Psychological reactions among family members of patients with implantable defibrillators

OBJECTIVE: To describe psychological reactions among family members of patients receiving an implantable cardioverter/defibrillator (ICD) during the first 9 months after implantation. METHODS: Eighty-two family members (age 56+/-12 years, 74 percent female, 79 percent married, 88 percent Caucasian) of ICD patients completed questionnaires regarding their mood (Profile of Mood State), cognitive illness appraisals (Meaning of Illness Questionnaire) and coping strategies (Jalowiec Coping Scale) prior to ICD implantation, and as well as 1 and 9 months postoperatively. RESULTS: Total mood disturbance score (TMD), threat appraisal, and emotion- and problem-focused coping were highest prior to ICD implantation, and decreased during the first postoperative month showing stable values thereafter. There was no change in challenge appraisal. Multiple regression analysis found that the use of psychotropic drugs (anxiolytics, sedatives; Beta = .25), emotion-focused coping (Beta = .37), and challenge appraisal (Beta =-.21) at 1 month accounted for 26 percent of variance in TMD at 9 mon ths. CONCLUSION: A spouse's ICD implantation is a major stressful event for family members leading to a diminished mood state prior ICD implantation. Reduction in emotion-focused coping and the use of challenge appraisal may improve mood state in family members of ICD patients during early follow-up.     

Cloning of rat betacellulin and characterization of its expression in the gastrointestinal tract

Betacellulin (BTC) is relatively a more recently discovered member of the EGF family of growth factors. As a prelude to its expression and functional studies in rat models of gut damage/repair, we have cloned rat BTC and examined its expression in the gastrointestinal tract. Rat BTC was found to be nearly identical to mouse betacellulin. A single 3 kb mRNA species was detected by Northern blotting, and ribonuclease protection analysis showed that its expression was ubiquitous but low in abundance throughout the gut. BTC mRNA and protein were found expressed in the gastric surface and upper pit epithelium as well as in some cells of gastric glands. In the jejunum, BTC mRNA and protein were localised to the crypt epithelium and in villous goblet cells. In the colon, BTC mRNA and protein were found produced in crypt and surface epithelium as well as in goblet cells. Taken together, the wide spread expression in the gut epithelium and in mucous cells in particular suggests an important and unique role for BTC in the gastrointestinal tract.     

Structure and function of the proteins of the mammalian Zona pellucida

The zona pellucida (ZP) is the extracellular matrix that plays important roles in sperm-egg interaction. The ZP is composed of three major glycoproteins that exhibit heterogeneity due to extensive post-translational modifications including glycosylation and sulfation. Because of these modifications the nomenclature of ZP proteins from different species based on electrophoretic mobilities has been confusing. As the cDNAs and genes encoding the different ZP proteins have been isolated and sequenced, it is now possible to relate these ZP proteins according to gene families. Using the mouse ZP nomenclature, the ZP proteins from different mammalian species can be classified into three protein families: ZP1, ZP2, and ZP3. Although some of the structural domains of the ZP proteins of different species are conserved within each family, they exhibit distinct biological properties. In the mouse it has been established that ZP3 is the primary sperm receptor while ZP2 has secondary sperm receptor properties. In the pig, however, ZP1 has been shown to have sperm receptor activity similar to that observed in the rabbit and nonhuman primates. It is of interest that the human ZP2 and ZP3 gene families are 60-70% conserved with respect to the mouse ZP amino acid sequence, while the mouse ZP1 is only 39% conserved with respect to human ZP1. Such differences in protein structure and glysosylation may explain the marked species differences in the biochemical, physicochemical and immunochemical properties of the ZP. Studies have now shown that the proteins of the ZP are expressed in a stage specific manner and that there is increasing evidence that ZP proteins are expressed by both granulosa cells and the oocyte and may play a role in granulosa cell differentiation.     

Short stature with pigmentation

Four hypomelic children of abnormally short stature had slight intellectual defect, melanotic skin, and some facial features in common. 3 were followed to the age of 23-26 years, and they remained small and pigmented.     

The role of presurgical expectancies in predicting pain and function one year following total knee arthroplasty

The present study examined the prospective value of response expectancies (ie, pain, sleep) and behavioral outcome expectancies (ie, return to function) in the prediction of pain severity and functional limitations 12 months after total knee arthroplasty (TKA). The study sample consisted of 120 individuals (73 women, 47 men) with osteoarthritis of the knee who were scheduled for TKA. Measures of expectancies, pain severity, pain catastrophizing, pain-related fears of movement, and depression were completed prior to surgery. Participants also completed measures of pain severity and functional limitations 12 months following surgery. Analyses revealed that behavioral outcome expectancies were stronger predictors of follow-up pain and functional limitations than response expectancies. Consistent with previous research, analyses also revealed that pain catastrophizing, pain-related fear of movement, and depression predicted follow-up pain and function. In a multivariate analysis, only pain catastrophizing contributed significant unique variance to the prediction of follow-up pain and function. Behavioral outcome expectancies partially mediated the relation between catastrophizing and follow-up pain and function. The relation between catastrophizing and follow-up pain severity and functional limitations remained significant even when controlling for behavioral outcome expectancies. The results suggest that interventions designed to specifically target behavioral outcome expectancies and catastrophizing might improve post-surgical outcomes.     

Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B)

Sanfilippo B syndrome is caused by a deficiency of alpha-N- acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes results in degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. In order to clone the deficient gene, we purified the enzyme from human placenta and obtained amino acid sequence information. Alignment of one of the CNBr generated internal peptides to sequence from the database revealed the chromosomal location of the gene in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase at 17q21.1. The available DNA sequence was used to clone the cDNA coding for alpha-N- acetylglucosaminidase and analyse its gene structure. The gene is fully contained in the 5' upstream flanking region of the gene for 17-beta- hydroxysteroid-dehydrogenase and interrupted by five introns. The cDNA clone has a length of 2575 bp and encodes a protein of 743 amino acids. Chinese hamster ovary cells transfected with the cDNA construct show alpha-N-acetylglucosaminidase activity about 17-fold over background. This will allow correction studies with NAG deficient Sanfilippo B cell lines and facilitate the development of enzyme replacement therapy for these patients.      

Adeno-associated virus serotype 2-mediated gene transfer to the parotid glands of nonhuman primates

Salivary glands (SGs) are promising gene transfer targets with potential clinical applicability. Previous experiments in rodents using recombinant serotype 2 adeno-associated viral (rAAV2) vectors have demonstrated relatively stable transgene-encoded protein levels after SG gene transfer. In the present study, we examine direct SG administration of rAAV2 vectors encoding rhesus macaque erythropoietin (RhEPO) to the parotid glands of nonhuman primates using two different doses (n = 3 per group; 1 x 10(10) or 3 x 10(11) particles/gland, respectively). Gene transfer had no negative effects on general macaque physiology (e.g., weight, complete blood count, and serum chemistry). Macaques were euthanized 6 months after vector administration and complete necropsy and pathology assessments were performed, revealing no vector-related pathological lesions in any of the examined organs. In the high-dose group, RhEPO expression increased quickly (i.e., by week 1) and levels remained relatively stable both in serum and saliva until the end of the study. Serum-to-saliva ratios of RhEPO revealed secretion of the transgene product into the bloodstream, but not to the extent previously observed in mice. Furthermore, the kinetic results were not predicted by those observed in murine SGs. With respect to viral biodistribution, at necropsy vector was found overwhelmingly in the targeted parotid gland ( approximately 100 times more than levels in other tissues, most of which were similar to tissue levels in nontreated animals). We conclude that administration of modest doses of rAAV2 vectors to SGs for therapeutic purposes can be accomplished without significant or permanent injury to the targeted gland or to distant organs of nonhuman primates.