Prospects for insulin delivery by ex-vivo somatic cell gene therapy

The principle of insulin delivery by ex-vivo somatic cell gene therapy involves the removal of non-B-cell somatic cells (e.g. fibroblasts) from a diabetic patient, and genetically altering them in vitro to produce and secrete insulin. The cells can be grown in culture and returned to the donor as a source of insulin replacement. Cells modified in this way could be evaluated before implantation, and reserve stocks could be cryopreserved. By using the patient's own cells, the procedure should obviate the need for immunosuppression and overcome the problem of tissue supply, while avoiding a recurrence of cell destruction. Ex-vivo somatic cell gene therapy requires an accessible and robust cell type that is amenable to multiple transfections and subject to controlled proliferation. Special problems associated with the use of non-B-cell somatic cells include the processing of proinsulin to insulin, and the conferment of sensitivity to glucose-stimulated proinsulin biosynthesis and regulated insulin release. Preliminary studies using fibroblasts, pituitary cells, kidney (COS) cells and ovarian (CHO) cells suggest that these challenges could be met, and that ex-vivo somatic cell gene therapy offers a feasible approach to insulin replacement therapy.     

Air Drying Characteristics of Apricots

The optimization of the drying of apricots was studied using four treatments: (1) blanching and drying; (2) sulfiting-blanching and drying; (3) blanching-sulfiting and drying; and (4) sulfiting-drying to 50% moisture-blanching and finish drying. Levels of sulfiting were from 0–2000 ppm SO₂ and drying was done at 50° to 80°C. The quality of dried apricots was judged by extent of browning development and hardness determination. A surface response statistical design was applied to evaluate the optimum drying conditions. Sulfiting-drying, using 80–1000 ppm SO₂ at any temperature in the range 50–80°C, was found to be the best treatment. Thus, sulfite was the major factor in controlling dry apricot quality and would be hard to reduce. Drying time was reduced by 50% when apricots were dried at 80°C compared to 50°C, and blanching reduced the time by 10 to 20%. Loss of SO₂ was greater than 50% for all treatments.     

Smoking and Parkinson''s disease: a dose-response relationship

BACKGROUND: Previous studies questioned the link between early childhood anemia and detrimental child development. OBJECTIVE: A population-based study was conducted to examine the association between early childhood anemia and mild or moderate metal retardation at 10 y of age. DESIGN: The present study linked early childhood nutrition data collected by the Special Supplemental Program for Women, Infants, and Children (WIC) and school records. Hemoglobin values were used to determine the relation between anemia in early life and children's placement in special education classes for mild or moderate mental retardation. Subjects were all participants in the WIC program. A computer program was used to link data from birth, WIC, and school records. RESULTS: Logistic regression showed an increased likelihood of mild or moderate mental retardation associated with anemia, independent of birth weight, maternal education, sex, race-ethnicity, the mother's age, or the child's age at entry into the WIC program. CONCLUSION: These findings support the proposition that efforts to prevent mild and moderate mental retardation should include providing children with adequate nutrition during early childhood.     

In situ reflectance measurements and TM data of some sedimentary rocks with emphasis on white sandstone,southwestern Sinai,Egypt

This work presents the results of in situ reflectance measurements and Landsat-TM data analysis for some sedimentary rocks exposed in southwestern Sinai. Particular emphasis was given to white sandstone. In situ reflectance measurements were carried out in four selected sites (Musaba Salama, Abu Natash, El Dehisa and Abu Qafas areas) to define the distinctive surface reflectance patterns caused by the abundance of silicates, carbonates, clay minerals and iron oxides in white sandstone and other sedimentary rock types (clay, kaolin, limestone and dolomite). Moreover, in situ measured radiometric data were used to establish the theoretical basis for lithological discrimination.

Enhanced band ratios (2/3, 3/4, 4/5 and 5/7) and colour stretched ratio composite (2/3, 3/4 and 5/7) of the TM data 25 January 1984 of the Musaba Salama area were utilized to identify rocks rich in silicates and thereby to distinguish the white sandstone. The results demonstrated that the processed TM data can be used reliably in arid regions to distinguish white sandstone from other sandstone varieties as well as other rock types (limestone, dolomite, kaolin and shale).     

Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin

Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine repeat in the HD protein huntingtin. Huntingtin's localization within the cell includes an association with cytoskeletal elements and vesicles. We previously identified a protein (HAP1) which binds to huntingtin in a glutamine repeat length-dependent manner. We now report that HAP1 interacts with cytoskeletal proteins, namely the p150 Glued subunit of dynactin and the pericentriolar protein PCM-1. Structural predictions indicate that both HAP1 and the interacting proteins have a high probability of forming coiled coils. We examined the interaction of HAP1 with p150 Glued . Binding of HAP1 to p150 Glued (amino acids 879-1150) was confirmed in vitro by binding of p150 Glued to a HAP1-GST fusion protein immobilized on glutathione-Sepharose beads. Also, HAP1 co-immunoprecipitated with p150 Glued from brain extracts, indicating that the interaction occurs in vivo . Like HAP1, p150 Glued is highly expressed in neurons in brain and both proteins are enriched in a nerve terminal vesicle-rich fraction. Double label immunofluorescence experiments in NGF-treated PC12 cells using confocal microscopy revealed that HAP1 and p150 Glued partially co-localize. These results suggest that HAP1 might function as an adaptor protein using coiled coils to mediate interactions among cytoskeletal, vesicular and motor proteins. Thus, HAP1 and huntingtin may play a role in vesicle trafficking within the cell and disruption of this function could contribute to the neuronal dysfunction and death seen in HD.     

Role of diameter differences among follicles in selection of a future dominant follicle in mares

Follicles > or = 5 mm were ablated in pony mares by a transvaginal ultrasound-guided technique on Day 10 (ovulation = Day 0). Follicle emergence (at 15 mm, experiment 1; at 6 mm, experiment 2) and development of the new wave was monitored by transrectal ultrasound. Deviation was defined as the beginning of a marked difference in growth rates between the two largest follicles. In experiment 1, mares were grouped (n = 4 per group) into controls, ablation-controls (ablations at Day 10 only), and a two-follicle model (periodic ablation sessions so that only the two largest follicles developed). There were no significant indications that the two-follicle model altered follicle diameters, growth rates, or time intervals of the two retained follicles at or between events (follicle emergence, deviation, and ovulation). In experiment 2, the two-follicle model (n = 14) was used for follicle and hormonal characterization and hypothesis testing, without the tedious and error-prone necessity for tracking many (e.g., 20) individual follicles. The future dominant follicle emerged a mean of 1 day earlier (p < 0.008) than the future subordinate follicle, the growth rates for the two follicles between emergence and deviation (6 days later) did not differ, and the dominant follicle was larger at the beginning of deviation (23.1 +/- 0.8 mm versus 19.6 +/- 0.9 mm; p < 0.0001). Mean FSH and LH concentrations increased (p < 0.05) concomitantly from emergence of the future dominant follicle and peaked 3 days later when the follicle was a mean of 13 mm. Thereafter, the two hormones disassociated until ovulation: FSH decreased and LH increased. Results supported the hypothesis that the future dominant follicle has an early size advantage over future subordinate follicles and indicated that the advantage was present as early as 6 days before deviation.     

Structural reorganization of the cerebral capillary wall in the Baikal seal Pusa sibirica during diving]

INTRODUCTION: The most common fat-suppressed sequence used to study skeletal conditions is the STIR sequence which has shown high sensitivity in the detection of skeletal lesions and whose main drawback is its long acquisition time. Currently, Turbo-STIR (T-STIR) sequences can shorten the acquisition time. The purpose of this study was therefore to compare the conventional STIR sequence with the new T-STIR sequence in the study of skeletal conditions to compare their diagnostic yield. MATERIAL AND METHODS: Twenty patients with different types of skeletal lesions were examined. MR examinations were performed with a Philips Gyroscan S15/ACS II unit (1.5 T). All the patients underwent a STIR sequence (TR/TE = 1500/20, TI = 180 ms, matrix = 204 x 256, NEX = 2, slice thickness = 5 mm, acquisition time = 9 min 24 s) and a T-STIR sequence (TR/TE = 1500/20, TI = 180 ms, matrix = 204 x 256, NEX = 2, slice thickness = 5 mm, TFL = 3, acquisition time = 3 min 33 s). The images were evaluated by measuring both quantitative parameters--percent contrast (%C), contrast to noise ratio (C/N), signal to noise ratio (S/N)--and qualitative parameters--lesion conspicuity, margins and extension, motion artifacts, image quality. RESULTS: The only statistically significant difference between the two sequences was image quality, which was superior in the conventional STIR sequence (p < .05). No statistically significant difference was demonstrated with the quantitative evaluation. DISCUSSION: In this study, T-STIR sequences were performed with low-high acquisition profile to acquire an actual echo time of 20 ms which permits to obtain optimal S/N with good spatial resolution. Therefore, T-STIR sequences with low-high acquisition profile provides better results than T-STIR sequences with linear acquisition profile which permits to obtain an actual echo time of 40 ms. CONCLUSION: This work shows that T-STIR sequences can replace conventional STIR sequences in the study of skeletal conditions reducing the acquisition time by 60%. This result can be obtained only by an accurate optimization of acquisition parameters.     

TOXICITY AND ANTIBACTERIAL EFFECT OF MACE OF MYRISTICA FRAGRANS USED IN MOROCCAN GASTRONOMY: BIOCHEMICAL AND HISTOLOGICAL IMPACT

The aril of the plant Myristica fragrans is one of the most broadly used spices in Moroccan gastronomy. This research demonstrated its antimicrobial activity against both gram-positive and gram-negative bacterial species. Likewise, its toxicity was investigated on Swiss albino mice. Mice were treated orally with 0.003 and 0.3 mg/day during 7 days. Plasmatic markers and antioxidant defense systems were assessed and histological alterations evaluated. Our results showed a significant increase in creatine phosphokinase level. The microscopic evaluation showed that mace induces morphological perturbation in mice's liver. The results also showed an inhibitory effect of glyceraldehyde 3-phosphate dehydrogenase and an important increase in the level of thiobarbituric acid reactive substances, succinate dehydrogenase activities and no change in catalase activities. All of these results show that M. fragrans at 0.3 mg/g in mice affects energy metabolism and oxidative stress.

PRACTICAL APPLICATIONS

Mace can be used as a natural antioxidant and preservative in the food industry to increase the shelf life of foodstuffs.     

HLA gene and haplotype frequencies in the North American population: the National Marrow Donor Program Donor Registry

BACKGROUND: As of May 1, 1995, the National Marrow Donor Program had a donor registry consisting of over 1.35 million HLA-typed volunteers recruited from most major cities and states in the United States. This registry represents the largest single HLA-typed pool of normal individuals in the world. METHODS: We analyzed the HLA-A, -B, -DR locus phenotypes of the National Marrow Donor Program donors in order to estimate gene and haplotype frequencies for major racial groups of the United States: Caucasian American, Asian American, African American, Latin American, and Native American. The large size of the database allowed us to calculate the frequencies of relatively rare antigens and haplotypes with more accuracy than previous studies. RESULTS: We observed 89,522 distinguishable HLA-A, -B phenotypes in 1,351,260 HLA-A, -B-typed donors and 302,867 distinguishable HLA-A, -B, -DR phenotypes in 406,503 HLA-A, -B, -DR-typed donors. Gene and haplotype frequencies differed remarkably among the five racial groups, with African Americans and Asian Americans having a large number of haplotypes that were specific to their racial groups, whereas Caucasian Americans, Latin Americans, and Native Americans shared a number of common haplotypes. CONCLUSIONS: These data represent an important resource for investigators in the fields of transplantation and population genetics. The gene and haplotype frequencies can be used to aid clinicians in advising patients about the probability of finding a match within a specific ethnic group, or to determine donor recruitment goals and strategies. The information is also a valuable resource for individuals who are interested in population genetics, selection and evolution of polymorphic human genes, and HLA-disease association.