Interest of pronostic score for optimal clinical management of obese patients.

OBJECTIVE: The aim of this retrospective study was to identify key factors favoring weight regain. METHODS: Therefore, prognostic factors for weight loss and regain have been retrieved and identified among 186 obese patients (40 +/- 2 y and 34 +/- 0.3 kg/m(2)) through the use of a simple questionnaire which considered psychological issues such as depression, anxiety and the patient's individual capacity to follow a diet. All patients have been prescribed a low-calorie diet (1200 kcal/day) being either balanced, food-combining or low-CHO. Follow-up averaged 6.4 +/- 0.3 months of which weight loss accounted for 4.4 +/- 0.1 months. RESULTS: Weight loss was similar in all 3 groups and averaged 6.0 +/- 0.2 kg. The final weight loss and weight regain results have been identical for the 3 groups. A high/bad prognostic score rating is associated with weight regain (P<0.02). Weight regain is significantly influenced by the initial weight loss speed (P<0.0001). CONCLUSIONS: The proposed prognostic score is likely to be helpful for clinicians better to profile the therapeutic approach to individualized obesity management and follow-up. Diet composition does not influence either weight loss or weight regain.

Expression of hepatitis C virus proteins does not interfere with major histocompatibility complex class I processing and presentation in vitro.

Hepatitis C virus (HCV) infection takes a chronic course in the majority of patients. The mechanisms underlying the evasion of the host immune response and viral persistence are poorly understood. In this context, we investigated interactions of HCV proteins with major histocompatibility complex (MHC) class I processing and presentation pathways using cell lines that allow the tetracycline-regulated expression of viral structural and nonstructural proteins. These well-characterized inducible cell lines were found to efficiently process and present endogenously synthesized HCV proteins via MHC class I. Functional MHC class I cell-surface expression and intracellular proteasome activity were not affected by the expression of HCV proteins. These results suggest that viral evasion of the host immune response does not involve interactions of HCV with MHC class I processing and presentation. Other mechanisms, such as interference with the interferon system, may be operative in HCV infection, leading to viral persistence.

Simultaneous nutritional cognitive--behavioural therapy in obese patients.

The most important problem in cognitive-behavioural therapies for obese patients is to initiate weight loss without reinforcing the eating-behavioural disorders. We propose to assess the cognitive-behavioural therapy in obese patients suffering from eating disorders with and without combining a nutritional approach based on fat information. The patients (n = 60) have followed a group treatment of 12 weekly cognitive-behavioural therapy sessions with or without a combined nutritional approach mainly focused on fat restriction. The scores for depression (P < 0.01), anxiety (P < 0.01) and eating disorders (P < 0.001) are significantly and similarly improved with both types of treatments. The mean weight loss is significant (P < 0.001) only after a combined nutritional cognitive-behavioural approach. The Eating Disorders Inventory (EDI) subgroup 'Drive for thinness' remains only in a combined therapy (ANOVA P < 0.01), which could explain the weight loss that only occurs in this group. Finally, the association between a cognitive-behavioural therapy and a nutritional learning process improves the anxiety and depression related to eating disorders as well as the weight loss.

Vigorous peripheral blood cytotoxic T cell response during the acute phase of hepatitis C virus infection.

After infection by hepatitis C virus (HCV), a minority of patients develop acute symptomatic disease and some of them are able to clear the virus. In this study, we analyzed peripheral blood mononuclear cells from nine patients with acute symptomatic disease with respect to their cytotoxic T lymphocyte (CTL) response using a panel of HCV-derived peptides in a semiquantitative secondary in vitro culture system. We could detect early CTL responses in 67% of these patients. The CTL responses were directed against multiple viral epitopes, in particular within the structural (core 2-9, core 35-44, core 131-140, and core 178-187) and nonstructural regions of the virus (NS3 1073-1081, NS3 1406-1415, NS4 1807-1816, NS5 2252-2260, and NS5B 2794-2802). We compared the CTL responses displayed by recently and chronically infected HLA-A2-positive patients. Virus-specific CTLs were detectable in chronic carriers but the percentage of positive peptide-specific CTL responses was significantly higher in recently infected patients (P = 0.002). Follow-up of recently infected patients during subsequent disease development showed a significant decrease in the values and proportions of positive peptide-specific CTL responses (P = 0.002 and 0.013, respectively). Patients with limited viral replication exhibited significantly more vigorous early responses (P = 0.024). These data suggest a protective role for the early antiviral CTL response in HCV infection.

CD8+ T lymphocyte responses are induced during acute hepatitis C virus infection but are not sustained.

Cellular immune responses are likely to play a key role in determining the clinical outcome in acute infection with hepatitis C virus (HCV), but the dynamics of such responses and their relationship to viral clearance are poorly understood. In a previous study we have shown highly activated, multispecific cytotoxic T lymphocyte responses arising early and persisting in an individual who subsequently cleared the virus. In this study the HCV-specific CD8+ lymphocytes response has been similarly analyzed, using peptide-HLA class I tetramers, in a further nine individuals with documented acute HCV infection, six of whom failed to clear the virus. Significant populations of virus-specific CD8+ lymphocytes were detected at the peak of acute hepatic illness (maximally 3.5% of CD8+ lymphocytes). Frequencies were commonly lower than those seen previously and were generally not sustained. Early HCV-specific CD8+ lymphocytes showed an activated phenotype in all patients (CD38+ and HLA class II+), but this activation was short-lived. Failure to sustain sufficient numbers of activated virus-specific CD8+ lymphocytes may contribute to persistence of HCV.

Molecular mimicry of human cytochrome P450 by hepatitis C virus at the level of cytotoxic T cell recognition.

Hepatitis C virus (HCV) is thought to be involved in the pathogenesis of autoimmune hepatitis (AIH) type 2, which is defined by the presence of type I antiliver kidney microsome autoantibodies directed mainly against cytochrome P450 (CYP)2D6 and by autoreactive liver infiltrating T cells. Virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) that recognize infected cells and contribute to viral clearance and tissue injury during HCV infection could be involved in the induction of AIH. To explore whether the antiviral cellular immunity may turn against self-antigens, we characterized the primary CTL response against an HLA-A*0201-restricted HCV-derived epitope, i.e., HCV core 178-187, which shows sequence homology with human CYP2A6 and CYP2A7 8-17. To determine the relevance of these homologies for the pathogenesis of HCV-associated AIH, we used synthetic peptides to induce primary CTL responses in peripheral blood mononuclear cells of healthy blood donors and patients with chronic HCV infection. We found that the naive CTL repertoire of both groups contains cross-reactive CTLs inducible by the HCV peptide recognizing both CYP2A6 and CYP2A7 peptides as well as endogenously processed CYP2A6 protein. Importantly, we failed to induce CTLs with the CYP-derived peptides that showed a lower capacity to form stable complexes with the HLA-A2 molecule. These findings demonstrate the potential of HCV to induce autoreactive CD8(+) CTLs by molecular mimicry, possibly contributing to virus-associated autoimmunity.

[Diet treatment of obesity--weight-loss stage and weight-maintenance stage]. / Le traitement diététique de l'excès pondéral--phase de perte de poids et phase de maintien du poids.

Dietetic treatment of obesity occurs in two phases one of weight reduction and one of stabilisation of the reduced weight. Results of the first phase are marked mainly by reduction of calories (quantitative aspect) and not by the carbohydrate or fat content of the diet (qualitative aspect). This improves assessment of individual nutritional preferences and sustains the patients motivation longer. Current recommendations propose less restrictive diets, i.e. 500 Kcal less than the daily allowance. In the second phase of stabilisation a diet rich in complete carbohydrates (> 50 of daily calories) and poor in lipids (< 30%) regulates metabolism, appetite sencurion of saturation and thermogenesis favorably. Such a diet seems to permit a prolonged stabilisation of weight, an important criterion for successful treatment of obesity. A diet rich in carbohydrates and poor in lipids symbolized by a nutritional pyramid is at the same time the basis for actual recommendations for the entire population.

Development and use of preprinted forms and adhesive labels in medical record charting.

Clear delineation of specific clinical and administrative responsibilities (eg, content requirements, cost constraints) is necessary in the development, approval, and implementation of effective preprinted documentation materials. Input early in the development stage from medical record and legal department staff ensures that proposed materials will meet organizational and legal standards. The development and use of time-saving preprinted documentation materials in medical record charting by the Johns Hopkins Oncology Nutrition Service is described. We conclude that the use of preprinted materials expedites and enhances both the consistency and quality of documentation.

A new peptide in the FMRFamide family isolated from the CNS of the hawkmoth, Manduca sexta.

We have purified a FMRFamide-like peptide from extracts of brain-subesophageal ganglion of the moth, Manduca sexta. The purification was monitored with a new, competitive ELISA, and accomplished with ion exchange and reverse-phase HPLC. The peptide structure was determined by a combination of tandem mass spectrometry and automated Edman degradation. The amino acid sequence of the peptide is less than Glu-Asp-Val-Val-His-Ser-Phe-Leu-Arg-Phe-amide (pEDVVHSFLRF-NH2). In a separate purification, an identical peptide was isolated from extracts of brain-associated neurohemal structures. We have named this peptide ManducaFLRFamide, to indicate its homology with other members of the "FMRFamide" family. In bioassays, chemically synthesized peptide increased the force of neurally evoked contractions in the major power-producing flight muscles, the dorsal longitudinal muscles. This observation suggests that hormonally released ManducaFLRFamide may play a role in sustaining or promoting the flight behavior necessary for mate-seeking (in males) or oviposition (in females) in sphingid moths.

Structure and innervation of the third axillary muscle of Manduca relative to its role in turning flight.

The morphology, ultrastructure, innervation and physiology of the third axillary muscle in Manduca sexta were examined to investigate the role of this muscle in flight. The muscle consists of three parts: the upper bundle, which originates on the episternum, and the middle and lower bundles, which originate on the epimeron; all three parts insert on the tip of a projection from the third axillary sclerite. The middle bundle is composed of tonic fibres, and is innervated by a single slow axon, while the other two bundles consist of intermediate fibres and are each innervated by a single fast axon. The shape and position of the third axillary sclerite within the wing hinge are such that its primary function appears to be remotion of the wing. The length of the third axillary muscle determines the amount of remotion, independency of the degree of elevation or depression of the wing and independently of the amount of remotion of the contralateral wing. Electrophysiological recordings from the three parts of the muscle during tethered flight indicate that they may each function independently of each other and in different ways. The tonic (middle) bundle is capable of maintaining tension to hold the wings in the folded position at rest and is active when the wings are folded at the end of flight. The intermediate (upper and lower) bundles are activated phasically with impulses that may occur with various relationships to the timing of activation of a direct depressor, the subalar, or of several of the elevators. The findings are consistent with the hypothesis that the third axillary muscles on both sides are important in determining the asymmetric degrees of remotion observed in turning flight.

Effects of octopamine on miniature excitatory junction potentials from developing and adult moth muscle.

Intracellular recordings of excitatory junction potentials (EJPs) and miniature EJPs (MEJPs) were made from the dorsal longitudinal muscle of Manduca sexta to determine the sites of action of octopamine. MEJPs increased in amplitude and frequency as the moth developed during the 3 days before eclosion. DL-Octopamine (5 X 10(-6) M) increased the amplitude of excitatory junction potentials in both immature moths (one day before eclosion) and adults. Octopamine (10(-5) M) also increased the amplitude and frequency of MEJPs from immature animals (one and two days before eclosion) but had the opposite effect on adults and pharate adults ready to eclose. Treatment with octopamine (10(-5) M) resulted in a decrease in input resistance and a hyperpolarization in both immature and adult muscle fibers. The results suggest that octopamine acts both presynaptically and postsynaptically but that the increase in the amplitude of the evoked response is due primarily to influences on presynaptic processes.

Effects of octopamine and forskolin on excitatory junction potentials of developing and adult moth muscle.

Intracellular recordings were made from the dorsal longitudinal muscle of Manduca sexta to determine the effects of development and octopamine on the excitatory junction potential (EJP) produced in response to electrical stimulation of the motor nerve. Observations were made on pharate moths during the last 3 days before eclosion and on adults. In saline, the highest values for EJP amplitude and maximum rate of rise and for resting membrane potential are reached on the nineteenth day of the pupal period, the day the animal ecloses; adult values are slightly lower. In animals of all ages tested, DL-octopamine (5 X 10(-6) M) increases EJP amplitude and maximum rate of rise. Increases in amplitude are greater in animals at stage day 17 and 18 than in animals at stage day 19 and adult. Octopamine has no effect on EJP rise time (onset to peak) or recovery time (peak of EJP to 70% recovery). Octopamine causes a hyperpolarization of about 6 mV. The results show that developmental changes in synapse properties are paralleled only in part by changes induced by octopamine. Both development and octopamine increase EJP amplitude and maximum rate of rise, and neither alter rise time. EJP recovery time changes with development but not in response to octopamine. Forskolin (10(-4) M) mimics the effects of octopamine on day 17 animals. EJP amplitude and maximum rate of rise are increased by forskolin, and rise time and recovery time are unaffected. Forskolin, like octopamine, causes a 6 mV hyperpolarization of the muscle fiber. These results suggest that octopaminergic modulation at the Manduca sexta dorsal longitudinal neuromuscular junction may be mediated by changes in intracellular levels of cyclic AMP.

Effects of octopamine, dopamine, and serotonin on production of flight motor output by thoracic ganglia of Manduca sexta.

Effects of biogenic amines on a centrally generated motor pattern in Manduca sexta were examined by pressure injecting nanomole to micromole amounts of octopamine, dopamine or serotonin into thoracic ganglia. Motor output was recorded extracellularly from a pair of antagonistic flight muscles and their motor neurons. The monoamines were found to alter production of a motor pattern that produces rhythmic wing flapping (10 Hz) and exhibits phase relationships similar to those in the flight pattern of intact moths. In mesothoracic ganglia with sensory nerves intact, octopamine (4 X 10(-9) mol) injected into lateral regions evoked regular firing of a single motor neuron, whereas a higher dose (4 X 10(-8) mol) often elicited the flight motor pattern. In the absence of sensory input, these doses of octopamine had little effect. Low doses (10(-10) mol) greatly enhanced motor responses to electrical stimulation of a wing sensory nerve. Dopamine (2 X 10(-10) mol) injected into the medial region of the mesothoracic ganglion elicited the flight motor pattern in the presence or absence of sensory input. Rhythmic output induced by dopamine (5 X 10(-10) mol) was suppressed by injecting serotonin (5 X 10(-10) mol) into the same region. These findings demonstrate that dopamine, octopamine, and serotonin have different effects on motor output in Manduca and suggest that these amines are involved in initiating, maintaining and terminating flight behavior, respectively. Octopamine may elicit flight production by enhancing the efficacy of sensory transmission thereby increasing excitability or arousal. Dopamine may act on interneurons involved in generating the flight motor pattern.

Octopamine enhances neuromuscular transmission in developing and adult moths, Manduca sexta.

The effect of octopamine on neuromuscular transmission was examined in developing and adult Manduca sexta. Intracellular recordings were made from the dorsal longitudinal muscle (DLM), superfused with solutions containing DL-octopamine or other amines. In untreated adult moths and pharate adults nearly ready to enclose (stage Day 19), stimulation of the motor nerve evokes a large excitatory junction potential (EJP), an active membrane response, and a twitch. In adults and Day 19 animals DL-octopamine (10(-7) to 10(-4)M) has no effect on the amplitude and rise-time of the electrical response in normal saline, but 10(-6) to 10(-4) M DL-octopamine increases the amplitude of the excitatory junction potential recorded in saline containing one-third the normal calcium concentration. Immature (Day 16) muscle, which normally produces only small EJPs following stimulation of its motor nerve, responds to 10(-6) to 10(-4) M DL-octopamine by an increase in the EJP above threshold for an active membrane response and a contraction. When the muscle has developed sufficiently to spike and contract in response to nerve stimulation in the absence of exogenous octopamine (Days 17 and 18), application of DL-octopamine increases the maximum rate at which the muscle contracts in response to each stimulus in a train (designated the maximum following frequency, MFF). The threshold dose for an effect on the MFF of Day 18 immature moths is less than 10(-10) M. At this stage 10(-8) M DL-octopamine increases the MFF four-fold. The effect on the MFF is dose-dependent over the range 10(-10) M to 10(-6) M. The biogenic amines DL-epinephrine, DL-norepinephrine, tyramine, DL-phenylethanolamine, 2-phenylethylamine, and dopamine, applied at concentrations of 10(-8) or 10(-4) M, do not change the MFF. Both DL-synephrine (10(-8) M) and serotonin (10(-7) M) mimic the action of 10(-10) M DL-octopamine on the MFF. The action of DL-octopamine (10(-7) M) is blocked by phentolamine (10(-4)M) but not by propranolol (10(-4)M). The octopamine content of hemolymph was determined with a radioenzymtic assay. The concentration of octopamine in the hemolymph increases 3.6-fold, from 5 X 10(-8) M on Day 18 (duration of adult development is 19 days) to 1.85 X 10(-7) M one day following eclosion.(ABSTRACT TRUNCATED AT 400 WORDS)

Octopamine and chlordimeform enhance sensory responsiveness and production of the flight motor pattern in developing and adult moths.

Octopamine and an agonist, chlordimeform, increase the responsiveness of adult and pharate adult Manduca sexta to gentle mechanical stimulation of the wing. Higher doses of chlordimeform elicit almost continuous production of the flight motor pattern in both adults and pharate adults, and the effect persists for more than 24 h. The dose of chlordimeform necessary for this effect increases with age. Mechanical stimulation of the wing of pharate adults elicits several cycles of flight motor pattern, but with repeated stimulation the animal habituates. Habituation is slower in chlordimeform-treated animals than in controls. Injection of octopamine (1-8 X 10(-8) mol) or chlordimeform (3 X 10(-9) mol) into the mesothoracic ganglion elicits the flight motor pattern. The excitatory actions of both compounds can be blocked by cyproheptidine. Chlordimeform (5 X 10(-8) mol) in acetone applied to the wing does not cause a noticeably greater increase in teh electrical activity of sensory neurons than does acetone applied alone; this result suggests that chlordimeform does not act on these peripheral sites or on axonal membranes in general. We suggest that chlordimeform and octopamine act on the thoracic ganglia to alter the level of excitation or effectiveness of synaptic transmission among central neurons, including those involved in producing the flight motor pattern.

United States cancer reporting laws: structure and utility.

Authorities in 52 United States jurisdictions were contacted to determine the existence and structure of cancer reporting laws and registration systems. Of the 52 US reporting areas examined; 30 (58 per cent) had a law requiring cancer reporting; 36 (69 per cent) of the reporting areas had at least one centralized cancer registry covering a geographically defined population. Among the 30 areas with cancer reporting laws, 26 had population-based registries; of the 22 areas with no cancer reporting law, 10 had a population-based registry. Among the 30 areas with cancer reporting laws, 12 required one reporting source (hospital, physician, laboratory), 11 required two reporting sources, four required three reporting sources, two areas gave the health department the authority to designate reporting sources, and one did not specify any reporting source. While 11 of the laws provided legal protection for both the data provider and the cancer patient, eight did not specify any such legal protection. While 13 laws made provisions for research uses of cancer reporting data, 17 did not do so. None of the laws had ever been legally tested at or beyond the State Appellate Court level.

Membrane structures and physiology of an immature synapse.

Immature synapses, developing moth neuromuscular junctions, were studied using electro-physiological and ultrastructural techniques, and were compared with synapses from the flight muscles of adult moths. Neuromuscular junctions, formed by short side branches of the single fast motor axon, were assessed for functional state by stimulating the nerve and recording the endplate potential intracellularly from the muscle fibre. The muscle was then fixed and prepared for scanning, thin-section, and freeze-fracture microscopy. The immature stage differs from the adult by having very small (average 7.8 mV, compared with 20-30 mV), long duration ejp's that fatigue rapidly. The immature junctions are, however, only 13% shorter than those of the adult. Within the junction, the nerve terminal comes into direct contact with the muscle membrane in a series of oval patches separated by glial processes. These regions of apposition or 'plaques' in the immature synapse are about half the diameter of the adult plaques. In freeze-fractured material, the nerve terminal membrane in the plaque region bears an irregular band of particles on the cytoplasmic leaflet; the length of the band is essentially the same in the immature synapse as in the adult. This band marks the location of the active zone, an electron dense bar of the same length in thin section. The apposing external leaflet of the muscle membrane bears a patch of postsynaptic particles; the patch is much smaller than in the adult plaque. These immature patches, presumably representing clusters of receptors, range in size from a dozen particles to a hundred or more. We consider it likely that a lack of postsynaptic receptors may partially explain the very small ejp in the developing synapse, but that other factors may also be limiting. Desmosome-like contacts between glial cells and the muscle fibre were observed. Small wisps of electron dense material appear to bridge the extracellular space between the nerve terminal and the muscle fibre or between the glial processes and the muscle fibre in some locations. They are found in the same regions of the neuromuscular junction as small groups of large particles, suggesting that these two features are different aspects of the same structure. From their location one could hypothesize that they have either a mechanical function of stabilizing the glial invaginations, or a role in communication between the three types of developing cells.

Comparison of slow larval and fast adult muscle innervated by the same motor neurone.

1. Muscles innervated by an identified set of motor neurones were compared between larval and adult stages. 2. The structure of the larval muscle is typically tonic: long sarcomeres, irregular Z-bands, and 10-12 thin filaments around each thick filament. The structure of the adult muscle is phasic: 3-4 micrometers sarcomeres, regular Z-bands, 6-8 thin filaments around each thick filament, and large mitochondrial volume. 3. The tensions produced by these muscles were correspondingly different. The larval twitch was about 7 times slower and the tetanus/twitch ratio 10 times greater than those of the adult. 4. No structural or physiological differences were observed in the neuromuscular junctions of the two stages. 5. The relatively unchanging functional relationship of a single motor neurone with two different muscle fibre types during two developmental stages is compared with the converse situation in which it has been reported that implantation of a different type of motor nerve into a muscle modifies contractile properties.