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Biomedical subjects

L Jorgensen

Publications and source records attributed to L Jorgensen.

At least 19 recordsLinked to original sources

Probing insulin's secondary structure after entrapment into alginate/chitosan nanoparticles.

The aim of the present study was to probe the structural integrity of insulin after being entrapped into chitosan/alginate nanoparticles produced by ionotropic polyelectrolyte pre-gelation. By manipulating the alginate:chitosan mass ratio and the pH during nanoparticle production, desired nanoparticles with a mean size of 850 (+/-88)nm and insulin association efficiency of 81 (+/-2)% were obtained. Insulin secondary structure was assessed by Fourier transform infrared (FTIR) and circular dichroism (CD) after entrapment into nanoparticles and after release from the particles under gastrointestinal simulated conditions. FTIR second-derivative spectra and area-overlap compared to an insulin standard confirmed that no significant conformational changes of insulin occurred in terms of alpha-helix and beta-sheet content. Far-UV-CD spectra corroborated the preservation of insulin structure during the nanoparticle production procedure. The presented nanoparticulate system is a promising carrier for insulin oral delivery since it preserves insulin structure and therefore also, potentially, its bioactivity.

Administration, Oral↗

Preparing and evaluating delivery systems for proteins.

From a formulation perspective proteins are complex and therefore challenging molecules to develop drug delivery systems for. The success of a formulation depends on the ability of the protein to maintain the native structure and activity during preparation and delivery as well as during shipping and long-term storage of the formulation. Therefore, the development and evaluation of successful and promising drug delivery systems is essential. In the present review, some of the particulate drug delivery systems for parenteral delivery of protein are presented and discussed. The challenge for incorporation of protein in particulate delivery systems is exemplified by water-in-oil emulsions.

Calorimetry, Differential Scanning↗

A clinical validation of the Dysmorphic Concern Questionnaire.

OBJECTIVE: The current study addressed the concept of dysmorphic concern as a symptom that may exist in a number of disorders. The aims of the study were to: (i) validate a recently developed questionnaire that measures dysmorphic concern, the Dysmorphic Concern Questionnaire (DCQ); and (ii) evaluate the relationship of dysmorphic concern to depressed mood, social phobia, and obsessive-compulsive symptomatology. METHOD: Sixty-five psychiatric inpatients were diagnosed using the computerized version of the Composite International Diagnostic Interview (CIDI-A). They then completed the DCQ, and questionnaires measuring body dysmorphic disorder (the Body Dysmorphic Disorder Examination, or BDDE), depression, social phobia, and obsessive-compulsive disorder (OCD). The factor structure and convergent validity of the DCQ were determined, and associations with mood and anxiety symptoms explored. RESULTS: The DCQ was found to be a reliable and valid instrument that is sensitive to dysmorphic concern. Furthermore, although dysmorphic concern was associated with body dysmorphic disorder (BDD), depression, social phobia and OCD, only the score from the BDDE predicted DCQ score in a multiple regression analysis. Finally, BDD symptomatology was best defined by the presence of negative body beliefs as measured by the DCQ. CONCLUSIONS: Negative body beliefs are the hallmark of BDD. However, the existence of dysmorphic concern does not necessarily imply a diagnosis of BDD. The DCQ is a quick and efficient means of identifying dysmorphic concern in those who present with depression, OCD, social phobia or BDD.

Adolescent↗

Regulation of uncoupling protein (UCP) 2 and 3 in adipose and muscle tissue by fasting and growth hormone treatment in obese humans.

OBJECTIVE: To investigate whether the expression of uncoupling proteins (UCP2 and UCP3) was affected by a very low calorie diet (VLCD) and growth hormone (GH) treatment for 4 weeks. DESIGN: A randomized, placebo-controlled intervention study of VLCD with or without concomitant GH-treatment. SUBJECTS: Seventeen obese women (body mass index, BMI=42.1+/-1.4 kg/m2 (range 31.8-54.5 kg/m2)) treated with VLCD for 4 weeks and randomized to concomitant placebo treatment (n=9) or GH treatment (n=8). MEASUREMENTS: Fat mass and lean body mass were measured by dual-energy X-ray absorptiometry. Energy expenditure (EE) was measured by indirect calorimetry. UCP2 and UCP3 mRNA were measured in adipose tissue and skeletal muscle biopsies before VLCD and after VLCD+/-GH-treatment by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: VLCD treatment resulted in a mean weight loss of 5.23 kg+/-0.8 (P<0.01), a 4.1% decrease in EE (P<0.05) and a 24% decrease in UCP3 mRNA in adipose tissue (P<0.03), whereas adipose tissue UCP2 mRNA and skeletal muscle UCP2 and UCP3 mRNA levels were unchanged. GH-treatment had no effects on EE, changes in body weight or UCP mRNA level. In multiple regression analysis the change in EE caused by VLCD was significantly correlated with changes in adipose tissue UCP2 mRNA (r=0.66, P<0.02) and a tendency towards a significant association with the change in adipose tissue UCP3 mRNA (r=0.45, P=0.09), but not with change in body weight, skeletal muscle UCP2 or UCP3 mRNA levels. CONCLUSION: VLCD for 4 weeks decreased UCP3 mRNA expression in human adipose tissue, whereas GH-treatment had no effect on UCP expression. Multiple regression analysis demonstrated that changes in adipose tissue UCP2 and probably UCP3 mRNA were correlated with the change in EE. These findings indicate that UCPs in adipose tissue in very obese individuals might play a role for the reduction in EE observed during energy restriction.

Absorptiometry, Photon↗

Defining regions of the Y-chromosome responsible for male infertility and identification of a fourth AZF region (AZFd) by Y-chromosome microdeletion detection.

Cytogenetic and molecular deletion analyses of azoospermic and oligozoospermic males have suggested the existence of AZoospermia Factor(s) (AZF) residing in deletion intervals 5 and 6 of the human Y-chromosome and coinciding with three functional regions associated with spermatogenic failure. Nonpolymorphic microdeletions in AZF are associated with a broad spectrum of testicular phenotypes. Unfortunately, Sequence Tagged Sites (STSs) employed in screening protocols range broadly in number and mapsite and may be polymorphic. To thoroughly analyze the AZF region(s) and any correlations that may be drawn between genotype and phenotype, we describe the design of nine multiplex PCR reactions derived from analysis of 136 loci. Each multiplex contains 4-8 STS primer pairs, amplifying a total of 48 Y-linked STSs. Each multiplex consists of one positive control: either SMCX or MIC2. We screened four populations of males with these STSs. Population I consisted of 278 patients diagnosed as having significant male factor infertility: either azoospermia, severe oligozoospermia associated with hypogonadism and spermatogenic arrest or normal sperm counts associated with abnormal sperm morphology. Population II consisted of 200 unselected infertile patients. Population III consisted of 36 patients who had previously been shown to have aneuploidy, cytological deletions or translocations involving the Y-chromosome or normal karyotypes associated with severe phenotype abnormalities. Population IV consisted of 920 fertile (control) males. The deletion rates in populations I, II and III were 20.5%, 7% and 58.3%, respectively. A total of 92 patients with deletions were detected. The deletion rate in population IV was 0.87% involving 8 fertile individuals and 4 STSs which were avoided in multiplex panel construction. The ability of the nine multiplexes to detect pathology associated microdeletions is equal to or greater than screening protocols used in other studies. Furthermore, the data suggest a fourth AZF region between AZFb and AZFc, which we have termed AZFd. Patients with microdeletions restricted to AZFd may present with mild oligozoospermia or even normal sperm counts associated with abnormal sperm morphology. Though a definitive genotype/phenotype correlation does not exist, large deletions spanning multiple AZF regions or microdeletions restricted to AZFa usually result in patients with Sertoli Cell Only (SCO) or severe oligozoospermia, whereas microdeletions restricted to AZFb or AZFc can result in patients with phenotypes which range from SCO to moderate oligozoospermia. The panel of nine multiplexed reactions, the Y-deletion Detection System (YDDS), provides a fast, efficient and accurate method of assessing the integrity of the Y-chromosome. To date, this study provides the most extensive screening of a proven fertile male population in tandem with 514 infertile males, derived from three different patient selection protocols.

Female↗

Body image perception in female Mexican-American adolescents.

This study examined the relationship of body image perception to self-esteem, physical activity involvement, and body composition among female Mexican-American adolescents. Subjects (N = 254) ranged in age from 13 to 15 years, mean age 14.4, and were drawn from a predominantly Mexican-American population located in the lower Rio Grande Valley region of Texas. Data were gathered through a self-report survey instrument consisting of body image, self-esteem, and activity involvement scales and anthropometric measures to assess body composition. Results indicated significant positive relationships between body image perception and self-esteem and activity involvement and a significant negative association body image and body fat composition. Self-esteem, followed by body fat composition, exerted the strongest explanatory power of subjects, body image scores. Findings suggest that less body image distortion exists in Mexican-American adolescent females and interventions designed to promote healthy body image emphasize esteem-building and physical activity.

Adolescent↗

Initial clinical presentation of cardiac disease in asymptomatic men with silent myocardial ischemia and angiographically documented coronary artery disease (the Oslo Ischemia Study).

Data concerning the natural history of asymptomatic coronary artery disease (CAD) has been limited to epidemiologic rather than angiographic studies, thus leading to uncertainty as to whether warning symptoms and signs will identify subjects with silent myocardial ischemia before morbid events. To address this issue, 50 apparently healthy men with angiographically proven CAD and asymptomatic exercise-induced ST depression have been followed prospectively for 15 years in the Oslo Ischemia Study. Fourteen men died. The initial presenting clinical event in these 14 men was chest pain in 4 (30%)--but in only 1 case was it recognized as typical angina--silent myocardial infarction in 5 (35%) and sudden death in 5 (35%). Thirty-six men survived, with 19 developing symptoms. Overall, chest pain was the first clinical event in 22 of the total of 33 men with symptoms (66%), whereas myocardial infarction occurred in 6 (18%) and sudden death in 5 (16%). Although chest pain occurred in 22 men, it was clinically diagnosed as typical angina pectoris in only 6. These observations suggest that there is an absence of clear-cut ischemic symptoms in many asymptomatic patients before morbid events.

Adult↗

The potential of an insoluble dietary fiber-rich source from barley to protect from DMH-induced intestinal tumors in rats.

The influence of soluble and insoluble dietary fiber supplements from barley and wheat on colon cancer risk was assessed using male Sprague-Dawley rats from four weeks of age on a semipurified (AIN76A) rat diet modified to contain 20% fat of mixed animal and plant origin and 5% dietary fiber. Gastrointestinal tumors were induced with dimethylhydrazine given weekly for five weeks at 15 mg/kg body wt by subcutaneous injection, commencing four weeks after rats were established on the experimental diets. At 32 weeks of age, rats were killed and tumors assessed. The insoluble dietary fiber-rich source from barley (spent barley grain, SBG) was significantly more effective at preventing induced tumors than soluble fiber-rich commercial barley bran. There were no significant differences among the results for the other three fiber sources, which were intermediate in their influence. Both incidence of rats affected and tumor mass index were reduced, the latter significantly, when SBG was compared with commercial barley bran. SBG also produced a significant reduction in plasma cholesterol concentration (down 17%, p < 0.05) relative to wheat bran, but commercial barley bran was not different from wheat bran at this stage. Pure cellulose and outer-layer barley bran were, by comparison, only moderately effective in cancer prevention. SBG, like wheat bran, is a good source of cellulose and hemicellulose. It is also a good source of proteins, polyphenolics, fatty acids (including alpha-linolenic), vitamin E, and minerals. Further research is needed to clarify the relevance of these other factors to the differences observed.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dimethylhydrazine↗

Functional polymorphism of the HLA-DR beta III chain.

Several clusters of class II HLA genes contribute to variation in human antigen-presenting capacity. In the HLA-DR cluster, most of the variation is due to the highly polymorphic DR beta I gene. Recent work by others has shown some nucleotide and implied amino acid sequence variation in DR beta III chains, but this variation is not known to be functionally significant. We show here that two proliferating human T-cell clones define three allelic variants of DR beta III (assignment to DR beta III based on blocking of proliferation by selected monoclonal antibodies). Thus, the DR beta III locus encodes at least three alleles that are distinguishable by human T cells and most probably contribute to the human antigen-presenting repertoire. The three DR beta III alleles subdivide the "supertypic" HLA antigen DRw52 into subtypes provisionally called DRw52.1-52.3. The DR3 haplotypes studied to date have been either DRw52.1 or 52.2; DR5 haplotypes have all (23 of 23) been 52.2; DRw6 haplotypes have included all three DRw52 subtypes, nearly half being 52.3. Our data, combined with other published data, imply that DRw8 must either have a fourth DRw52 subtype or be DR beta III null.

Alleles↗

Ultrastructural changes in re-endothelialized and non-endothelialized rabbit aortic neo-intima following re-injury with a balloon catheter.

The response by normal rabbit aortas to the removal of the endothelium with a balloon catheter, was compared to the response to the removal of regenerated endothelium from rabbit aortas that had been previously de-endothelialized. De-endothelialization results in the formation of a neo-intima. Thrombus formation following a second balloon catheter injury was compared among injured neo-intima that had been re-endothelialized, non-re-endothelialized neo-intima, and the subendothelium of normal vessels following a single injury. Rabbit aortas were examined by scanning electron microscopy of full circumference segments of the aorta and by transmission electron microscopy. Thirty minutes after a single de-endothelialization injury with a balloon catheter the luminal surface is covered by a monolayer of platelets adhering to the subendothelial connective tissues. Two weeks later there is neo-intimal formation and endothelial regeneration around branch vessel orifices. The remainder of the luminal surface is composed of smooth muscle cells (SMC). A balloon catheter injury to a vessel injured 2 weeks previously results in fibrin formation and platelet-fibrin microthrombi on the aortic intimal surface. The response of the aortic wall to re-injury does not seem to be related to the prior existence of endothelium. Both single and repeated injuries result in a distribution of formed elements which may depend, in part, on haemodynamic factors.

Animals↗

Intimal pits of aorta in rabbits: Imprints of vortices of blood flow?

Scanning electron microscopy of rabbit aorta showed that the intimal folds had a regular, linear pattern in areas of expected laminar flow. In areas of expected vortex formation, however, there was deviation of the fold pattern with the formation of rounded depressions or pits in the intimal surface. Platelet depositions were found in connection with some of the pits. In sections for light microscopy the pits corresponded to small areas of flattened folds of the innermost elastic membranes. It is concluded that the intimal pits probably reflect imprints of vortices of the whirling blood.

Animals↗