Cellular infiltrates in the target organs associated with acute graft-versus-host disease

Acute graft-versus-host disease (AGVHD) has been one of the major obstacles in successful bone marrow transplantation for many years. The histologic manifestations of AGVHD have been well defined but much less is known about the cellular infiltrates in the target organs during AGVHD, the structure of the inflammation is different in different target organs and is not necessarily similar to classical allograft rejection. This review covers, in addition to the histologic approach, the cytologic and functional approaches to the AGVHD associated with inflammatory cells.     

Depression-executive dysfunction syndrome in stroke patients.

OBJECTIVE: It has been suggested that executive dysfunction could be the core defect in patients with geriatric or vascular depression, and that this depression-dysexecutive syndrome (DES) might be related to frontal-subcortical circuit dysfunction. The authors tested this hypothesis in 158 poststroke patients, of whom 21 had both depression and executive dysfunction. Methods: In this cross-sectional cohort study, a neurological, psychiatric, and neuropsychological examination was carried out 3 months after ischemic stroke, and brain infarcts, white-matter changes, and brain atrophy were recorded by MRI. RESULTS: The 21 patients with DES had significantly more brain infarcts affecting their frontal-subcortical circuit structures than the 137 patients without DES, or the 41 patients with depression but without executive dysfunction. Patients with DES also had more severe depressive symptoms and worse psychosocial functioning, and they coped less well in complex activities of daily living. CONCLUSIONS: DES is a valid concept and may define a subgroup of poststroke patients with frontal-subcortical pathology and with distinct prognosis and treatment options.     

A 5-year retrospective analysis of employer-provided dental care for Finnish male industrial workers

Abstract The treatment-mix, treatment time, and dental status of 268 male industrial workers entitled to employer-provided dental care were studied. The data were collected from treatment records of the covered workers over the 5-year period 1989-93. Treatment time was based on clinical treatment time recorded per patient visit, and the treatment procedure codes were reclassified into a treatment-mix according to American Dental Association categories, with a modification combining endodontics and restorative treatment. The mean number of check-ups followed by prescribed treatment (treatment courses) during the 5 years was 3.7 among those who had entered the in-house dental care program prior to the monitored period (old attenders). Their treatment time was stable, 57–63 min per year, while the first-year mean treatment time (170 min) of those who had entered the program during the study period (new attenders) was significantly higher (P<0.01) than the 5-year mean of the old attenders (61 min). Over the first 2 years, the treatment-mix of the new attenders showed a rise in diagnostic and preventive procedures from one-third to about one-half of all procedures, as it was for the old attenders. The new attenders' mean number of carious teeth (2.7), registered at the initial check-up visit, paralleled the mean recently demonstrated in the similar non-covered population. It was significantly higher than the 5-year mean of the old attenders (0.5) (P<0.001), but declined to the same level after the first year of treatment. It was concluded that the studied program seemed to contribute to a stabilization of treatment-mix, and to the establishment of a shorter annual treatment time within the first 2 years of treatment.     

Neurodynamic Studies on Emotional and Inverted Faces in an Oddball Paradigm

The detection of a change in a face stimulus was studied in an oddball paradigm. Event-related potentials (ERPs) and MEG responses to face stimuli were recorded in four conditions: 1) happy standard, neutral deviant; 2) neutral standard, neutral deviant; 3) inverted happy standard, inverted neutral deviant; 4) inverted neutral standard, inverted neutral deviant. In all conditions, the target was a face with glasses. Neutral deviants elicited a negative deflection (with a maximum around 280 ms) in ERP and MEG responses, an effect similar to auditory mismatch negativity. Face inversion diminished deviance-related negativity, implying an important role of face recognition in the observed effect. Emotional content and larger physical differences between stimuli in conditions 1 and 3 compared to conditions 2 and 4 did not show statistically significant effect on the neutral-deviant-related negativity.     

Word-specific cortical activity as revealed by the mismatch negativity

Neurophysiological brain activity evoked by individual spoken words and pseudowords was recorded and the mismatch negativity (MMN), an automatic index of experience-dependent auditory memory traces, was calculated. Consistent with earlier reported results, the MMN response to word-final syllables was enhanced compared with that elicited by the same syllables placed in a pseudoword context. Here we now demonstrate that the enhancement of the MMN elicited by two individual words showed different scalp topographies. The early word-specific brain activity is consistent with the assumption that the memory traces activated by individual words are carried by large neuronal ensembles that differ in their distributions over the cortex. Current source estimates localized the between-word differences in the right hemisphere and in parieto-occipital left-hemispheric areas. The differential brain responses to individual words appeared as early as ∼100 ms after the recognition points of the words, suggesting that their specific memory traces become active almost immediately after the information in the acoustic input is sufficient for word identification.     

Expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 (KDR/Flk-1) in ischemic skeletal muscle and its regeneration

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible endothelial cell mitogen and survival factor. Its receptor VEGFR-2 (KDR/Flk-1) mediates these effects. We studied the expression of VEGF and VEGFR-2 in ischemic human and rabbit skeletal muscle by immunohistochemistry and in situ hybridization. Human samples were obtained from eight lower limb amputations because of acute or chronic critical ischemia. In chronically ischemic human skeletal muscle VEGF and VEGFR-2 expression was restricted to atrophic and regenerating skeletal myocytes, whereas in acutely ischemic limbs VEGF and VEGFR-2 were expressed diffusely in the affected muscle. Hypoxia-inducible factor-1alpha was associated with VEGF and VEGFR-2 expression both in acute and chronic ischemia but not in regeneration. Hindlimb ischemia was induced in 20 New Zealand White rabbits by excising the femoral artery. Magnetic resonance imaging and histological sections revealed extensive ischemic damage in the thigh and leg muscles of ischemic rabbit hindlimbs with VEGF expression similar to acute human lower limb ischemia. After 1 and 3 weeks of ischemia VEGF expression was restricted to regenerating myotubes and by 6 weeks regeneration and expression of VEGF was diminished. VEGFR-2 expression was co-localized with VEGF expression in regenerating myotubes. Macrophages and an increased number of capillaries were associated with areas of ischemic muscle expressing VEGF and VEGFR-2. In conclusion, two patterns of VEGF and VEGFR-2 expression in human and rabbit ischemic skeletal muscle are demonstrated. In acute skeletal muscle ischemia VEGF and VEGFR-2 are expressed diffusely in the affected muscle. In chronic skeletal muscle ischemia and in skeletal muscle recovering from ischemia VEGF and VEGFR-2 expression are restricted to atrophic and regenerating muscle cells suggesting the operation of an autocrine pathway that may promote survival and regeneration of myocytes.     

Factors related to postmenopausal muscle performance: a cross-sectional population-based study

The aim of the present study was to investigate cross-sectionally the association of postmenopausal muscle strength with simple performance tests. A random sample of 1,166 naturally postmenopausal women (born 1932–1941) was selected from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort. Grip and quadriceps strength were measured with strain gauge dynamometers and reported in both absolute values (KPa and kg) and per kilogram of body mass (N cm^–2 kg^–1 and N kg^–1). In addition, two performance tests, ability to stand on one foot and ability to squat down to touch the floor were carried out. A five-category self-assessment of overall health (very good, good, moderate, bad, and very bad) was obtained by postal questionnaire. The women that were able to stand on one foot and able to squat down to touch the floor had greater grip and quadriceps strength than their counterparts (P<0.001 and P<0.03 in ANOVA, respectively). In addition, self-assessed health had a strong positive association with muscle strength in the grip and leg extensor muscles in ANOVA (P<0.001 between very good and moderate or poorer state of health) and regression model (P<0.001). Adjustment for age, duration of menopause, body mass, height, physical activity level, use of HRT, and number of diseases and medications did not change any of the main effects. Also, there were no differences in results between absolute measurement values and values reported per kilogram of body mass. According to the present study, a simple performance test may be useful in the prediction of postmenopausal muscle strength. Furthermore, self-assessed state of health is strongly associated with muscle strength in postmenopausal women.     

Endothelial sulfated sialyl Lewis x glycans, putative L-selectin ligands, are preferentially expressed in bronchial asthma but not in other chronic inflammatory lung diseases

Lymphocyte infiltrate is a hallmark of inflammatory responses. We have previously shown that de novo-induced endothelial sialyl Lewis x (sLex) expression guides lymphocytes in an L-selectin-dependent manner to sites of acute organ transplant rejections. In this research, we have analyzed five groups of chronic lung inflammations to determine the presence of properly glycosylated, i.e., sulfated, sLex-decorated, L-selectin ligands. Two anti-sLex (2F3 and HECA-452) and one anti-6- and/or 6'-sulfated and/or 6,6'-bisulfated (MECA-79) monoclonal antibodies (mAbs) were used. The control lung specimens did not express L-selectin ligands on endothelium. In contrast, the endothelial staining intensity and the number of positive peribronchial venules and capillaries with mAbs 2F3, HECA-452, and MECA-79 were significantly greater in bronchial biopsies from patients with asthma compared with normal specimens (P<0.003). However, no significant increase of peribronchial endothelial reactivity with these antibodies was observed in adult respiratory distress syndrome, chronic bronchitis, fibrosing alveolitis, and granulomatous inflammation compared with controls. These data suggest that sulfated sLex glycans, acting putatively as ligands for L-selectin, could be instrumental in lymphocyte extravasation into human peribronchial lung tissue during asthma, but not so important in several other inflammatory lung diseases.     

Estrogen receptor genotype modulates myocardial perfusion in young men

Most of the effects of estrogens are mediated by estrogen receptors. Vascular endothelial cells and smooth muscle cells express estrogen receptor (ESR1) in both genders. A long genotype group of a common thymine-adenine (TA) dinucleotide repeat polymorphism in the regulatory region of this gene has previously been related to coronary artery disease. The present study examined whether coronary blood flow is affected by this genotype. A total of 49 healthy men were genotyped by PCR and divided into three groups according to median number of the ESR1 promoter TA repeat (=19), i.e., in the short allele genotype group both alleles were of fewer than 19 repeats whereas in the long allele group both alleles were 19 repeats or more. The intermediate group comprised men who had one short and one long allele. Myocardial blood flow was measured by positron emission tomography using [¹⁵O]water, performed at rest and during adenosine stimulation. Men with long alleles had lower adenosine-stimulated coronary flow than those with short alleles and those with one short and one long allelle. Our results suggest that adenosine-stimulated myocardial perfusion is lower in subjects with ESR1 long alleles than the other TA repeat genotypes.