Functional innervation of the striatum by ventral mesencephalic grafts in mice with inherited nigrostriatal dopamine deficiency

Weaver mutant mice are characterized by a decrease in striatal dopamine (DA), which is associated with a progressive loss of DA neurones in the substantia nigra. This mutant thus provides the opportunity to examine the functional effects of DA neurones grafted to the striatum in a genetic model of parkinsonism. Ventral mesencephalic tissue from normal foetuses was placed on the surface of the right dorsal striatum of adult weaver mutants. After grafting, animals were tested for methamphetamine-induced circling behaviour. Mutants with DA containing grafts displayed a significant circling bias toward the left, non-grafted side. Mutants without grafts did not display any rotational bias to either side. These results demonstrate that grafted DA containing neurones establish a functional innervation of the weaver striatum and suggest that grafting of neural tissue is a viable approach in restoring function in genetic degenerative disorders of the nigrostriatal system.     

Double-outlet right ventricle and severe systemic outflow tract hypoplasia

Double-outlet right ventricle and severe systemic outflow tract hypoplasia comprises a subset of patients in whom total correction or palliation requires complex surgical procedures in the neonatal period. Our experience with 3 patients illustrates the difficulties associated with treatment and suggests possible surgical options for this otherwise lethal variant of the Taussig-Bing syndrome.     

The role of CD4+ helper T cells in the destruction of microencapsulated islet xenografts in nod mice

Islet transplants for large numbers of patients with diabetes will require xenografts. Microencapsulation is an appealing method for islet xenografting. However, graft function has been limited by a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The purpose of this study was to elucidate the mechanism of this reaction. Poly-1-lysine-alginate microcapsules containing 4000-12,000 dog or 1800-2000 rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody) (20-30 microliters i.p. every 5 days, begun on day -7. Grafts were considered technically successful if random blood glucose (BG) was normalized (less than 150 mg/dl) within 36 hr. Graft failure was defined as BG greater than 250 mg/dl. Dog and rat islets in microcapsules normalized BG in both SZN and NOD mice within 24 hr routinely. Empty microcapsules and GK 1.5 treatments alone did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than .01). Graft biopsies showed an intense cellular reaction, composed of lymphocytes, macrophages and giant cells, and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days 65-85) demonstrated viable islets and no cellular reaction around microcapsules; 1/4 rat and 1/8 dog islet xenografts continued to function indefinitely in NOD recipients, even after cessation of GK 1.5 therapy. Prediabetic NODs receiving encapsulated dog or rat islets mounted a moderate cellular reaction to grafts. Empty microcapsules excited no cellular reaction in diabetic or prediabetic NODs. We conclude that the NOD reaction to microencapsulated xenogeneic islets is helper T cell-dependent, and that the target of this reaction is not the microcapsule itself, but the donor cells within.     

Impact of insulin on survival of cachectic tumor-bearing rats

The present study was performed to determine if a host nutritional treatment, insulin, in the absence of antitumor treatment could improve survival of cachectic tumor-bearing (TB) rats. Initially food intake and host weight were correlated with survival of untreated rats with similar size sarcomas (45-50 cm3). TB rat food intake (r = 0.69, p less than 0.0001) and host weight (r = 0.47, p less than 0.004) correlated positively with subsequent survival. Once daily neutral protamine hagedorn (NPH) insulin treatment (2 units/100 g) significantly improved food intake (p less than 0.01) and host weight (p less than 0.01) of cachectic TB rats without increasing tumor growth. Twice daily NPH insulin (2 units/100 g) maintained normal food intake of cachectic TB rats and turned a host weight loss into a host weight gain which was significantly greater than untreated controls (p less than 0.001) and all other methods of insulin administration including once daily (p less than 0.001). Twice daily NPH insulin maintained mild hypoglycemia (glucose = 84 +/- 12 mg/dl) compared to once daily NPH insulin which resulted in hyperglycemia (glucose = 140 +/- 8 mg/dl, p less than 0.001) prior to next dose. In addition, twice daily NPH insulin did not increase tumor growth. Once daily NPH insulin for 5 days during cachectic decline was well tolerated (no treatment deaths), and improved median survival of TB rats randomized to insulin (15 days) compared to controls (13 days, p = 0.06). However, twice daily NPH insulin during cachectic decline failed to improve survival because of treatment deaths.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship between panic attacks and chemical dependencies

The purposes of the present study were to (a) determine the prevalence and characteristics of panic attacks in an alcohol/drug abuse inpatient population, (b) compare patients who reported experiencing panic attacks to patients who have never experienced a panic attack on various self-report measures of psychopathology and on ratings completed by Caregivers, and (c) to examine differences within groups of panickers. One hundred forty-four patients completed the questionnaires over a 17 week period. Over 50% of the patients reported experiencing one or more attacks in the three weeks prior to testing. These panickers scored higher than non-panickers on various measures of psychopathology. Over 83% of panickers reported using alcohol to self-medicate their panic attacks with almost 72% of them believing this procedure to be effective for preventing or reducing panic attacks. Male panickers differed from female panickers on several measures as did panickers who reported their panic attacks began before the alcohol abuse compared to those who did not believe this. The mean history of panic attacks was 103.4 months while the mean history of alcohol abuse was 134.6 months.     

A mathematical model of volatile release in mouth from the dispersion of gelled emulsion particles.

This paper presents a mathematical model of in-mouth volatile release from gelled emulsion particles dispersed in a continuous aqueous phase. Data based on APCI MS-Breath analysis is presented to demonstrate the effect of particle size, oil content and oil-water partition coefficients. It is shown that in-mouth release of aroma from the dispersion of gelled emulsion particles follows a two-component kinetic equation with fast and slow components. Both the fast and slow rate constants depend on the particle size, oil content and oil water partition coefficient of the aroma. The relative amount of aroma contributing to the fast and slow components also depends on the size of the particles. In order to understand this unexpected behaviour, an analytical model was developed that considers the interplay between the mass transfer of flavour across the interface of the particles and that across the air-liquid interface. Analytical expressions for the two rate constants and the relative ratio of aroma contributing to the fast component have been derived. From this model, three regimes of in-mouth release of aroma from the dispersion of gelled emulsion particles were identified including, the emulsion regime, the transition regime and the gel particle regime. In the emulsion regime, changes in the size of gelled emulsion particles had negligible impact on the overall release. In the transition regime, the release was controlled by the interaction of flavour transfer from the particles with that across the air-water interface. In the gel particle regime, aroma release at long times was governed by the particles and that at short times was governed by the air-water interface, and the two processes were fully decoupled. A simple relationship was derived for the critical size above which the release of aroma from the dispersion of gelled emulsion particles is affected by the size of the particles.