Biomedical subjects

M Hartman

Publications and source records attributed to M Hartman.

At least 19 recordsLinked to original sources

PubMed2003

MR detectability and appearance of small experimental intracranial hematomas at 1.5 T and 0.5 T. A 6-7-month follow-up study.

PURPOSE: To investigate the detectability and appearance of small experimental intracranial hemorrhages on MR at 0.5 T and 1.5 T in a long-term follow-up. MATERIAL AND METHODS: Autologous blood (1 ml) was injected into the brain of 7 rabbits to create intraparenchymal hematomas. The injected blood leaked partially into the cerebrospinal fluid (CSF) spaces. MR imaging at 0.5 T and 1.5 T were performed immediately before and after hematoma creation, at 2 weeks and monthly up to 6 or 7 months using T1-, proton density- and T2-weighted (w) spin-echo (SE), FLAIR and T2*-w gradient echo (GE) pulse sequences. RESULTS: Blood was detected both in the brain and in the CSF spaces of all animals during the first hours after hematoma creation at 1.5 T. In the last examination after 6-7 months, the T2*-w GE sequences still showed residues of the intraparenchymal hematomas in all the rabbits at 1.5 T, but the signal pattern was not specific for the age of the hematomas. SE and FLAIR sequences were insensitive. The histopathology revealed iron deposits in all brains. CONCLUSION: Residues of small intraparenchymal hematomas can be seen for months with T2*-w GE sequences on brain MR imaging at 1.5 T. The age of the microhematomas cannot be estimated with MR imaging.

Animals↗

PubMed2002

Cost-effectiveness analysis of a psoriasis care instruction programme with dithranol compared with UVB phototherapy and inpatient dithranol treatment.

BACKGROUND: This study was part of a large national cost-effectiveness analysis, and was funded by the National Fund for Investigational Medicine of the Health Care Insurance Board. OBJECTIVE: To compare the costs of treatment of moderate to severe psoriasis by dithranol short contact therapy in a care instruction programme (short contact therapy) with ultraviolet B phototherapy (UVB) and inpatient dithranol treatment (inpatient treatment), and relate these costs to treatment effectiveness. METHODS: An open randomized controlled multicentre study was performed. The costs (both medical and non-medical) were calculated for the following periods: during treatment, per month during remission, after a relapse, and following an unsuccessful treatment. The effectiveness measures were the clinical response rate and the number of clearance days during follow-up. RESULTS: The data from 216 patients were analysed. The mean overall costs per patient during treatment were euro;1641, euro;1258 and euro;7706 for short contact treatment, UVB and inpatient treatment, respectively. During the clearance period the mean costs per month per patient were euro;19, euro;5 and euro;25, respectively. The clinical response rates were 57%, 57% and 85%, respectively. The mean number of clearance-days after short contact treatment was 160 [median 119; interquartile range (0-357)], which was not significantly different from the other two strategies: 211 clearance-days after inpatient treatment [241 (99-350)] and 136 clearance-days after UVB [81 (0-266)]. CONCLUSIONS: Short contact treatment is an attractive alternative for patients with moderate to severe psoriasis currently treated by inpatient treatment, as the costs of short contact treatment were significantly lower and the number of clearance days was comparable. Considering the higher costs, short contact treatment is not a first choice treatment when compared with UVB.

Administration, Topical↗

PubMed2002

Prognostic value of platelet derived growth factor alpha receptor expression in grade 2 astrocytomas and oligoastrocytomas.

OBJECTIVE: To determine whether the expression of platelet derived growth factor alpha receptor (PDGFRalpha) in low grade astrocytomas and oligoastrocytomas is associated with survival. METHODS: Formalin fixed and paraffin embedded tumour samples of 40 consecutive patients with supratentorial diffuse astrocytomas and oligoastrocytomas of WHO grade 2, resected between 1986 and 1993, were used for immunohistochemical staining. The fraction of tumour cells expressing PDGFRalpha protein was quantified and entered into univariate and multivariate survival analyses. Changes in PDGFalpha expression over time were analysed in seven patients in whom reoperations had been performed. RESULTS: Patients with a relatively high fraction of PDGFRalpha expressing cells had a more favourable outcome in both univariate (p = 0.04) and multivariate analyses (p = 0.02). Expression of PDGFRalpha was greater in oligoastrocytomas than in astrocytomas (p = 0.05). In four reoperated patients with histologically confirmed malignant transformation, there was a marked decrease in the number of cells expressing the receptor. CONCLUSIONS: There is an association between high PDGFRalpha expression and long survival time in patients with grade 2 astrocytomas and oligoastrocytomas. The findings suggest that expression of the receptor may be a useful prognostic marker in such patients.

Adult↗

PubMed2001

Positron emission tomography (11)C-methionine and survival in patients with low-grade gliomas.

BACKGROUND: Considerable numbers of patients with low-grade gliomas experience an early malignant course and may benefit from aggressive treatment. These patients are difficult to identify using established prognostic factors. A retrospective study was performed to determine whether the (11)C-methionine uptake in tumor is a survival factor in adult patients with supratentorial gliomas classified as World Health Organization Grade 2. METHODS: The authors identified 89 patients with histologically confirmed low-grade gliomas in whom an (11)C-methionine positron emission tomography (PET) scan had been performed as part of the diagnostic tumor investigation from 1983 to 1998. Clinical data were collected, and the PET scans were re-evaluated according to a fixed protocol. The (11)C-methionine uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analyses. RESULTS: At the end of the study, 49 patients (55.1%) had died. The median overall survival was 5.7 years. Low methionine uptake was significantly favorable in the multivariate survival analysis (P = 0.04) along with oligodendroglioma (P = 0.003). In the histologic subgroups, (11)C-methionine uptake was an important survival factor among patients with astrocytomas (P = 0.05) and oligodendrogliomas (P = 0.03). Tumor resection was a favorable prognostic factor in patients with high methionine uptake (P = 0.01) but not in patients with low uptake. CONCLUSIONS: Baseline (11)C-methionine PET is a prognostic indicator in patients with low-grade gliomas. The results imply that PET is a valuable tool in the clinical management of these patients and may assist in the selection of patients for therapy.

Adult↗

PubMed2001

Human peripheral blood eosinophils express stem cell factor.

Stem cell factor (SCF) or c-Kit ligand is a cytokine associated with the differentiation, survival, and activation of mast cells. Eosinophils have pleiotropic functions in several diseases and, together with mast cells, are key cells in allergy. Mast cell-eosinophil interactions can take place during the late and chronic phases of allergy. It was, therefore, investigated whether eosinophils can produce SCF and consequently influence mast cells. Human peripheral blood eosinophils variably expressed mRNA for the soluble and uncleaved forms of SCF (reverse transcription-polymerase chain reaction) and produced the 18.5-kd protein backbone of SCF (Western blot analysis). After overnight incubation in medium, eosinophils also produced SCF of higher molecular weight (42-45 kd) that might represent its glycosylated forms. Eosinophils expressed cytoplasmic SCF that colocalized with major basic protein (confocal laser microscopy). Freshly isolated eosinophils contained 8.9 +/- 1.7 pg SCF/10(6) (mean +/- SEM; enzyme-linked immunosorbent assay). Although overnight incubation of the eosinophils in either culture medium or in phorbol 12-myristate 13-acetate-calcium ionophore did not cause the secretion of SCF, the addition of chymase induced SCF release. In summary, it was demonstrated that human peripheral blood eosinophils are a source of SCF. These results may contribute to a better understanding of the interactions between eosinophils and mast cells in allergic inflammation.

Blood Proteins↗

PubMed2001

Economic evaluation of ventilation tubes in otitis media with effusion.

OBJECTIVE: To determine the costs and effectiveness of treatment with ventilation tubes as compared with watchful waiting in children with persistent otitis media with effusion. DESIGN: Randomized controlled trial. SETTING: Institutional practice. PATIENTS: A total of 187 young children (19 months old) with persistent bilateral otitis media with effusion. INTERVENTIONS: Treatment with ventilation tubes or watchful waiting. MAIN OUTCOME MEASURES: The time without effusion, language development, and the costs from a societal perspective during 1-year follow-up. RESULTS: The mean duration of effusion was 9.2 months in the watchful waiting group and 4.7 months in the ventilation tube group. The language development was comparable in both groups (0.7 month of improvement difference [95% confidence interval, -0.3 to 1.7 months] after correction for confounding variables). Because no statistically significant differences were found in the language development between the treatment groups, we performed a cost minimization analysis. The mean costs per child during 1 year of follow-up were 454 US dollars in the ventilation tube group and 120 US dollars in the watchful waiting group. On average, an additional investment of 334 US dollars per patient was needed for ventilation tube treatment. CONCLUSION: In the absence of differences in language development and in view of higher costs, treatment with ventilation tubes is not recommended as standard treatment in all young children with persistent otitis media with effusion traced by a population-based screening program.

Cost-Benefit Analysis↗

PubMed2001

Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To study the effect of folates on discontinuation of methotrexate (MTX) as single-drug antirheumatic treatment due to toxicity, to determine which type of adverse events are reduced, to study the effects on the efficacy of MTX, and to compare folic with folinic acid supplementation in a 48-week, randomized, double-blind, placebo-controlled trial. METHODS: Patients with active RA (n = 434) were randomly assigned to receive MTX plus either placebo, folic acid (1 mg/day), or folinic acid (2.5 mg/week). The initial MTX dosage was 7.5 mg/week; dosage increases were allowed up to a maximum of 25 mg/week for insufficient responses. Folate dosages were doubled once the dosage of MTX reached 15 mg/week. The primary end point was MTX withdrawal because of adverse events. Secondary end points were the MTX dosage and parameters of efficacy and toxicity of MTX. RESULTS: Toxicity-related discontinuation of MTX occurred in 38% of the placebo group, 17% of the folic acid group, and 12% of the folinic acid group. These between-group differences were explained by a decreased incidence of elevated liver enzyme levels in the folate supplementation groups. No between-group differences were found in the frequency of other adverse events or in the duration of adverse events. Parameters of disease activity improved equally in all groups. Mean dosages of MTX at the end of the study were lower in the placebo group (14.5 mg/week) than in the folic and folinic acid groups (18.0 and 16.4 mg/week, respectively). CONCLUSION: Both folate supplementation regimens reduced the incidence of elevated liver enzyme levels during MTX therapy, and as a consequence, MTX was discontinued less frequently in these patients. Folates seem to have no effect on the incidence, severity, and duration of other adverse events, including gastrointestinal and mucosal side effects. Slightly higher dosages of MTX were prescribed to obtain similar improvement in disease activity in the folate supplementation groups.

Adult↗

PubMed2001

No association between IL-10 promoter gene polymorphism and heart failure or rejection following cardiac transplantation.

Expression of interleukin (IL)-10 influences the frequency of rejection events after organ transplantation. Therefore, 70 heart transplant patients were genotyped for three single nucleotide polymorphisms and a microsatellite polymorphism in the promotor region of the IL-10 gene. The promoter region was amplified by polymerase chain reaction and genotyped by a colorometric oligo ligation assay and gene scan analysis, respectively. Patient groups consisted of patients suffering from dilated cardiomyopathy or ischaemic heart disease. Cardiac donors served as control group. No correlation was found between genotypes and heart failure or rejection after heart transplantation. This may indicate that in heart transplantation, the total balance of cytokine production is more important for post-transplant rejection activities than the levels of IL-10 as such.

Gene Expression↗

PubMed2001

Meningioma treated with interferon-alpha, evaluated with [(11)C]-L-methionine positron emission tomography.

PURPOSE: In meningioma patients with postoperative residual masses, recurrent or primarily inoperable tumors, positron emission tomography (PET) with [(11)C]-L-methionine was used to evaluate treatment efficacy of IFN-alpha. EXPERIMENTAL DESIGN: Twelve patients were treated with IFN-alpha at a dose of 1.5-5 million IU s.c. daily. PET, computed tomography, and/or magnetic resonance imaging were performed in all patients before and, at regular intervals, during IFN-alpha treatment. The ratio of tumor hot-spot uptake to cerebellar uptake or to cortex uptake was calculated. This ratio estimates the relative methionine accumulation in the tumor and presumably the proliferative activity in the tumor. RESULTS: During IFN-alpha treatment, PET demonstrated a mean relative percentage of reduction in the uptake ratio (MRelR) of 22.3% in the meningiomas. In nine patients who were considered responders, defined as patients with a positive MRelR, the MRelR was 30.4%. For the three nonresponders, defined as patients with a negative MRelR, the MRelR was -1.8%. Three patients were followed for a long time: two patients for 8 years and one patient for 4 years and 6 months; the two patients followed for 8 years are still on IFN. The volumes of these tumors were constant or showed a slight decrease. No correlation was found between histopathological diagnosis (PAD) WHO grading I-III of meningiomas and response to IFN-alpha treatment. CONCLUSIONS: PET was judged a useful method to predict which patients are suitable for long-term treatment with IFN-alpha and also for dose finding. In five patients treated from 9 months to 8 years, IFN-alpha seemed to be an effective oncostatic drug. The clinical usefulness of IFN-alpha, taking adverse reactions into account, must be evaluated in a larger series of patients.

Adult↗

PubMed2001

Accounting for age differences on the Wisconsin Card Sorting Test: decreased working memory, not inflexibility.

Two experiments examined the role of cognitive inflexibility and reduced working memory in age-related declines on the Wisconsin Card Sorting Test. Both standard scoring procedures and newly developed scores were used to measure each construct, and modifications of the test further evaluated the role of working memory. Results indicated that age differences are not due to cognitive inflexibility but that for a subset of older adults errors are associated with a reduction in the amount of information that can be stored or processed in working memory. These age differences disappear, however, when visual cues provide information about the immediately preceding sort. The authors conclude by proposing a decline in updating working memory as the explanation that can best account for the entire pattern of age differences on this test.

Adult↗

PubMed2000

Minor head injury: predicting follow-up after discharge from the Emergency Department.

BACKGROUND: Up to 50% of ED patients discharged within a minor head injury (MHI) will develop postconcussive syndrome (PCS) within 1 month of injury. The follow-up visit is an important opportunity to identify and treat PCS before it becomes persistent. OBJECTIVE: To identify factors predictive of follow-up (FU) after ED discharge in patients presenting with MHI. METHODS: Prospective, observational study of a convenience sample of 71 MHI presenting within 24 hours of injury to the ED of a university teaching hospital between February 1996 and October 1997. MHI defined as loss of consciousness not greater than 10 minutes or amnesia, GCS 15, no skull fracture on PE, no new focality to neurologic exam and no brain injury on CT if one was done. Neurobehavioural test scores, clinical information and demographic data collected via use of standardized patient encounter form. All patients were discharged with written instructions to FU with their private physician within 1-2 weeks. Patients without a follow-up physician were assigned one. At 1 month post-injury, all patients were telephoned to determine if they had followed-up. ANALYSIS: Stepwise, multivariate, logistic regression. RESULTS: Thirty one out of 71 (43.7%) reported FU with a physician within 1 month. Factors associated with FU were performance of a head CT in the ED (OR = 3.58, 95% CI = 1.12-11.37), associated laceration (OR = 8.84, 95% CI = 1.69-42.55), female gender (OR = 3.19, 95% CI = 1.04-9.82), and African-American race (OR = 0.36, 95% CI = 0.13-0.99). CONCLUSIONS: Several factors predict FU after ED discharge for MHI. Patients unlikely to FU may benefit from an assessment of PCS risk before they leave the ED.

Adolescent↗

PubMed2000

ets-2 is a target for an akt (Protein kinase B)/jun N-terminal kinase signaling pathway in macrophages of motheaten-viable mutant mice.

The transcription factor ets-2 was phosphorylated at residue threonine 72 in a colony-stimulating factor 1 (CSF-1)- and mitogen-activated protein kinase-independent manner in macrophages isolated from motheaten-viable (me-v) mice. The CSF-1 and ets-2 target genes coding for Bcl-x, urokinase plasminogen activator, and scavenger receptor were also expressed at high levels independent of CSF-1 addition to me-v cells. Akt (protein kinase B) was constitutively active in me-v macrophages, and an Akt immunoprecipitate catalyzed phosphorylation of ets-2 at threonine 72. The p54 isoform of c-jun N-terminal kinase-stress-activated kinase (JNK- SAPK) coimmunoprecipitated with Akt from me-v macrophages, and treatment of me-v cells with the specific phosphatidylinositol 3-kinase inhibitor LY294002 decreased cell survival, Akt and JNK kinase activities, ets-2 phosphorylation, and Bcl-x mRNA expression. Therefore, ets-2 is a target for phosphatidylinositol 3-kinase-Akt-JNK action, and the JNK p54 isoform is an ets-2 kinase in macrophages. Constitutive ets-2 activity may contribute to the pathology of me-v mice by increasing expression of genes like the Bcl-x gene that promote macrophage survival.

Animals↗

PubMed1999

MUC1 isoform specific monoclonal antibody 6E6/2 detects preferential expression of the novel MUC1/Y protein in breast and ovarian cancer.

The products of the MUC1 gene are known to be highly expressed in human breast cancer cells. The best characterized MUC1 protein is a polymorphic, type 1 transmembrane molecule containing a large extracellular domain composed primarily of a variable number of 20 amino acid tandem repeats. We have recently identified a novel protein product of the MUC1 gene, the MUC1/Y protein, that is also a transmembrane protein but is devoid of the tandem repeat array and its immediate flanking sequences. To analyze its expression in tumor cells we generated monoclonal antibodies directed against the MUC1/Y extracellular domain (anti-MUC1/Yex MAbs). Epitope mapping identified the MAb, 6E6, which recognized the MUC1/Y isoform with exquisite specificity- the repeat-array-containing MUC1 isoform could not compete out this immunoreactivity. A 30mer peptide which is unique for MUC1/Y and corresponds to the "join" region generated by the MUC1/Y specific splice, abrogated all 6E6 MAb immunoreactivity towards MUC1/Y. Immunoprecipitation of the MUC1/Y protein with 6E6 MAbs revealed that, in contrast with the proteolytic cleavage of the tandem-repeat-array-containing MUC1 isoform, MUC1/Y is not cleaved. Flow cytometry analyses using the 6E6 MAbs demonstrated that the MUC1/Y isoform is expressed on the cell surface of both MCF-7 breast cancer cells and malignant epithelial cells present in effusions obtained from breast and ovarian cancer patients. Our results unequivocally establish that the MUC1/Y protein is expressed on the surface of breast cancer cells and cells of other epithelial malignancies. The anti-MUC1/Y MAbs described here can target MUC1/Y expressing tumor cells in vivo and are likely to be important reagents both for epithelial tumor diagnosis and immunotherapy.

3T3 Cells↗

PubMed1998

Predictors of hospital mortality in type A aortic dissections: a retrospective analysis of 148 consecutive surgical patients.

Reports in the literature frequently concern miscellaneous types of dissections. This makes correct interpretation of data difficult. In order to assess the determinants of hospital mortality, the results of 148 consecutive patients over a 23-year period, all operated on for a type A dissection, were reviewed. Mean(s.d.) age was 56(13.1) years, 64% were male. An acute dissection (surgery within 14 days after onset of symptoms) was performed in 139 patients. Stigmata of the Marfan syndrome were present in 6.1% (n = 9). Peripheral vascular ischaemic complications were observed in 27.7%. Nowadays, diagnosis is primarily confirmed using transoesophageal echocardiography (75 correct diagnoses among 76 performed). Operation consisted of repair or replacement of the ascending aorta. Resuspension of the aortic valve was performed in 74 patients, and arch replacement in 25. In 74 patients, distal repair was done under deep hypothermic circulatory arrest. Hospital mortality rate was 23.6% (35 patients), though mortality rate calculated over the period 1990-1993 was 17.4% (P = n.s.). Univariate analysis revealed the following variables to be statistically significant predictors of hospital mortality (P < 0.05): preoperative ischaemic complications, preoperative resuscitation, haemopericardium, postoperative neurological complications, rethoracotomy, renal insufficiency and intestinal ischaemia. Multivariate stepwise logistic regression indicated preoperative resuscitation, postoperative haemodialysis and postoperative neurological complications as the only independent predictors of hospital death. Dissections arising from a primary intimal tear in the descending aorta had a more favourable outcome (P = 0.06, odds ratio 0.1). Although hospital mortality has declined over the past few years, no decline was seen in operative mortality since gelatine-resourcine-formol (GRF) glue is used as a routine. Transoesophageal echocardiography is the first choice in confirming diagnosis. Early operation is advocated, with careful haemostasis, before the development of cardiac tamponade or end-organ ischaemia, as the cornerstone of a successful treatment of a type A dissection. Reduction of neurological complications will further improve the results.

Aortic Dissection↗

PubMed1997

Somatic mutations in the human homologue of Drosophila patched in primitive neuroectodermal tumours.

The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple developmental defects and cancer susceptibility, in particular to basal cell carcinomas (BCCs). Medulloblastomas, primitive neuroectodermal tumours (PNETs) arising in childhood, occur in about 3-5% of NBCCS patients and a subset of PNETs was previously found with allelic imbalance at 9q22-q23, the region containing the gene for NBCCS (PTCH). We have analysed tumour DNA samples from 37 unrelated patients with sporadic PNETs and five medulloblastoma cell lines for PTCH mutations using an exon-by-exon single strand conformation polymorphism assay. We found three missense mutations, which affect conserved residues in transmembrane domains of the gene product and in the extracellular loop implicated in binding sonic hedgehog, one 2 bp deletion and an exon skipping splice site mutation. Most mutations were associated with the absence of the wild-type allele and were found in tumours exhibiting loss of heterozygosity (LOH) at loci flanking PTCH. The finding of LOH at 9q22-q23 in most mutated tumours while present in only three out of 26 tumours, in which a mutation was not identified, implicates PTCH as the target gene in PNETs with LOH at 9q22-q23 and deficient PTCH in the development of a subset of these tumours. Since all observed mutations were absent in the germ-line, a sporadic medulloblastoma developing as the first symptom of NBCCS is likely to be a very uncommon event.

Adolescent↗

PubMed1997

Effect of delayed intervention with ACE-inhibitor therapy on myocyte hypertrophy and growth of the cardiac interstitium in the rat model of myocardial infarction.

The effectiveness of angiotensin-converting enzyme (ACE)-inhibitor therapy in attenuating ventricular remodeling when initiated immediately following myocardial damage is clearly established. Less information, however, is available on the impact of late therapy on the remodeling process, especially its influence on the cellular components of these structural changes. The purpose of this study was to examine the effects of converting enzyme inhibitor therapy commenced 28 days following infarction in the rat on changes in cardiac myocyte dimension and the interstitium. At 28 days following infarction, myocyte cell length (153.9+/-7.3 v 131.1+/-5.9 micron, P=0.0002) and cell volume in the free wall of the left ventricle (38. 5+/-5.0 x 10(3) v31.4+/-3.1 x 10(3), P=0.009) had increased compared with sham-operated rats. Similar changes were noted in the septum and right ventricle. Captopril therapy administered between 28 and 56 days attenuated a further increase in cell length noted in an untreated group in the left ventricle (153.5+/-15.3 v 167.3+/-13.7 micron, P=0.02), right ventricle (153.8+/-20.5 v 173.8+/-2.3 micron, P=0.01) and septum (158.0+/-20.2 v 179.1+/-16.6 micron, P=0.004). There was an increase in hydroxyproline content in the right ventricle and a similar trend in the left ventricle in the untreated myocardial infarction groups. These changes were not altered by captopril therapy. In summary, even late therapy with captopril attenuates progressive myocyte remodeling, which may contribute to the ability of ACE-inhibitor therapy to slow progressive chamber enlargement following infarction.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

The effect of delayed reperfusion following infarction in the rat on structural changes in viable myocardium.

OBJECTIVE: Evidence indicates that patency of the infarct related artery following the completion of myocardial necrosis can attenuate ventricular remodeling. Data have also demonstrated that inhibition of infarct expansion contributes to the anti-remodeling effect of delayed reperfusion. However, the influence of a patent artery on components of the remodeling process in the viable myocardium is poorly understood. METHODS: Myocyte morphometrics (isolated cell technique) and collagen content (hydroxyproline analysis) were assessed 28 days following experimental myocardial infarction from rats with permanently ligated left coronary vessels (NRP; n = 10) compared with rats who underwent reperfusion 150 minutes after ligation (RP; n = 11) and a sham-operated group (n = 10). RESULTS: Analysis of infarct size (planimetry) in a separate group of rats demonstrated that reperfusion at this late time point did not reduce infarct size (NRP: 33 +/- 3 vs. RP: 35 +/- 5%). Myocyte length in RP rats was less than in NRP rats in viable, non-infarcted left ventricular tissue (155 +/- 3 vs. 167 +/- 4 microns, p = 0.02), in the right ventricle (154 +/- 4 vs. 167 +/- 3 microns, p = 0.02) and in the septum (158 +/- 4 vs. 169 +/- 4 microns, p = 0.05). Reperfusion also attenuated the expected increase in cell volume compared with NRP rats (left ventricle 39.4 +/- 1.7 x 10(3) vs. 44.1 +/- 1.6 x 10(3) micron 3, p = 0.06; right ventricle 36.7 +/- 1.6 x 10(3) vs. 42.7 +/- 2.0 x 10(3) micron 3, p = 0.02; septum 41.0 +/- 1.6 x 10(3) vs. 44.2 +/- 1.8 x 10(3) micron 3, p = 0.19). Hydroxyproline content increased in the viable left ventricular tissue in both the reperfused and non-reperfused groups. CONCLUSION: Reperfusion without myocardial salvage attenuates the increase in myocyte length and volume that occurs in remodeling myocardium following infarction in the rat, with no effect on the increase in collagen content. These data indicate that patency of the infarct vessel, which is known to have an inhibitory effect on infarct expansion, also has an anti-remodeling effect remote from the area perfused by this artery.

Animals↗

PubMed1996

Occasional memory cytotoxic T-cell responses of patients with human papillomavirus type 16-positive cervical lesions against a human leukocyte antigen-A *0201-restricted E7-encoded epitope.

Most cervical carcinoma (Cxca) cells constitutively express human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins. These proteins are, therefore, attractive targets for T cell-based immunotherapy. Previously, we identified HVP16 E7-encoded CTL epitopes. In patients with cervical intraepithelial neoplasia or Cxca, little is known concerning T-cell activity against viruses in general and against HPV16 in particular. Here, we have screened the blood of 10 healthy donor controls and of 22 patients with HPV16+ cervical lesions for the presence of CTLs directed against HPV16 E7- and control influenza virus matrix-derived epitopes presented by HLA-A *0201. We detected influenza virus-specific CTLs in all donors and in the majority of patients, indicating that most patients have functioning T-cell responses despite their lesions or therapeutic interventions. Moreover, we show that patients with HPV16+ lesions occasionally have memory CTLs against a HPV16 E7-encoded epitope (sequence YMLD-LQPETT), providing evidence for natural CTL immunity against HPV16 in patients with cervical lesions. Combined, these findings raise possibilities for vaccination with HPV16 E7-encoded peptides to induce or augment CTL responses for treatment or prevention of Cxca.

Amino Acid Sequence↗