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Biomedical subjects

H Kalimo

Publications and source records attributed to H Kalimo.

At least 19 recordsLinked to original sources
PubMed2006

Skeletal muscle HSP expression in response to immobilization and remobilization.

Heat shock proteins play an important regulatory role in the cellular defence. Oxidative stress is one of the factors inducing heat shock protein expression. This study tested the effects of 4 weeks of immobilization and subsequent remobilization on heat shock protein expression and oxidative stress in the lateral gastrocnemius and plantaris muscles of the rat. Active mobilization or free mobilization protocols were used for remobilization. In active mobilization, strenuous uphill treadmill running, twice a day, was started immediately after the immobilization and lasted for six days. Rats in the free mobilization group moved freely in their cages immediately after the immobilization. Expression of heat shock proteins was upregulated during the recovery from immobilization, especially in the lateral gastrocnemius muscle in the active mobilization group. However, markers of oxidative stress, such as protein carbonyls and 4-hydroxynonenal protein adducts, or activities of the antioxidant enzymes glutathione peroxidase and glutathione reductase, did not change after the immobilization and subsequent recovery. In summary, following immobilization, both intensive and spontaneous exercise upregulated the heat shock protein expressions in the lateral gastrocnemius muscle and partly in the plantaris muscle, which may contribute to the recovery from immobilization atrophy.

Animals↗
PubMed2006

Neurophysiological and mitochondrial abnormalities in MuSK antibody seropositive myasthenia gravis compared to other immunological subtypes.

OBJECTIVE: To compare the electrophysiological and histopathological features of immunological myasthenia gravis (MG) subtypes. METHODS: Fifty MG patients underwent clinical examination, MuSK-Ab and AChR-Ab analysis. The majority underwent quantitative and single-fiber electromyography (QEMG, SFEMG), repetitive nerve stimulation and deltoid muscle biopsy. From muscle specimens with histological mitochondrial dysfunction, we amplified mitochondrial DNA (mtDNA). In specimens with mtDNA deletions, the nuclear gene POLG1 was sequenced. RESULTS: Five AChR-Ab seropositive [AChR(+)] and 5 seronegative [AChR(-)] patients were MuSK-Ab seropositive [MuSK(+)]. Five of 7 neurophysiologically examined MuSK(+) patients (71%) had proximal myopathic pattern, compared to 7 of 31 MuSK(-)/AChR(+) patients (23%) (P=0.012). SFEMG was abnormal in all examined MuSK(+) patients. All 7 biopsied MuSK(+) and 32 MuSK(-) patients (89%) had cytochrome c oxidase (COX) negative fibers. Three of five MuSK(+) and 13 of 20 MuSK(-) patients analyzed had multiple mtDNA deletions but no POLG1 mutations. CONCLUSIONS: Similar degree of SFEMG abnormalities was present in proximal muscles among MuSK(+) and AChR(+) patients. Proximal myopathy was over-represented in MuSK(+) patients; however, both MuSK(+) and MuSK(-) patients had mild myopathy with frequent mitochondrial abnormalities. SIGNIFICANCE: The weakness in MuSK(+) patients is most likely due to disturbed neuromuscular transmission. The frequently encountered mitochondrial dysfunction in MG warrants further study.

Action Potentials↗
PubMed2006

MR characteristics and neuropathology in adult-onset autosomal dominant leukodystrophy with autonomic symptoms.

BACKGROUND AND PURPOSE: Three families with adult-onset autosomal dominant leukodystrophy (ADLD) presenting autonomic dysfunction as the first symptom are reported. We describe detailed MR appearances of the brain in 2 new families and neuropathology in 2 patients and compare the findings with those in other adult-onset leukodystrophies. METHODS: Twenty subjects (12 women and 8 men; age range, 29-70 years) from 2 unrelated families with ADLD were examined with MR. Six subjects were asymptomatic. Fourteen had autonomic dysfunction. Eleven of them also had pyramidal signs and ataxia. The brains of 2 autopsied patients were examined histopathologically. RESULTS: Two subjects manifested no neurologic symptoms, signs, or MR pathology. Eighteen subjects displayed radiologic abnormalities ranging from subtle T2 high-signal-intensity changes in the upper corticospinal tract to extensive confluent white matter changes, predominantly in a frontoparietal distribution, along the corticospinal tracts down to the medulla oblongata and in the upper and middle cerebellar peduncles. Periventricular white matter was spared or less affected than the adjacent white matter. Histopathology revealed marked loss of cerebral and cerebellar myelin without signs of inflammation. Oligodendrocytes were relatively spared, the number of axons not markedly decreased, and reactive gliosis was modest. The number of Purkinje cells in the cerebellum was reduced. CONCLUSIONS: Two families with adult-onset ADLD with the disease entity originally reported by Eldridge et al. (N Engl J Med 1984;311:948-53) were described. We propose naming the disease "adult-onset ADLD with autonomic symptoms." The characteristic radiologic findings, combined with the clinical symptoms and mode of inheritance, enable the diagnosis.

Adult↗
PubMed2005

Similar brain tau pathology in DM2/PROMM and DM1/Steinert disease.

Neurofibrillary degeneration (NFD) occurs in the brains of patients with myotonic dystrophy (DM) type 1. The authors report a similar tau pathology in the CNS of a patient with DM2 and compare it to that of patients with DM1. A reduced expression of tau exon 2 and exon 3 epitopes is observed in both DM1 and DM2. This suggests a similar physiopathologic process that may contribute to common neurologic features in patients with DM.

Aged↗
PubMed2005

Neurologic symptoms are common during gestation and puerperium in CADASIL.

Based on a structured questionnaire and medical records, the authors found that 12 of 25 mothers with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with the R133C NOTCH3 mutation had had neurologic symptoms in 17 of their 43 pregnancies, most commonly hemiparesthesia (76%), hemiparesis (36%), aphasia (65%), and visual disorders (47%). In 82% of the patients, the symptoms were the first manifestation of CADASIL. The symptoms were most common during puerperium and in patients older than age 30.

Adult↗
PubMed2005

Enrichment of the R77C alpha-sarcoglycan gene mutation in Finnish LGMD2D patients.

Limb-girdle muscular dystrophy 2D (LGMD2D) is caused by mutations in the alpha-sarcoglycan gene (SGCA). The most frequently reported mutation, 229CGC>TGC (R77C) in exon 3 of SGCA, results in the substitution of arginine by cysteine. We present here the clinical, immunohistochemical, and genetic data of 11 Finnish patients with LGMD2D caused by mutations in SGCA. Mutational analysis showed 10 patients homozygous and 1 compound heterozygous for R77C. A wide spectrum of SGCA mutations has been reported previously. Our results show an enrichment of R77C in Finland, further underlined by the observed carrier frequency of 1 per 150. According to the annual birth rate of approximately 60,000 in Finland, one LGMD2D patient with a homozygous mutation is expected to be born every 1 or 2 years on average. The presence of an ancient founder mutation is indicated by the fact that all patients shared a short common haplotype extending > or = 790 kilobases. Our results emphasize the need to include the SGCA gene R77C mutation test in routine DNA analyses of severe dystrophinopathy-like muscular dystrophies in Finland, and suggest that the applicability of this test in other populations should be studied as well.

Adolescent↗
PubMed2004

Non-traumatic forensic neuropathology.

The practicing Forensic Pathologist is likely to encounter case material in which either the cause of death or a major contribution to the cause of death is underlying damage to or disease of the central nervous system. While it is good practice in many instances to have a working relationship with a Department of Neuropathology, from which advice and practical help can be sought, there may be instances when the Forensic Pathologist needs to proceed on a basis of a working knowledge of Forensic Neuropathology up to and including how to examine the specimen and take tissue blocks for processing and subsequent histological examination. Some of the more common conditions of the central nervous system such as damage consequent to hypoxia-ischaemia, hypoglycemia and epilepsy, the encephalopathies associated with altered sodium concentration, deficiency due to Vitamin B(1) and various neurodegenerative diseases that manifest as dementia and include Alzheimer's disease, cortical Lewy body disease and the prion disorders, are outlined in this article.

Brain↗
PubMed2004

The pathogenesis of CADASIL: an update.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) appears to be the most common form of hereditary stroke disorder. CADASIL is associated with arterial smooth muscle degeneration linked to mutations in the Notch3 gene, whose product is a transmembrane receptor that functions in cell-cell communication. The pathogenesis of CADASIL remains unclear. Current research efforts are directed towards the elucidation of various features of the disorder including investigations on CADASIL-like disorders, early cognitive changes, specificity of neuroimaging for diagnosis, discovery of de novo mutations, the development of Notch3 transgenic mouse models and molecular cellular studies in Notch3 signaling. The genetics of cerebrovascular disorders (CVD) was virtually unknown until recently. Genetic associations may have been evaded because of widely variable phenotypes, even within monogenic disorders such as CADASIL. Several investigators have attempted genotype-phenotype correlation in CADASIL cases but the relationship between genetic alterations and overt manifestation of phenotype remains elusive. However, the elucidation of the genetics and pathogenesis of CADASIL have been important in further understanding of the primary vascular mechanisms that lead to ischemic blood flow and its consequences on neuronal survival. This report summarizes some of the highlights of the satellite symposium on CADASIL at Vas-Cog 2003.

Animals↗
PubMed2004

New methods for molecular diagnosis and demonstration of the (CCTG)n mutation in myotonic dystrophy type 2 (DM2).

Myotonic dystrophy types 1 and 2 are autosomal dominant, multisystemic disorders with many similarities in their clinical manifestations. Myotonic dystrophy type 1 is caused by a (CTG)n expansion in the 3' untranslated region of the DMPK gene in 19q13.3 and myotonic dystrophy type 2 by a (CCTG)n expansion in intron 1 of ZNF9 in 3q21.3. However, the clinical diagnosis of myotonic dystrophy type 2 is more complex than that of myotonic dystrophy type 1, and conventional molecular genetic methods used for diagnosing myotonic dystrophy type 1 are insufficient for myotonic dystrophy type 2. Herein we describe two in situ hybridization protocols for the myotonic dystrophy type 2 mutation detection. Chromogenic in situ hybridization was used to detect both the genomic expansion and the mutant transcripts in muscle biopsy sections. Chromogenic in situ hybridization can be used in routine myotonic dystrophy type 2 diagnostics. Fluorescence in situ hybridization on extended DNA fibers was used to directly visualize the myotonic dystrophy type 2 mutation and to estimate the repeat expansion sizes.

Adult↗
PubMed2004

Mast cells and IgE-containing cells in gastric mucosa of Helicobacter pylori infected and non-infected patients with chronic urticaria.

BACKGROUND: Several studies have indicated that antibiotic therapy aimed at eradication of Helicobacter pylori has effects on symptoms of chronic urticaria (CU) patients. However, the possible connections and pathomechanism by which H. pylori might be linked to CU have remained largely unknown. The IgE-mediated pathway might be a possible link between H. pylori infection and CU. We therefore clarified the role of H. pylori as an inducer of IgE response. MATERIALS AND METHODS: Gastroscopy was performed and mucosal biopsy specimens were taken to evaluate the histology, as well as the presence of H. pylori bacteria, mast cells and IgE-containing cells in the antral mucosa, in 21 CU patients. Controls (n = 48) included 19 patients with lichen planus, nine patients with atopic dermatitis and 20 patients with no skin or allergic disease. RESULTS: The mean densities of IgE-containing cells were significantly higher in H. pylori-infected patients and in patients with skin disease compared to non-H. pylori-infected patients with no skin or allergic disease. No significant difference was found in the number of IgE-containing cells between H. pylori-infected and non-infected patients with CU. There was no significant difference in the mean densities of mast cells in the different patient groups. CONCLUSIONS: Our findings suggest that H. pylori gastritis leads to increased IgE production. However, we could not show a significant difference in IgE staining between H. pylori-infected and non-infected patients with CU.

Adult↗
PubMed2003

Evaluation of brain tumor metabolism with [11C]choline PET and 1H-MRS.

BACKGROUND: The signal of choline containing compounds (Cho) in proton magnetic resonance spectroscopy (1H-MRS) is elevated in brain tumors. [11C]choline uptake as assessed using positron emission tomography (PET) has also been suggested to be higher in brain tumors than in the normal brain. We examined whether quantitative analysis of choline accumulation and content using these two novel techniques would be helpful in non-invasive, preoperative evaluation of suspected brain tumors and tumor malignancy grade. METHODS: 12 patients with suspected brain tumor were studied using [11C]choline PET, gadolinium enhanced 3-D magnetic resonance imaging and 1H-MRS prior to diagnostic biopsy or resection. Eleven normal subjects served as control subjects for 1H-MRS. RESULTS: The concentrations of Cho and myoinositol (mI) were higher and the concentration of N-acetyl signal/group (NA) lower in brain tumors than in the corresponding regions of the normal brain. There were no significant differences in metabolite concentrations between low- and high-grade gliomas. In non-tumorous lesions Cho concentrations were lower and NA concentrations higher than in any of the gliomas. Enormously increased lipid peak differentiated lymphomas from all other lesions. The uptake of [11C]choline at PET did not differ between low- and high-grade gliomas. The association between Cho concentration determined in 1H-MRS and [11C]choline uptake measured with PET was not significant. CONCLUSION: Both 1H-MRS and [11C]choline PET can be used to estimate proliferative activity of human brain tumors. These methods seem to be helpful in differential diagnosis between lymphomas, non-tumorous lesions and gliomas but are not superior to histopathological methods in estimation of tumor malignancy grade.

Adult↗
PubMed2002

Narrowing in on the causative defect of an intriguing X-linked myopathy with excessive autophagy.

BACKGROUND: X-Linked myopathy with excessive autophagy (XMEA) is a childhood-onset slowly progressive disease of skeletal muscle with no cardiac, nervous system, or other organ involvement. Pathology is distinctive: membrane-bound autophagic vacuoles, multifold reduplication of the basement membrane, and intense deposition of membrane attack complex and calcium at the myofiber surface. XMEA has been linked to the most telomeric 10.5 cM of Xq28. The authors now report identification of new families, refinement of the locus, mapping of genes to the region, and screening of candidate genes for mutations. METHODS AND RESULTS: Seven new families were ascertained, including an American family with XMEA. Using 11 new microsatellite genetic markers, the authors fine-mapped a recombination in this family and a common ancestral haplotype in two French families, which localized the gene in a 4.37-Mb region. Sequence data were assembled from public and private databases and a near-continuous sequence derived for the entire region. With this sequence, a gene map of 82 genes and 28 expressed sequence tag clusters was constructed; to date, 12 candidate genes have been screened for mutations. CONCLUSIONS: This study doubles the number of reported families with XMEA and more firmly establishes its distinctive clinicopathologic features. It also advances the search for the XMEA causative defect by reducing the disease locus to approximately half its previous size, assembling an almost complete sequence of the refined region, identifying all known genes in this sequence, and excluding the presence of mutations in 10% of these genes.

Adolescent↗
PubMed2002

The histaminergic system in human thalamus: correlation of innervation to receptor expression.

The mRNA expression of three histamine receptors (H1, H2 and H3) and H1 and H3 receptor binding were mapped and quantified in normal human thalamus by in situ hybridization and receptor binding autoradiography, respectively. Immunohistochemistry was applied to study the distribution of histaminergic fibres and terminals in the normal human thalamus. mRNAs for all three histamine receptors were detected mainly in the dorsal thalamus, but the expression intensities were different. Briefly, H1 and H3 receptor mRNAs were relatively enriched in the anterior, medial, and part of the lateral nuclei regions; whereas the expression level was much lower in the ventral and posterior parts of the thalamus, and the reticular nucleus. H2 receptor mRNA displayed in general very low expression intensity with slightly higher expression level in the anterior and lateropolar regions. H1 receptor binding was mainly detected in the mediodorsal, ventroposterolateral nuclei, and the pulvinar. H3 receptor binding was detected mainly in the dorsal thalamus, predominantly the periventricular, mediodorsal, and posterior regions. Very high or high histaminergic fibre densities were observed in the midline nuclear region and other nuclei next to the third ventricle, ventroposterior lateral nucleus and medial geniculate nucleus. In most of the core structures of the thalamus, the fibre density was very low or absent. The results suggest that histamine in human brain regulates tactile and proprioceptory thalamocortical functions through multiple receptors. Also, other, e.g. visual areas and those not making cortical connections expressed histamine receptors and contained histaminergic nerve fibres.

Adult↗
PubMed2002

Increased brain histamine levels in Parkinson's disease but not in multiple system atrophy.

We investigated histamine concentration in post-mortem brain samples of patients with Parkinson's disease (PD, n = 24), multiple system atrophy (MSA, n = 8) and age-matched controls (n = 27). Histamine concentrations were significantly increased in the putamen (to 159% of the control mean), substantia nigra pars compacta (to 201%), internal globus pallidus (to 234%) and external globus pallidus (to 200%), i.e. in areas which play a crucial role in the motor behaviour and which show typical functional alterations in PD. In MSA no significant differences were seen. Tele-methylhistamine (histamine metabolite) concentrations were unchanged in PD. These results indicate that histamine concentration, but not its metabolism is increased in PD, but not in MSA. This finding may have implications in developing new drug therapies for PD and in differential diagnosis between PD and MSA.

Aged↗
PubMed2001

Distribution and modulation of histamine H(3) receptors in basal ganglia and frontal cortex of healthy controls and patients with Parkinson's disease.

Parkinson's disease (PD) is a brain degenerative disorder with unknown etiology, and specific degeneration of mesencephalic dopaminergic cells is a morphological manifestation of the disease. The central histaminergic system appears to be activated in PD, since the histaminergic innervation is increased in the substantia nigra. The aim of the present study was to investigate the expression and function of histamine H(3) receptors in PD, using receptor mRNA in situ hybridization with oligonucleotide probes, receptor binding assay with a specific radioactive agonist, and GTP-gamma-[(35)S]-binding assay as a tool to study the activation of the receptor G-protein. H(3) receptor binding sites were detected using N-alpha-methylhistamine autoradiography in the basal ganglia and cortex, being most abundant in the substantia nigra and striatum. In PD substantia nigra we detected an increase of the receptor binding density. In situ hybridization study of the receptor mRNA revealed prominent sites of H(3) receptor synthesis in the putamen, cortex, and globus pallidus, whereas very low mRNA expression was seen in the substantia nigra. In the PD pallidum externum, H(3) receptor mRNA expression was elevated as compared with the normal brains. GTP-gamma-[(35)S]-binding assay did not reveal any significant difference between PD and normal brains, although the density values in PD substantia nigra tended to be lower than in the normal brain, and density values in PD striatum were higher. The dopaminergic neurons did not express significant amount of H(3) receptor mRNA, suggesting that the effects of H(3) receptor-mediated modulation of dopamine release are indirect. Our data indicates modulation of the histamine H(3) receptor in PD at the level of the mRNA expression in the striatum and receptor density in the substantia nigra. The receptor activity seems to be unchanged or decreased, as revealed by GTP-gamma-[(35)S]-binding assay. Modulation of the histamine H(3) receptor may influence the activity of other neurotransmitter systems, e.g., the GABAergic one, in the substantia nigra.

Aged↗
PubMed2001

Regulation of alpha7 integrin by mechanical stress during skeletal muscle regeneration.

The continuity of the tendon-myofibre-tendon units disrupted by shearing injury must be re-established during regeneration. We have previously demonstrated in freely moving rats that transected myofibres reinforce their lateral integrin-mediated adhesion, with the maximum around days 5-7. After day 14, most integrin molecules are redistributed to the newly formed myotendinous junctions, by which the ends of regenerating myofibres attach to the scar between the stumps. Here, we analyzed the effects of mechanical stress (free and forced mobilization vs. immobilization and denervation separately and in combination) on the expression of alpha7 integrin and merosin in regenerating myofibres using quantitative in situ hybridization and immunohistochemistry. In all groups, alpha7 integrin expression was upregulated at mRNA level, whereas increased protein accumulation in lateral sarcolemma occurred only in the mobilized groups. The accumulation of merosin was not affected by the stress level. The results demonstrate that active mechanical stress reinforces early lateral integrin-mediated adhesion; molecules may at the same time mediate signals from matrix to cells for adaptation to the altered biomechanical status.

Animals↗