No specific thalamic influence on cell composition, sugar or electrolytes of peripheral blood.

Cellular components, blood sugar, and serum electrolyte concentrations of chloride, sodium and potassium were analyzed serially in 20 patients who underwent either stereotactic thalamotomy, frontal internal capsulotomy or subcaudate tractotomy. No significant changes were seen during the interventions either after electrical stimulation or coagulation of the target area, but 3 h after the operation the neutrophile granulocyte count was significantly raised. This reaction reached a peak by the morning of the first posoperative day. Other cellular elements, blood sugar, and serum electrolytes remained unchanged. We believe that the leukocytosis is not a specific effect of the thalamic lesions, but a nonspecific stress reaction, similar to that seen after air encephalography.     

High contrast tumor imaging with radio-labeled antibody Fab fragments tailored for optimized pharmacokinetics via PASylation

Although antigen-binding fragments (Fabs) of antibodies constitute established tracers for in vivo radiodiagnostics, their functionality is hampered by a very short circulation half-life. PASylation, the genetic fusion with a long, conformationally disordered amino acid chain comprising Pro, Ala and Ser, provides a convenient way to expand protein size and, consequently, retard renal filtration. Humanized αHER2 and αCD20 Fabs were systematically fused with 100 to 600 PAS residues and produced in E. coli. Cytofluorimetric titration analysis on tumor cell lines confirmed that antigen-binding activities of the parental antibodies were retained. The radio-iodinated PASylated Fabs were studied by positron emission tomography (PET) imaging and biodistribution analysis in mouse tumor xenograft models. While the unmodified αHER2 and αCD20 Fabs showed weak tumor uptake (0.8% and 0.2% ID/g, respectively; 24 h p.i.) tumor-associated radioactivity was boosted with increasing PAS length (up to 9 and 26-fold, respectively), approaching an optimum for Fab-PAS₄₀₀. Remarkably, 6- and 5-fold higher tumor-to-blood ratios compared with the unmodified Fabs were measured in the biodistribution analysis (48 h p.i.) for αHER2 Fab-PAS₁₀₀ and Fab-PAS₂₀₀, respectively. These findings were confirmed by PET studies, showing high imaging contrast in line with tumor-to-blood ratios of 12.2 and 5.7 (24 h p.i.) for αHER2 Fab-PAS₁₀₀ and Fab-PAS₂₀₀. Even stronger tumor signals were obtained with the corresponding αCD20 Fabs, both in PET imaging and biodistribution analysis, with an uptake of 2.8% ID/g for Fab-PAS₁₀₀ vs. 0.24% ID/g for the unmodified Fab. Hence, by engineering Fabs via PASylation, plasma half-life can be tailored to significantly improve tracer uptake and tumor contrast, thus optimally matching reagent/target interactions.     

Hair zinc and copper: Relationship to hair type and serum concentrations in children and adolescents

The zinc and copper serum and hair concentrations of 691 3-18-y-old girls and boys previously determined as a part of the Multicentre Study of Atherosclerosis Precursors in Finnish Children and Adolescents were further analyzed in order to find a possible association between these two zinc and copper indices. The influence of hair color and the diameter of individual hair strands on hair concentrations were studied by the analysis of covariance. Hair color and serum zinc concentrations were found to be associated with hair zinc concentrations in boys. Such an association was not found for zinc and copper concentrations in girls. Hair vs serum concentrations in different age and hair color groups did not show however, a significant relationship either in copper or in zinc concentrations. The subjects with very low or high serum zinc or copper concentrations did not usually have extreme hair concentrations and vice versa. However, there were some subjects with low or high serum concentrations associated with low or high hair concentrations.     

Intraoperative electrical stimulation of the brain in patients with obsessive-compulsive neurosis

Twenty patients with intractable obsessive-compulsive neurosis were operated under local anesthesia. Each patient had a lesion produced in 1 of the 4 brain targets: anterior internal capsule, rostral cingulum, middle cingulum, and genu of the corpus callosum. Before destructive permanent lesions were produced, the target area was stimulated electrically. Stimulation gave subjective or objective reactions in 30% of the patients: diminished anxiety, 3 patients; increased anxiety, 1 patient, and motor responses, 2 patients. None experienced an obsessive reaction to stimulation. The clinical effect of surgery was usually good.     

Incompatibility of outer membrane proteins OmpA and OmpF of Escherichia coli with secretion in Bacillus subtilis: Fusions with secretable peptides

The secretion of the outer membrane proteins OmpA and OmpF of Escherichia coli has previously been found to be blocked at an early intracellular step, when these proteins were fused to a bacillar signal sequence and expressed in Bacillus subtilis. We have now fused these proteins to long secretable polypeptides, the amino-terminal portions of alpha-amylase or beta-lactamase. In spite of this, no secretion of the fusion proteins was detected in B. subtilis. With the exception of a small fraction of the beta-lactamase fusion, the proteins were cell-bound with uncleaved signal sequences. Protease accessibility indicated that the fusion proteins were not even partially exposed on the outer surface of the cytoplasmic membrane. Thus there was no change of the location compared to the OmpA or OmpF fused to the signal sequence only. We conclude that, like OmpA and OmpF, the fusion proteins fold into an export-incompatible conformation in B. subtilis before the start of translocation, which we postulate to be a late post-translational event.     

Surgical Decompression in Dogs with Thoracolumbar Intervertebral Disc Disease and Loss of Deep Pain Perception: A Retrospective Study of 46 Cases

The case details and outcome after surgical decompression of 46 dogs with thoracolumbar intervertebral disc disease with loss of deep pain perception prior to surgery were reviewed. Nineteen dogs (41.3%) recovered with a median follow-up period of 12.5 months. Recovery was defined as an ambulatory paraparesis, or better, with urinary and fecal continence. There was a better outcome in dogs with loss of deep pain for less than 24 hours prior to surgery (19/41; 46.3% recovered) than in dogs without deep pain perception for more than 24 hours (0/5; 0% recovered). Dogs with deep pain perception present at two weeks postoperatively had significantly higher success rate (8/12; 66.7% recovered) than dogs without deep pain perception at this time period (1/10; 10.0% recovered). The return of deep pain perception by two weeks postoperatively can be a useful positive prognostic indicator.     

Regulation of hepatic drug metabolism by elaidic and linoleic acids in rats.

Elaidic and linoleic acids were administered at doses of 40 and 200 mg/kg i.p. every second day for 4 weeks to rats fed a fat-free diet. The fatty acids had only a slight effect on the weight gain of the animals. The amount of microsomal protein was slightly decreased with the higher dose of linoleic acid. The higher dose level of both fatty acids decreased the microsomal phospholipid content. The relative amounts of microsomal phospholipid fatty acids were also altered due to fatty acid administration. The activity of microsomal NADPH cytochrome c reductase and microsomal cytochrome P-450 contents were decreased by the higher dose of linoleic acid. The hepatic aryl hydrocarbon hydroxylase and p-nitroanisole O-demethylase activities decreased in fatty acid-treated rats. The UDP-glucuronosyltransferase activity was also lowered after the fatty acid administration. The results suggest that fatty acid-induced changes in the activities of drug-metabolizing enzymes may be due to the microenvironmental changes of membrane-bound enzymes.     

Multidimensional plasticity in the Glanville fritillary butterfly: larval performance is temperature,host and family specific

Variation in environmental conditions during development can lead to changes in life-history traits with long-lasting effects. Here, we study how variation in temperature and host plant (i.e. the consequences of potential maternal oviposition choices) affects a suite of life-history traits in pre-diapause larvae of the Glanville fritillary butterfly. We focus on offspring survival, larval growth rates and relative fat reserves, and pay specific attention to intraspecific variation in the responses (G × E × E). Globally, thermal performance and survival curves varied between diets of two host plants, suggesting that host modifies the temperature impact, or vice versa. Additionally, we show that the relative fat content has a host-dependent, discontinuous response to developmental temperature. This implies that a potential switch in resource allocation, from more investment in growth at lower temperatures to storage at higher temperatures, is dependent on the larval diet. Interestingly, a large proportion of the variance in larval performance is explained by differences among families, or interactions with this variable. Finally, we demonstrate that these family-specific responses to the host plant remain largely consistent across thermal environments. Together, the results of our study underscore the importance of paying attention to intraspecific trait variation in the field of evolutionary ecology.     

Liver-Fat Accumulation and Insulin Resistance in Obese Women with Previous Gestational Diabetes

Objective: We determined whether fat accumulation in the liver is associated with features of insulin resistance independent of obesity. Research Methods and Procedures: We recruited 27 obese nondiabetic women in whom liver fat (LFAT) content was determined by proton spectroscopy, intra-abdominal and subcutaneous fat by magnetic resonance imaging, and insulin sensitivity by the euglycemic insulin clamp technique. The women were divided based on their median LFAT content (5%) to groups with low (3.2 ± 0.3%) and high (9.8 ± 1.5%) liver fat. The groups were almost identical with respect to age (36 ± 1 vs. 38 ± 1 years in low vs. high-LFAT), body mass index (32.2 ± 0.6 vs. 32.8 ± 0.5 kg/m²), waist-to-hip ratio, intra-abdominal, subcutaneous, and total fat content. Results: Women with high LFAT had features of insulin resistance including higher fasting serum triglyceride (1.93 ± 0.21 vs. 1.11 ± 0.09 mM, p < 0.01) and insulin (14 ± 3 vs. 10 ± 1 mU/L, p < 0.05) concentrations than women with low LFAT. The group with high LFAT also had higher 24-hour blood pressures, and lower whole-body insulin sensitivity compared with the low-LFAT group. Discussion: In obese women with previous gestational diabetes, LFAT, rather than any measure of body composition, is associated with features of insulin resistance.