Cat-301 immunoreactivity in the lateral geniculate nucleus and visual cortex of the strabismic amblyopic cat

Purpose: It was investigated whether alterations in neuronal structure and function occasioned by strabismic amblyopia also may be reflected in alterations in the expression on Y type neurons of a Cat-301 antibody sensitive antigen in the lateral geniculate nucleus (LGN) and cortex of our cat model of strabismic amblyopia. Methods/Results: The percentage of positively labelled cells was reduced in LGN laminae that received input from the deviated eye in strabismic amblyopic cats compared with normal cats. In the strabismic cortex, the density of immunopositive neurons was significantly reduced compared with normal, the effect being most pronounced in layer IV Conclusions: Despite previous physiological recordings indicating a decrease in X-cell associated acuity in strabismic amblyopia, the present findings imply that the changes in the early visual experience occasioned by strabismus also produce specific molecular changes in theY neuronal class.     

Decreased expression of DMPK: correlation with CTG repeat expansion and fibre type composition in myotonic dystrophy type 1

Abstract Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a trinucleotide repeatexpansion, cytosine-thymine-guanine (CTG)_n, in the 3′ untranslated region of a gene encoding the myotonic dystrophy protein kinase (DMPK). To correlate CTG expansion and protein expression, we studied muscle specimens from 16 adult DM1 patients using three anti-DMPK antibodies for immunoblotting. We estimated the amount of the full-length DMPK (85 kDa) in muscle biopsies from normal controls and from DM1 patients carrying different (CTG)_n expansions. We found that DMPK concentration was decreased to about 50% in DM patients’ muscles; the protein decrease did not seem correlated with the CTG repeat length. However, the fibre type composition in skeletal muscle seemed somehow to affect DMPK decrease, as the lowest level of the enzyme was found in patients with the lowest content of type 1 fibre.     

Evacuation of hematomas using liposuction technology: Technique and literature review

Established nonexpanding hematomas can be successfully treated with minimal morbidity using standard liposucstion techniques at the bedside or in an outpatient setting under local anesthesia. The authors presents a series of eight patients and discuss current concepts of dealing with this common and distressing surgical complication.     

Zur Zulässigkeit des Verzichts auf Zuzahlungen durch eine Krankenkasse im Rahmen integrierter Versorgung

Ohne Zusammenfassung     

Serum selenium and coronary heart disease risk factors in southern Italian men.

The association between serum selenium concentration and a number of coronary heart disease risk factors is studied in 364 males from southern Italy participating in the Olivetti Heart Study. Selenium correlates positively and significantly with serum cholesterol (r = 0.120; P = 0.022), and this positive association persists after adjustment for age and body mass index. Selenium levels in heavy smokers are lower than both light smokers and current non-smokers, but these differences do not reach statistical significance. Selenium is not significantly associated with any of the other CHD risk factors (e.g., triglycerides, HDL cholesterol, blood pressure, age, and body mass index). It is hypothesized that the association between selenium and serum cholesterol reported in this and previous studies could be due to dietary interrelationships between selenium intake and foods that affect serum cholesterol concentrations.     

Intracellular pH and Na+/H+ antiport activity of cultured skin fibroblasts from diabetics.

Increased leucocyte Na+/H+ antiport activity has previously been demonstrated in both hypertensive subjects and Type 1 diabetic patients with nephropathy and may indicate a predisposition to hypertension in such diabetic patients. We have studied intracellular pH and Na+/H+ antiport activity in cultured skin fibroblasts from diabetic patients with and without nephropathy, together with non-diabetic controls to assess if such differences persisted in cultured cells. Fibroblasts from diabetic patients with nephropathy were significantly more alkaline [median (range): 6.90 (6.82 to 7.07)] compared to both normoalbuminuric diabetic patients [6.81 (6.75 to 6.89)] or normal controls [6.82 (6.77 to 6.93)] (P < 0.001 for both). This was associated with a raised Na+/H+ antiport activity in cells from patients with nephropathy when intracellular pH (pHi) was clamped to pH 6.5, without any differences in the maximal transport capacity of the antiport at pHi 6.2. Using both intracellular pH and Na+/H+ antiport activity at pHi 6.5, patients with nephropathy were separated from uncomplicated subjects with a sensitivity of 92% and a specificity of 100%. In conclusion, the raised Na+/H+ antiport activity in cells from patients with diabetic nephropathy persists despite passaging in vitro, thus indicating a heritable component, and results mainly from an increased apparent affinity of the antiport for intracellular H+.     

Biochemical actions of chronic ethanol exposure in the mesolimbic dopamine system

In previous studies, we have demonstrated that chronic administration of morphine or cocaine produces some common biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc), components of the mesolimbic dopamine system implicated in the reinforcing actions of these and other drugs of abuse. Since this neural pathway is also implicated in the reinforcing actions of ethanol, it was of interest to determine whether chronic ethanol exposure results in similar biochemical adaptations. Indeed, as seen for chronic morphine and cocaine treatments, we show here that chronic ethanol treatment increased levels of tyrosine hydroxylase and glial fibrillary acidic protein immunoreactivity, and decreases levels of neurofilament protein immunoreactivity, in the VTA. Also like morphine and cocaine, ethanol increases levels of cyclic AMP-dependent protein kinase activity in the NAc. These actions of ethanol required long-term exposure to the drug, and were in most cases not seen in the substantia nigra or caudate-putamen, components of the nigrostriatal dopamine system studied for comparison. Altered levels of tyrosine hydroxylase in catecholaminergic cells frequently reflect altered states of activation of the cells. Moreover, increasing evidence indicates that ethanol produces many of its acute effects on the brain by regulating NMDA glutamate and GAB_A receptors. We therefore examined the influence of chronic ethanol treatment on levels of expression of specific glutamate and GABA receptor subunits in the VTA. It was found that long-term, but not short-term, ethanol exposure increased levels of immunoreactivity of the NMDARl subunit, an obligatory component of NMDA glutamate receptors, and of the Glu Rl subunit, a component of many AMPA glutamate receptors; but at the same time, long-term ethanol exposure decreased immunoreactivity levels of the α1 subunit of the GABA_A receptor complex. These changes are consistent with an increased state of activation of VTA neurons inferred from the observed increase intyrosine hydroxylase (TH) expression. These results demonstrate that chronic ethanol exposure results in several biochemical adaptations in the mesolimbic dopamine system, which may underlie prominent changes in the structural and functional properties of this neural pathway related to alcohol abuse and alcoholism. © 1995 Wiley-Liss, Inc.     

Clinical and molecular study in congenital muscular dystrophy with partial laminin alpha 2 (LAMA2) deficiency

Complete laminin alpha2 (LAMA2) deficiency causes approximately half of congenital muscular dystrophy (CMD) cases. Many loss-of-function mutations have been reported in these severe, neonatal-onset patients, but only single missense mutations have been found in milder CMD with partial laminin alpha2 deficiency. Here, we studied nine patients diagnosed with CMD who showed abnormal white-matter signal at brain MRI and partial deficiency of laminin alpha2 on immunofluorescence of muscle biopsy. We screened the entire 9.5 kb laminin alpha2 mRNA from patient muscle biopsy by direct capillary automated sequencing, single strand conformational polymorphism (SSCP), or denaturing high performance liquid chromatography (DHPLC) of overlapping RT-PCR products followed by direct sequencing of heteroduplexes. We identified laminin alpha2 sequence changes in six of nine CMD patients. Each of the gene changes identified, except one, was novel, including three missense changes and two splice-site mutations. The finding of partial laminin alpha2 deficiency by immunostaining is not specific for laminin alpha2 gene mutation carriers, with only two patients (22%) showing clear causative mutations, and an additional three patients (33%) showing possible mutations. The clinical presentation and disease progression was homogeneous in the laminin alpha2-mutation positive and negative CMD patients.     

Alteration of the follicular basement membrane in non-obese diabetic mice with spontaneous autoimmune thyroiditis

The follicular basement membrane (FBM) prevents thyroglobulin from escaping to the peri-follicular space, where it can act as an antigen to induce experimental thyroiditis. Laminin, a component of the FBM, is responsible for directing cell migration and stimulates greater adhesion of activated T lymphocytes. Our purpose was to study the expression of laminin in the thyroid of NOD mice, which have a propensity for autoimmune diseases, including thyroiditis. Thirty NOD mice between 3 and 42 weeks old were studied. Eight had thyroiditis and 22 showed no inflammatory infiltration. An immunohistochemical examination using the streptavidin-biotin-peroxidase technique was conducted on paraffin-embedded tissue sections, with a polyclonal antilaminin antibody. Antigen retrieval was achieved through pepsin digestion and microwave irradiation in citrate buffer. Staining for laminin was restricted to the basement membrane. In thyroids with no infiltration, laminin was shown as a fine, continuous brown line in the basement membrane. In 6 out of the 8 cases of thyroiditis, clearcut interruption and destruction of the FBM was observed, particularly when the follicles were located in lymphocyte infiltrated areas or when there was fibrosis. There were significant alterations in the pattern of the FBM with extensive areas of discontinuity in the distribution of laminin. Such discontinuities could facilitate antigen exposure, especially thyroglobulin, which may contribute to autoimmune thyroiditis in NOD mice.