Sex differences in weight loss among adults with Type II diabetes mellitus

The treatment of choice for Type II or non-insulin-dependent diabetes mellitus is a behavioral program for the management of weight. However, compliance with this lifelong dietary regimen is often poor. In the current investigation male and female adults with diagnosed Type II diabetes were randomly assigned to either a behavior modification, a cognitive modification, a cognitive-behavior modification, or a control group. Patients were evaluated in terms of weight, percentage of body fat, and glycosylated hemoglobin measures. Men lost signficantly more weight than women and subjects in the behavior modification group lost more weight and demonstrated greater decreases in diabetes control than subjects in the cognitive-behavior modification, cognitive, and control groups. A significant interaction indicated that diabetic men may benefit more from behavioral weight reduction programs than diabetic women. Several explanations for these findings are considered.This work was supported by Grants K04 HL 00809 and R01 AM 27901 from the National Institutes of Health to Robert M. Kaplan.     

Two novel paradigms for the simultaneous assessment of conditioned taste aversion and food intake effects of anorexic agents

The conditioned taste aversion (CTA) is routinely used to assess the aversive consequences of anorexic agents, including potential pharmacological therapies for obesity. In a typical CTA paradigm, rats briefly sampling a novel tastant (e.g., saccharin) are acutely administered with toxin (e.g., lithium chloride, LiCl). After as few as one taste-toxin pairing, rats will reliably avoid the novel tastant. This paradigm is frequently used for the assessment of possible aversive consequences of drugs that are candidates for pharmacological therapies. The degree to which the drug supports development of a CTA is interpreted as an index of its aversive properties. Difficulties with previous work include the inability to assess affects on food intake and CTA simultaneously, particularly during chronic drug administration. We report here two novel CTA paradigms for the assessment of appetitive and aversive consequences of anorexic agents, simultaneously. In the first experiment, animals receive an intraoral infusion of a novel and highly palatable tastant immediately prior to administration of increasing doses of LiCl. In the second experiment, rats were implanted intraperitoneally with osmotic minipumps that chronically delivered a low dose of LiCl for 7 days. LiCl did not affect short or long term food intake in either experiment. However, LiCl did support the development of a CTA in both paradigms. These results suggest that both the appetitive and aversive consequences of anorexic agents can be assessed simultaneously during either acute or chronic drug administration.     

Inhibition of tumor necrosis factor in the brain suppresses rabbit sleep

Tumor necrosis factor (TNF) is a cytokine that possesses many biological activities, including enhancement of non-rapid-eye-movement sleep (NREMS). The role of endogenous TNF in the regulation of spontaneous sleep is unknown. If TNF is involved in sleep regulation, then reduction of endogenous TNF should suppress spontaneous sleep. A soluble TNF-binding protein I (TNF-BP I) and a synthetic fragment of TNF-BP I, TNF-R-(159–178), that contains the biologically active region of TNF-BP I, were used. These substances bind TNF and possess TNF-inhibitory activity; their effects on rabbit sleep after intracerebroventricular injection were determined across a 6-h recording period. Two doses of TNF-BP I (0.05 g and 0.5 g) were administered; the higher dose of TNF-BP I significantly decreased NREMS. Four doses of TNF-R-(159–178) (0.25 g, 2.5 g, 25 g and 50 g) were used. The 25 g and 50 g doses significantly suppressed NREMS. The highest dose (50 g) also decreased REM sleep. These results are consistent with the hypothesis that endogenous brain TNF is involved in the regulation of normal sleep.     

DNA microarray analysis reveals novel gene expression profiles in collagen-induced arthritis

Global gene expression was analyzed in early and late collagen-induced arthritis (CIA). Of 8734 cDNAs analyzed, 330 were induced and 55 downregulated greater than twofold in early or late disease. Hierarchical clustering of these 385 cDNAs demonstrated five distinct expression patterns differentiating early from late disease and correlating with histopathologic changes in the paw. Of the 385 cDNAs, 185 are known, characterized genes, the majority of which are not described as playing a role in arthritis. However, several of these genes are involved in pathological processes relating to arthritis, including apoptosis, inflammation, and cellular proliferation. One interesting gene, follistatin-like gene, is highly expressed along the margin of contact between inflammatory synovial pannus and eroding bone, suggesting a role in joint destruction. These results demonstrate that global gene expression profiles distinguish early and late CIA and reveal several genes novel to arthritis the further characterization of which will advance our understanding of arthritis.     

Gliding motility leads to active cellular invasion by Cryptosporidium parvum sporozoites

We examined gliding motility and cell invasion by an early-branching apicomplexan, Cryptosporidium parvum, which causes diarrheal disease in humans and animals. Real-time video microscopy demonstrated that C. parvum sporozoites undergo circular and helical gliding, two of the three stereotypical movements exhibited by Toxoplasma gondii tachyzoites. C. parvum sporozoites moved more rapidly than T. gondii sporozoites, which showed the same rates of motility as tachyzoites. Motility by C. parvum sporozoites was prevented by latrunculin B and cytochalasin D, drugs that depolymerize the parasite actin cytoskeleton, and by the myosin inhibitor 2,3-butanedione monoxime. Imaging of the initial events in cell entry by Cryptosporidium revealed that invasion occurs rapidly; however, the parasite does not enter deep into the cytosol but rather remains at the cell surface in a membrane-bound compartment. Invasion did not stimulate rearrangement of the host cell cytoskeleton and was inhibited by cytochalasin D, even in host cells that were resistant to the drug. Our studies demonstrate that C. parvum relies on a conserved actin-myosin motor for motility and active penetration of its host cell, thus establishing that this is a widely conserved feature of the Apicomplexa.     

Nature of telomere dimers and chromosome looping in human spermatozoa

Specific and well-organized chromosome architecture in human sperm cells is supported by the prominent interactions between centromeres and between telomeres. The telomere-telomere interactions result in telomere dimers that are positioned at the nuclear periphery. It is unknown whether composition of sperm telomere dimers is random or specific. We now report that telomere dimers result from specific interactions between the two ends of each chromosome. FISH using pairs of subtelomeric DNA probes that correspond to the small and long arms of seven human chromosomes demonstrates that subtelomeres of one chromosome are brought together. Statistical analysis confirmed that telomere associations could not result from the random proximity of DNA sequences. Therefore, chromosomes in human sperm nuclei adopt a looped conformation. This higher-order chromosome structure is most likely required for chromosome withdrawal/decondensation during the early fertilization events leading to zygote formation. These individuals contributed equally to the work     

Reliability and validity of dyspnea measures in patients with obstructive lung disease

Dyspnea, the clinical term for shortness of breath, is the primary symptom and an important outcome measure in evaluations of patients with lung disease. It is a subjective symptom that has proved difficult to quantify. Many dyspnea measures are available, yet it is difficult, based on the existing literature, to determine the most reliable and valid. In this study, we evaluated 6 measures of dyspnea for reliability and validity: (a) Baseline Dyspnea Index (BDI) and Transition Dyspnea Index, (b) UCSD Shortness of Breath Questionnaire (SOBQ), (c) American Thoracic Society Dyspnea Scale, (d) Oxygen Cost Diagram, (e) Visual Analog Scale, and (f) Borg Scale. Subjects were 143 patients (74 women and 69 men) with obstructive lung disease, ages 40 to 86, FEV., 0.36 to 3.53 L, FVC 1.07 to 5.74 L. Dyspnea measures were assessed for test-retest reliability, internal consistency, interrater reliability, and construct validity (i.e.. correlations among dyspnea measures and correlations of dyspnea measures with exercise tolerance, health-related quality of life, lung function, anxiety, and depression). Results suggest that the SOBQ and BDI demonstrated the highest levels of reliability and validity among the dyspnea measures examined. This research was supported by University of California Tobacco Related Disease Research Program Grant 2RT026S, National Heart. Lung, and Blood Institute Grant HL 34732 to Robert M. Kaplan, and National Institutes of Health NHLBI Preventive Pulmonary Academic Award No. HL02215 to Andrew L. Ries.     

Phase Variation of Campylobacter jejuni 81-176 Lipooligosaccharide Affects Ganglioside Mimicry and Invasiveness In Vitro

The outer cores of the lipooligosaccharides (LOS) of many strains of Campylobacter jejuni mimic human gangliosides in structure. A population of cells of C. jejuni strain 81-176 produced a mixture of LOS cores which consisted primarily of structures mimicking GM(2) and GM(3) gangliosides, with minor amounts of structures mimicking GD(1b) and GD(2). Genetic analyses of genes involved in the biosynthesis of the outer core of C. jejuni 81-176 revealed the presence of a homopolymeric tract of G residues within a gene encoding CgtA, an N-acetylgalactosaminyltransferase. Variation in the number of G residues within cgtA affected the length of the open reading frame, and these changes in cgtA corresponded to a change in LOS structure from GM(2) to GM(3) ganglioside mimicry. Site-specific mutation of cgtA in 81-176 resulted in a major LOS core structure that lacked GalNAc and resembled GM(3) ganglioside. Compared to wild-type 81-176, the cgtA mutant showed a significant increase in invasion of INT407 cells. In comparison, a site-specific mutation of the neuC1 gene resulted in the loss of sialic acid in the LOS core and reduced resistance to normal human serum but had no affect on invasion of INT407 cells.