Effect of temperature in focal ischemia of rat brain studied by 31P and 1H spectroscopic imaging

³¹P, ¹H and lactate spectroscopic imaging was used to evaluate the effects of hypothermia on focal cerebral ischemia produced by middle cerebral artery occlusion. The effects on high energy phosphate metabolism, pH, lactate and NAA were investigated in 24 spontaneously hypertensive rats subjected to either permanent or transient ischemia. Under either normothermic (37.5°C) or hypothermic (32°C) conditions, with permanent 6-h occlusion, there was little difference between groups in either the NMR measurements or the volume of infarction. In animals that underwent 3 h of ischemia followed by 12 h of reperfusion, the ischemic changes in lactate, pH, NAA, and high-energy phosphate returned toward control values, and there was a protective effect of hypothermia (infarct volume of 211 ± 26 and 40 ± 14 mm³ in normothermic and hypothermic groups, respectively). Thus, hypothermia did not ameliorate the changes in lactate, pH, NAA, or high energy phosphate levels occurring during ischemia, however, during reperfusion there was an improvement in both the recovery of these metabolites and pathological outcome in hypothermic compared with normothermic animals.     

Breast Cancer Risk Assessment and Counseling: A Clinician's Guide

Abstract: Most individuals concerned about hereditary breast cancer risk will neither order nor benefit from genetic testing at the present time. Many will, however, seek information about their risk and testing. Risk assessment services, in addition to providing information about hereditary risk and genetic testing, need also to include assessment of non-hereditary risks, information about how to evaluate risks, early detection modalities, the etiology of cancer, and assistance in devising follow-up health care plans. Psychosocial factors, particularly those pertaining to the individual's past history with illness and beliefs about causes and prognosis, must be taken into account to provide relevant information that is understood. A case history with examples of some of the types of information that lead to informed consent in a cancer risk assessment setting is provided.     

Improved intracranial lesion characterization by tissue segmentation based on a 3D feature map

Our aim was to develop an accurate multispectral tissue segmentation method based on 3D feature maps. We utilized proton density (PD), T₂-weighted fast spin-echo (FSE), and T₁-weighted spin-echo images as inputs for segmentation. Phantom constructs, cadaver brains, an animal brain tumor model and both normal human brains and those from patients with either multiple sclerosis (MS) or primary brain tumors were analyzed with this technique. Initially, misregistration, RF inhomogeneity and image noise problems were addressed. Next, a qualified observer identified samples representing the tissues of interest. Finally, k-nearest neighbor algorithm (k-NN) was utilized to create a stack of color-coded segmented images. The inclusion of T₁ based images, as a third input, produced significant improvement in the delineation of tissues. In MS, our 3D technique was found to be far superior to that based on any combination of 2D feature maps (P < 0.001). We identified at least two distinctly different classes of lesions within the same MS plaque, representing different stages of the disease process. Further, we obtained the regional distribution of MS lesion burden and followed its changes over time. Neuropsychological aberrations were the clinical counterpart of the structural changes detected in segmentation. We could also delineate the margins of benign brain tumors. In malignant tumors, up to four abnormal tissues were identified: 1) a solid tumor core, 2) a cystic component, 3) edema in the white matter, and 4) areas of necrosis and hemorrhage. Subsequent neurosurgical exploration confirmed the distribution of tissues as predicted by this analysis.     

The natural history of untreated phenylketonuria over 20 years

Fifty-one adults with untreated phenylketonuria (PKU), have been reviewed after a 20 year interval, at ages ranging from 28.8 to 71.8 years. Five died of causes unrelated to PKU. Three severely affected individuals had shown a progressive loss of motor function and three had developed epilepsy, bringing the total with this problem to 12. No loss of abilities was apparent in 41 patients. Other health problems, including cataracts, were not frequent. Serum phenylalanine levels had decreased over the 20 year period. Untreated PKU does not generally cause progressive loss of abilities during adult life.     

Positive Outcome Expectancies and Smoking Behavior: The Role of Expectancy Accessibility

This study examined the association between smoking outcome expectancy accessibility and smoking behavior. Daily smokers completed a smoking expectancy accessibility task in which they made timed judgments to a series of positive consequences of smoking either after 6 hr deprivation or within 10 min of smoking. Participants then completed a questionnaire battery that contained assessments of smoking behavior and smoking outcome expectancies. Results of hierarchical regression analyses showed that expectancy accessibility was associated with the number of cigarettes smoked per day even when controlling for corresponding questionnaire measures of smoking expectancies. Moreover, smoking expectancy accessibility predicted urge to smoke ratings following exposure to a smoking cue after controlling for the effects of deprivation. Findings suggest that smoking expectancy accessibility may play a central role in smoking behavior and that individual differences in this attribute may be assessed directly through reaction time assessment.     

Acetylcholinesterase Adaptation to Voluntary Wheel Running is Proportional to the Volume of Activity in Fast, but not Slow, Rat Hindlimb Muscles

Chronic enhancement of neuromuscular activity by forced exercise training programmes results in selective adaptation of the G₄ acetylcholinesterase (AChE) molecular form in hindlimb fast muscles of the rat, with only minor and non-selective AChE changes in the soleus. In order to shed further light on the physiological significance of this G₄ adaptation to training, we turned to a voluntary exercise model. The impact of 5 days and 4 weeks of voluntary wheel cage running on AChE molecular forms was examined in four hindlimb fast muscles and the slow-twitch soleus from two rat strains. Inbred Fisher and Sprague– Dawley rats, placed in live-in wheel cages, exercised spontaneously for distances which progressively increased up to an average of ∼3 and 18 km/day, respectively, by the end of week 4. Fast muscles responded to this voluntary activity by massive G₄ increases (up to 420%) with almost no changes in A₁₂, so that by week 4 the tetramer became the main AChE component of these muscles. The additional G₄ was composed primarily of amphiphilic molecules, suggesting a membrane-bound state. The G₄ content of fast muscles was highly correlated with the distance covered by the rats during the 5 days before they were killed ( r = 0.850-0.879, P < 0.001 in three muscles). The soleus muscle, in turn, responded to wheel cage activity by a marked selective reduction of its asymmetric forms—up to 45% for A₁₂. This A₁₂ decline, already maximal by day 5 of wheel cage running, showed no relationship with the distance covered. The present results constitute strong new evidence suggesting that the role of AChE in neuromuscular transmission is not limited solely to the rapid inactivation of just-released acetylcholine.     

Joint capsule matrix turnover in a rabbit model of chronic joint contractures: Correlation with human contractures.

To evaluate changes in matrix molecules of the joint capsule, the right knees of 24 skeletally mature female NZW rabbits were immobilized while the contralateral limb served as an unoperated control. The immobilization was discontinued at 8 weeks and the rabbits were divided among four groups (n = 6) based on the number of weeks the right knees were remobilized: 0, 8, 16, or 32. Three rabbits (six knees) that did not have operations provided normal control joint capsules. The mRNA levels for collagen types I, II, and III, and MMP-1 and -13 were significantly increased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. In contrast, the mRNA levels for TIMP-1, -2, and -3 were decreased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. The mRNA levels for lumican and decorin were increased in the joint capsules of the contracture knees in all groups when compared to normal capsules. Many of the changes observed in this animal model are similar to those observed in human joint capsules from posttraumatic elbow contractures, supporting the value of this rabbit model.     

Proteasome inhibitor model of Parkinson's disease in mice is confounded by neurotoxicity of the ethanol vehicle.

Defects in the ubiquitin-proteasome system have been implicated in Parkinson's Disease (PD). Recently, a rat model of PD was developed using a synthetic proteasome inhibitor (PSI), (Z-lle-Glu(OtBu)-Ala-Leu-al). We attempted to transfer this model to mouse studies, where genetics can be more readily investigated due to the availability of genetically modified mice. We treated C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 mul of 70% ethanol over a 2-week-period. We found significant decreases in nigrostriatal dopamine in PSI-treated mice compared with saline-treated mice. However, we observed similar decreases in the ethanol-treated vehicle control group. Administration of ethanol alone led to significant long-term alterations in dopamine levels. Ethanol significantly eclipses the effects of PSI in the dopamine system, and therefore is a confounding vehicle for this model.     

Establishment and characterization of a chronic infectious mononucleosislike syndrome in common marmosets

Epstein-Barr virus (EBV) was inoculated into two species of marmosets. Successful infection was established in the majority of the animals of one species, Callithrix jacchus, as evidenced by the development of high, persistent levels of antibody against virus-specific capsid and early nonstructural proteins. Antibodies also were produced against the major membrane antigen and, in some animals, against EBV nuclear antigen (EBNA) 2 but not against EBNA 1. This is the antibody profile normally noted in individuals with chronic infectious mononucleosis (IM). EBV-induced lymphoproliferation was not seen, and EBV-specific proteins were not detected in the peripheral blood lymphocytes of infected animals. Hence, EBV infection in C. jacchus apparently does not generally include extensive B-cell involvement. However, the marmosets clearly are useful as a model for EBV primary infection and also possibly for chronic IM.