Structural Changes Associated with Progression of Motor Deficits in Spinocerebellar Ataxia 17

Spinocerebellar ataxia (SCA17) is a rare genetic disorder characterized by a variety of neuropsychiatric symptoms. Recently, using magnetic resonance imaging (MRI) voxel-based morphometry (VBM), several specific functional–structural correlations comprising differential degeneration related to motor and psychiatric symptoms were reported in patients with SCA17. To investigate gray matter volume (GMV) changes over time and its association to clinical neuropsychiatric symptomatology, nine SCA17 mutation carriers and nine matched healthy individuals underwent a detailed neuropsychiatric clinical examination and a high-resolution T1-weighted volume MRI scan, both at baseline and follow-up after 18 months. Follow-up images revealed a progressive GMV reduction in specific degeneration patterns. In contrast to healthy controls, SCA17 patients showed a greater atrophy not only in cerebellar regions but also in cortical structures such as the limbic system (parahippocampus, cingulate) and parietal precuneus. Clinically, progression of motor symptoms was more pronounced than that of psychiatric symptoms. Correlation with the clinical motor scores revealed a progressive reduction of GMV in cerebellar and cerebral motor networks, whereas correlation with psychiatric scores displayed a more widespread GMV impairment in frontal, limbic, parietal, and also cerebellar structures. Interestingly, changes in global functioning were correlated with bilateral atrophy within the para-/hippocampus. While there was a good temporal association between worsening of motor symptoms and progression in cerebral and cortical neurodegeneration, the progression in psychiatric related neurodegeneration seemed to be more widespread and complex, showing progressive atrophy that preceded the further development of clinical psychiatric symptoms.     

Isolation of Babesia microti (Fran?a 1912) from free-living nymphs of Ixodes ricinus (Linnaeus 1758) (author's transl)

375 unfed nymphs of Ixodes ricinus were collected in a natural focus of Babesia microti near Hannover and were tested for an infection with B. microti using golden hamsters (Mesocricetus auratus). 2 strains (Hannover II and Hannover III) were isolated. The incidence of infected nymphs in April 1980 demonstrates the ability of B. microti to hibernate in I. ricinus under natural conditions.     

Right ventricular ejection fraction and volumes after mustard repair: Correlation of two dimensional echocardiograms and cineangiograms

The right ventricular ejection fractions derived from two dimensional echocardiograms and cineangiograms were compared in 24 children. All patients (aged 2.1 to 16 years) had undergone Mustard repair for transposition of the great arteries 1 to 12 years earlier. The correlation of the two methods was excellent (r = 0.977), confirming the usefulness of echocardlography for deriving ejection fraction. The volume components of the ejection fraction were less well estimated from the echocardiograms, but the ratios of end-diastolic to end-systolic volumes estimated from each method were similar.     

Nosocomial infection of the urinary tract

Urinary tract infections appear to be responsible for 35 percent of all hospital-acquired infections, occurring in approximately two patients per 100 admissions. The great majority of infections are associated with urinary tract instrumentation. Female sex, advanced age and debilitating underlying illness appear to be associated with an increased risk of infection, but other risk factors have been poorly defined and case-control studies assessing excess morbidity and mortality associated with nosocomial bacteriuria have not been made. In most instances, the hospitalized patients are the reservoirs for the etiologic organisms, but cross infection from other infected patients also occurs. Current preventive efforts have been primarily directed at aseptic catheter care techniques and reducing catheter use. Further developments in our prevention and control of these infections require an understanding of the mechanisms responsible for colonization of the urethra and bladder with gram-negative organisms and ways to discriminate patients at especial risk.     

The effect of continuous normalization of serum hemolytic complement on the course of lupus nephritis: A five year prospective study

We have completed a five year prospective study of the effect of continuous normalization of serum hemolytic complement (CH₅₀) in 25 patients with lupus nephritis. At the end of five years 22 patients were being actively followed; 13 in a CH₅₀ controlled group and nine in a CH₅₀ uncontrolled group. Serial renal biopsy specimens were obtained from 19 patients. The results demonstrate a trend toward stabilization of renal histology, creatinine clearance and serum creatinine at a lower final mean dose of prednisone in the complement controlled group.     

Plasma apolipoprotein concentrations in familial apolipoprotein A-I and A-II deficiency (Tangier disease)

Familial apolipoprotein A-I and A-II deficiency (Tangier disease) is characterized by cholesterol ester deposition in histiocytes, decreased plasma cholesterol and low density lipoprotein cholesterol (C-LDL), and a striking deficiency of high density lipoproteins (HDL). We measured plasma lipid, lipoprotein cholesterol, and plasma apolipoprotein (apo) A-I, A-II, B, C-I, C-II, C-III, D, and E concentrations in 7 Tangier homozygotes, 2 obligate heterozygotes, and 50 normal subjects. Heterozygotes had modest reductions in high density lipoprotein cholesterol (C-HDL), plasma apoA-I, and apoA-II levels. Mean concentrations (±SD) of plasma C-HDL and apolipoproteins A-I, A-II, B, C-I, C-II, C-III, D, and E in mg% in normals were: 50 ± 14, 134 ± 24, 68 ± 18, 98 ± 20, 7 ± 2, 3.7 ± 2, 13 ± 5, 10 ± 4, and 10 ± 4, respectively; and in homozygotes were: 1 ± 1, 1.3 ± 0.7, 4.8 ± 2.5, 82.6 ± 18, 4.1 ± 1.7, 2.3 ± 0.9, 6.5 ± 3.8, 2.2 ± 0.5, and 5.4 ± 3.1, respectively. Homozygotes had C-HDL, apoA-I and apoA-II levels which were 2%, 1%, and 7% (p < .001) of normal, respectively, and mean levels of apolipoproteins B, C-I, C-II, C-III, D, and E which were 84%, 59%, 62%, 50%, 22%, and 54% of normal, respectively. There was heterogeneity of these latter apolipoprotein concentrations among homozygotes. Mean apoC-I, apoC-III, apoD, and apoE levels were significantly less than normal (pp < .05) in homozygotes. These data indicate that homozygotes have variable but generally decreased apoC and apoE levels, a deficiency of apoD, and a striking reduction in plasma apoA-I and apoA-II concentrations.     

Solution conformation of gramicidin S: An intramolecular nuclear Overhauser effect study

The solution conformation of gramicidin S in deuterated dimethyl sulfoxide was investigated by using the intramolecular nuclear Overhauser effect experiment. Experimental Overhauser enhancements were compared with predicted values for each of the nine most-stable conformations (M1-M9) calculated by Dygert et al. on the basis of energy-minimization procedures [Dygert, M., Gō, N. & Scheraga, H. A. (1975) Macromolecules 8, 750-761]. By using statistical hypothesis testing, the three lowest-energy conformations (M1, M2, and M3) were shown to give the best fit with the experimental data. All other conformations (M4-M9) were found to be inconsistent with the experimental data.     

Specific binding of eukaryotic initiation factor 2 to satellite tobacco necrosis virus RNA at a 5′-terminal sequence comprising the ribosome binding site

The mRNA-binding property of eukaryotic initiation factor 2 (eIF-2) was examined by studying its interaction with satellite tobacco necrosis virus (STNV) RNA carrying a ³²P-labeled 5′ end. The RNA molecules bound by limiting amounts of eIF-2 were isolated and digested with pancreatic and T1 RNases. Digestion patterns showed that the labeled STNV RNA preparation offered to eIF-2 was heterogeneous, containing more than 30 different 5′ ends; by contrast, the RNA selected by eIF-2 possessed predominantly one 5′ end, pApGpUp..., the 5′-terminal sequence of intact STNV RNA. Binding analysis of individual 5′-terminal fragments generated from isolated, intact, STNV RNA by partial digestion with T1 RNase showed that eIF-2 does not bind detectably to the 32-nucleotide fragment ending with the initiation codon AUG or to shorter ones, but it does bind the 44-nucleotide fragment that contains the ribosome binding site. In addition to the structural features localized at the 5′ end of STNV RNA, eIF-2 appears to recognize a conformation found only in larger molecules, because intact RNA and large 5-′-terminal fragments are bound preferentially over smaller ones. However, binding of short 5′-terminal STNV RNA fragments to eIF-2 is specific, as judged by competition with STNV and ribosomal RNA. Finally, binding of eIF-2 to intact STNV RNA leads to a conformational change in the RNA that greatly facilitates cleavage by T1 and P1 RNases at sites in the vicinity of the initiation region. These results show that eIF-2 interacts specifically with the 5′-terminal region of STNV RNA that contains the ribosome binding site and causes local unfolding of the RNA structure.     

Protein Z/protein Z-dependent protease inhibitor system in human non-small-cell lung cancer tissue

Introduction

NSCLC progression is often associated with VTE. Activation of factor X is an important step in blood coagulation activation in cancer patients. PZ)/ZPI contribute to direct factor Xa inhibition, and ZPI - attenuates factors IXa and XIa activity. The role of the PZ/ZPI in NSCLC is obscure. The aim of the study was to localize ZPI and PZ in NSCLC tissue in relation to factors X, IX and XI, as well as indicators of blood coagulation activation: prothrombin fragment F1 + 2 (F1 + 2) and fibrin.

Material & Methods

Immunohistochemical studies were performed on surgical NSCLC specimens employing antibodies against ZPI, PZ, coagulation factors X, IX, XI, as well as fibrinogen, F1 + 2 and fibrin. A semiquantitative analysis (acc. to immunoreactive score-IRS) was conducted.

Results

Medium expression of ZPI(IRS = 6.5), together with weak expression of PZ(IRS = 4), was observed in cancer cells. Strong or medium staining for factors IX, X, and XI(IRS = 8-9) was revealed in cancer cells. Fibrinogen(IRS = 10) and fibrin(IRS = 8) were demonstrated in tumor stroma and cancer cells. F1 + 2(IRS = 10) was localized in NSCLC cells. Endothelial cells (ECs) and tumor infiltrating macrophages (TAMs) were characterized by a positive staining for ZPI and PZ.

Conclusions

ZPI and PZ expression in NSCLC cells, ECs and TAMs may suggest a role for PZ/ZPI in the anticoagulant mechanisms at the tumor site. The presence of F1 + 2 and fibrin, along with a disproportional expression of ZPI and PZ, might point to impaired function of the coagulation inhibitory system in NSCLC tissue.     

Carbamazepine reduces short-interval interhemispheric inhibition in healthy humans

ObjectiveWe sought to elucidate the influence of centrally active drugs on interhemispheric inhibition (IHI) between primary motor cortices in healthy humans.MethodsWe therefore studied IHI before and 2 h after intake of a single oral dose of carbamazepine, dextrometorphane, lorazepam, or placebo and compared it with the well known results for short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Drugs were tested in separate sessions and in random order.ResultsWhile SICI and ICF were not altered by carbamazepine, IHI was reduced at the interstimulus interval of 8 ms. Dextrometorphane tended to enhance SICI and to reduce ICF and had no effect on IHI. Lorazepam reduced ICF as expected and enhanced IHI at the long intervals of 50 and 80 ms. A moderate trend for interhemispheric facilitation was inconsistently observed at the interval 2 ms and blocked by carbamazepine. In addition, carbamazepine increased the motor threshold.ConclusionsWe conclude that circuits mediating short interstimulus intervals of IHI are susceptible to sodium channel blockade.SignificanceThe results increase our knowledge of interhemispheric transmission.