward increased mortality rates in Group 1 (antecedent radiation), compared with the control group (P = 0.082), and an increased incidence of intracerebral calcification (P = 0.019). No differences in mortality rates were observed for Group 2 or 3, compared with the control group. CONCLUSION: Radiation before chemotherapy was a more toxic sequence and, surprisingly, carboplatin/etoposide administered in combination with radiotherapy was more detrimental than methotrexate. Additional studies are in progress to evaluate the toxicity and efficacy of sequences of cranial irradiation and enhanced chemotherapy in tumor-bearing rats.

Animals↗
PubMed1997

What interventions do nurses use in long-term care?

This study validated that the Nursing Interventions Classification is appropriate for use in long term care. It is comprehensive and supports the interventions nurses need and use in long term care practice. There is a need for additional research to determine its usefulness in other settings and with other patient populations, as well as studies based on practice versus respondent's opinion. For the elderly clients alone, there are many settings in which to verify use of NIC; including residential, assisted living, independent living, intermediate care units, skilled care units, low-stimulus units, hospice, adult day care and the emerging specialty units. An important next step will be to note the similarities and differences of interventions used across these settings to discern practice setting needs.

Adult↗
PubMed1996

Treatment of relapsing autoimmune encephalomyelitis with T cell receptor V beta-specific antibodies when proteolipid protein is the autoantigen.

Monoclonal antibodies (mAbs) directed against the V beta chain of the T cell receptor (TCR) of pathogenic T cells have been used to treat acute murine experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (BP). We evaluated anti-V beta mAb for the treatment of relapsing EAE (R-EAE) induced in SJL/J mice by the myelin proteolipid protein (PLP) peptide 139-151. Spinal cord mononuclear cells isolated from mice immunized for R-EAE with PLP 139-151 were shown to express a predominance of V beta 2 and V beta 17 during acute and relapsing disease. T cell lines specific for PLP 139-151 were magnetically sorted to express 80-90% V beta 2. These V beta 2-enriched lines induced typical relapsing demyelinating EAE in naive recipient mice. SJL/J mice with R-EAE induced by a PLP 139-151-specific T cell line expressing 88% V beta 2 were treated with anti-V beta 2 mAb. Anti-V beta 2 mAb markedly reduced clinical and histological disease severity when given at the time of cell transfer or when given at clinical disease onset. In contrast, anti-V beta mAbs showed only a mild clinical effect on R-EAE induced by immunization with PLP 139-151 or R-EAE transferred by a PLP 139-151-specific T cell line expressing multiple V beta s. A cocktail of mAbs directed against V beta 2, V beta 4, and V beta 17 significantly reduced the numbers of spinal cord T cells expressing these V beta s during acute EAE but had little effect on disease course, suggesting that pathogenic T cells expressing other V beta s were producing disease. These findings may have implications for the treatment of multiple sclerosis with V beta-selective therapy.

Analysis of Variance↗
PubMed1996

Treatment of multiple sclerosis with T-cell receptor peptides: results of a double-blind pilot trial.

A T-cell receptor (TCR) peptide vaccine from the V beta 5.2 sequence expressed in multiple sclerosis (MS) plaques and on myelin basic protein (MBP)-specific T cells boosted peptide-reactive T cells in patients with progressive MS. Vaccine responders had a reduced MBP response and remained clinically stable without side effects during one year of therapy, whereas nonresponders had an increased MBP response and progressed clinically. Peptide-specific T helper 2 cells directly inhibited MBP-specific T helper 1 cells in vitro through the release of interleukin-10, implicating a bystander suppression mechanism that holds promise for treatment of MS and other autoimmune diseases.

Adult↗
PubMed1995

T cells with encephalitogenic potential from multiple sclerosis patients and Lewis rats fail to induce disease in SCID mice following intracisternal injection.

Intracisternal (IC) transfer of cerebrospinal fluid (CSF) mononuclear cells from multiple sclerosis (MS) patients has been reported by others to induce an 'MS-like pathology' in severe combined immunodeficient (SCID) mice. We injected cells from several sources intracisternally into SCID mice and assessed the recipients for clinical and histological disease. CSF cells and myelin basic protein (BP)-specific T lymphocytes from MS patients failed to induce clinical or histological disease following IC injection in SCID mice. Similarly, encephalitogenic BP-specific T cells from Lewis rats were unable to induce disease after IC injection in either SCID mice or Lewis rats, even at cell numbers which induced experimental autoimmune encephalomyelitis in Lewis rats following intraperitoneal (IP) injection. In contrast, naive Lewis rat splenocytes, which were capable of inducing lethal graft-versus-host (GVH) disease following IP transfer in SCID mice, induced paralysis and histopathological changes following IC transfer in SCID mice. We conclude that MS CSF cells do not typically transfer disease into SCID mice following IC injection. Furthermore, it appears likely that neuropathological disease following IC transfer of cells reflects the potential of the transferred cells for inducing GVH disease. Specific recognition of neuroantigens by T cells, as occurs in EAE, is probably not involved in the transfer of paralytic disease by IC transferred MS patient CSF cells.

Animals↗
PubMed1995

Encephalitogenic T lymphocytes develop from SJL/J hematopoietic cells transplanted into severe combined immunodeficient (SCID) mice.

Previously, we constructed chimeras by injecting hematopoietic cells from experimental autoimmune encephalomyelitis (EAE)-susceptible SJL (H-2s) strain mice into severe combined immunodeficient (SCID) C.B-17scid/scid (H-2d) mice. These SCID mouse-SJL mouse hematopoietic cell chimeras developed passive EAE following adoptive transfer of PLP S139-151-specific SJL T lymphocyte line cells, but were resistant to active EAE induced by primary immunization with PLP S139-151. In order to gain an understanding of the encephalitogenic potential of transplanted hematopoietic progenitors in SCID mouse-SJL mouse chimeras, we attempted to induce EAE in hematopoietic chimeras constructed with or without an additional SJL fetal thymus implant. Chimeras with the thymus implant were susceptible to passive and active EAE while chimeras without the thymus implant were susceptible to passive but not active EAE. Encephalitogenic, CD4+, TCR+ T lymphocytes were selected in vitro from PLP S139-151-immunized, thymus-implanted chimeras. These results showed that hematopoietic SJL progenitors developed into antigen-presenting accessory cells and immunocompetent encephalitogenic T lymphocytes following transplantation into SCID mice. The development of primary immune reactivity depended on a fetal thymus implant for expression in SCID mouse-SJL mouse chimeras.

Amino Acid Sequence↗
PubMed1994

When a man encounters a woman, Satan is also present: clinical relationships in Bedouin society.

Professional encounters in Bedouin society between male therapists and their female clients are discussed in terms of the conflict between clinical precepts and Bedouin codes of social conduct. The effects of the conflict on the transference relationship are examined by means of case presentations, and rules of conduct acceptable in both the professional realm and Bedouin society are proposed as an avenue toward resolution.

Adult↗
PubMed1994

Focal and non-focal hepatic expression of placental glutathione S-transferase in carcinogen-treated rats.

Carcinogenesis develops in stages that have been operationally defined as initiation, promotion and progression. Although morphological end points have been described for detection and quantitation of these stages, to date initiation has been assessed only in the context of clonal growth in response to certain promoting agents. Initiated cells are morphologically indistinguishable from surrounding cells and early changes at the cellular level during initiation have not been clarified. One commonly used end point for the detection of preneoplastic hepatic lesions i their aberrant expression of the placental isozyme of glutathione S-transferase (PGST). Because single hepatocytes expressing PGST have been detected in aged rats and in those administered hepatocarcinogens, it has been suggested that such cells constitute a population of putatively initiated hepatocytes. In order to further elucidate the characteristics of single PGST-positive hepatocytes, we analyzed the number of these cells 2 and 18 weeks after various doses (0-100 mg/kg) of diethylnitrosamine (DEN) and of dimethylbenz[a]anthracene (DMBA). When determined 14 days after carcinogen administration, the number of single hepatocytes expressing PGST was greater after DEN administration (ranging from 0.8 +/- 0.3 per cm2 transection of liver at 1 mg/kg to 33.0 +/- 4.7 at 100 mg/kg) than after DMBA administration (ranging from 0.25 +/- 0.14 at 10 mg/kg to 3.03 +/- 0.5 at 100 mg/kg); none were detected in control rats of the same age. Additional rats were maintained on a basal diet or a basal diet plus phenobarbital for a further 4 month period. Whereas individual PGST-positive hepatocytes were only sporadically detected in rats treated with DMBA and maintained on a basal diet for 18 weeks, those rats placed on phenobarbital for 16 weeks had an even higher number of such PGST-positive hepatocytes than at 2 weeks after DMBA administration. In contrast, the dose-response curve observed for DEN-treated rats 18 weeks after carcinogen administration was similar to that observed 2 weeks after carcinogen treatment for both phenobarbital- and non-phenobarbital-treated rats. In addition, the number of single PGST-positive hepatocytes detected at 2 weeks was directly parallel to the number of altered hepatic foci expressing PGST 18 weeks after DEN administration. The dose-dependent induction of PGST-positive single hepatocytes after treatment with two hepatocarcinogens, the dose-dependent growth of altered hepatic foci (AHF) expressing PGST with phenobarbital administration and the parallel dose-response curve of single hepatocytes expressing PGST and later of AHF expressing PGST argue strongly for a precursor role of single PGST-positive cells in the development of AHF expressing PGST.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Incorporation of bromodeoxyuridine in glutathione S-transferase-positive hepatocytes during rat multistage hepatocarcinogenesis.

Cell proliferation is pivotal to all stages of the carcinogenesis process and is one of the primary characteristics of the promotion stage of cancer development. Both a two-stage model of initiation and promotion for analysis of early preneoplasia and a three-stage initiation-promotion-progression model of hepatocarcinogenesis were used to address the effect of the liver tumor-promoting agent phenobarbital (PB) on hepatic cellular proliferation. Male rats were subjected to a 70% partial hepatectomy and 10 mg diethylnitrosamine (DEN)/kg or the solvent alone and were administered PB for 4-8 months. Analysis of bromodeoxyuridine (BrdU) incorporation (1 h pulse) in liver within (focal) and not within (non-focal) altered hepatic foci (AHF) demonstrated a labeling index in AHF of 2% in DEN-initiated rats; the non-focal labeling index of placental glutathione S-transferase expressing hepatocytes was 0.3-0.6%. The focal labeling index was constant over the 8 month period of promotion. Inasmuch as one characteristic of promotion is the reversibility of the induced effects on clonal expansion of initiated cells, groups of rats initially promoted with PB were maintained in the absence of continued promotion for 4 or 8 months prior to being killed. Assessment of the focal labeling index after cessation of PB treatment indicated a drop in the index from 2.3% to 0.7%. When a progressor agent, ethylnitrosourea, was given at the time PB was discontinued for 4 or 8 months, a significant change in focal labeling index was not observed relative to the index in AHF when the animals were killed immediately after 8 months of PB promotion. Thus, cell proliferation plays an integral role in both the promotion and progression stages of multistage rat hepatocarcinogenesis and is influenced by administration of promoting and progressor agents.

Animals↗
PubMed1993

Detection of proliferating cell nuclear antigen in gliomas and adjacent resection margins.

We describe a technique for estimating the number of proliferating cells in gliomas and adjacent resection cavities after tumor removal. Proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with the cell cycle. Anti-PCNA antibody staining provides a semiquantitative estimate of the number of proliferating cells found in fixed tissue embedded in paraffin. The extent of the staining of tumor cells of glioblastoma multiforme, anaplastic astrocytomas, low-grade gliomas, and other lesions of the brain with anti-PCNA antibody is correlated with the histological diagnosis. In addition, the labeling of the margins after resection of gliomas and other lesions with anti-PCNA antibody is also associated with the histological diagnosis of the lesion. This technique may be useful in estimating the "biological" extent of resection and in predicting the recurrence patterns of gliomas.

Adolescent↗