Individual chaperones required for Yop secretion by Yersinia.

Pathogenic yersiniae secrete anti-host proteins called Yops, by a recently discovered Sec-independent pathway. The Yops do not have a classical signal peptide at their N terminus and they are not processed during membrane translocation. The secretion domain is nevertheless contained in their N-terminal part but these domains do not resemble each other in the different Yops. We have previously shown that YopE secretion requires SycE, a 15-kDa acidic protein acting as a specific cytosolic chaperone. Here we show that the gene downstream from yopH encodes a 16-kDa acidic protein that binds to hybrid proteins made of the N-terminal part of YopH and either the bacterial alkaline phosphatase or the cholera toxin B subunit. Loss of this protein by mutagenesis led to accumulation of YopH in the cytoplasm and to a severe and selective reduction of YopH secretion. This protein thus behaves like the counterpart of SycE and we called it SycH. We also engineered a mutation in lcrH, the gene upstream from yopB and yopD, known to encode a 19-kDa acidic protein. Although this mutation was nonpolar, the mutant no longer secreted YopB and YopD. The product of lcrH could be immunoprecipitated together with cytoplasmic YopD. lcrH therefore seems to encode a YopD-specific chaperone, which we called SycD. Determination of the dependence of YopB on SycD requires further investigation. SycE, SycH, and SycD appear to be members of a new family of cytosolic chaperones required for Yop secretion.     

Acute effects of chlorpromazine in a monkey operant behavioral test battery.

The effects of acute chlorpromazine treatment were assessed using a complex operant test battery (OTB) containing five tasks thought to depend upon processes associated with short-term memory and attention [delayed-matching-to-sample (DMTS)], color and position discrimination [conditioned position responding (CPR)], motivation [progressive ratio (PR)], time perception [temporal response differentiation (TRD)], and learning [incremental repeated acquisition (IRA)]. Adult male rhesus monkeys were tested 15 min after IV injection of saline or chlorpromazine (0.010, 0.030, 0.100, or 0.175 mg/kg). Behavioral endpoints measured included percent task completed, response rate or latency, and response accuracy. The order of task sensitivity to disruption by chlorpromazine was TRD = PR = IRA = DMTS = CPR in which sensitivity was defined as a significant alteration in any aspect of task performance. Chlorpromazine slowed response rates in all tasks except TRD but did decrease accuracy in that task. These effects were similar to those noted in previous studies of acute chlorpromazine treatment. Specific motoric effects suggested decreased task initiation at doses that left general motor ability intact. This finding is similar to that noted in parkinsonism caused by chronic chlorpromazine treatment.     

Nutritional Status Outcomes for Children: Ethnic, Cultural, and Environmental Contexts

The objective of this literature review was to explore the relationship between nutritional status outcomes among ethnically diverse children and cultural and environmental contexts. Articles from the literature on anthropometric/body composition measures, diet, and physiologic outcomes among ethnically diverse children were identified through on-line literature searches and references from articles reviewed. These studies were critically reviewed and selected if they reported findings resulting from use of accepted methodologies. Explanations consistent with evaluation of results from the studies and reports were developed by synthesis of the findings. Children from underserved, ethnically diverse population groups were at increased risk for obesity, increased serum lipid levels, and dietary consumption patterns that do not meet the Dietary Guidelines for Americans. More than 80% of all US children consume more than the recommended amount of total fat and saturated fat. These factors, which were noted during childhood, may track into adolescence, placing these children at increased risk for the early onset of chronic diseases such as non-insulin-dependent diabetes mellitus, cardiovascular disease, hypertension, and some forms of cancer. Although federally funded food assistance programs are changing rapidly, currently they provide foods that, when eaten as recommended, exceed the Dietary Guidelines for these children. Future interventions to improve the health and nutritional status of our nation's children, especially those from underserved, ethnically diverse groups, should be culturally appropriate and implemented at the levels of individuals, families, and communities. J Am Diet Assoc. 1996; 96:891-900,903.     

Acute effects of d-amphetamine in a monkey operant behavioral test battery

The acute effects of d-amphetamine were assessed using a battery of complex food-reinforced operant tasks that included responding in delayed matching-to-sample (DMTS, n = 6), conditioned position responding (CPR, n = 7), progressive ratio (PR, n = 8), temporal response differentiation (TRD, n = 4), and incremental repeated acquisition (IRA, n = 9) tasks. Performance in these tasks is thought to depend upon specific brain functions such as short-term memory and attention (DMTS), color and position discrimination (CPR), motivation to work for food (PR), time perception (TRD), and learning (IRA). d-Amphetamine sulfate (0.01-1.0 mg/kg IV), given 15-min pression produced significant dose-dependent decreases in the number of reinforcers obtained in each task. Response accuracy was significantly decreased at doses of 0.3 and 1.0 mg/kg for TRD and at 1.0 mg/kg for CPR when compared to saline injections. Accuracy was not consistently affected in the DMTS or IRA tasks. Response rates decreased or response latencies increased significantly at doses of 0.3 and 1.0 mg/kg in the PR and DMTS tasks. A dose of 0.1 mg/kg for the IRA and TRD tasks, 0.3 mg/kg for DMTS and 1.0 mg/kg for the CPR tasks significantly decreased percent task completed. Thus, the relative sensitivities of these tasks for detecting d-amphetamine behavioral effects were IRA = TRD greater than PR = DMTS greater than CPR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Essential Nature of Choline with Implications for Total Parenteral Nutrition

Choline is known to be important in many metabolic pathways; at this time, however, it is not considered an essential nutrient for human beings. Current evidence strongly suggests that choline is “conditionally essential,” particularly for patients receiving total parenteral nutrition (TPN). Studies in patients receiving long-term TPN have shown that low levels of plasma choline are common and can be associated with hepatic steatosis. Treatment of these patients with oral administration of choline improved plasma levels and decreased hepatic fat content; however, oral choline supplements are associated with poor compliance. More recently, investigators have evaluated intravenous administration of choline as a treatment for TPN-associated hepatic steatosis in patients with documented subnormal plasma free-choline levels. Initial results indicate that intravenous administration of choline may be an effective treatment for TPN-associated hepatic dysfunction.     

Almitrine bismesylate disposition in the human digestive tract

Summary The absorption of almitrine from the upper gastrointestinal tract has been evaluated in 6 healthy volunteers by an intubation technique. Almitrine bismesylate dissolved in malic acid was introduced into the stomach after homogenization with a meal containing the marker¹⁴C-polyethylene glycol (PEG) 4000. Unlabeled PEG 4000 was infused into the second part of duodenum throughout the experiment. Samples of the luminal content were collected every 15 min for four hours from the stomach and at the ligament of Treitz. Blood was also collected.Almitrine was neither absorbed from nor metabolized in the stomach. About 37% of the quantity of drug emptied from the stomach was absorbed from the duodenum. Almitrine was detected in plasma 50 min after ingestion of the meal and its plasma concentration-time profile reflected the cumulative gastric emptying rate. The metabolite tetrahydroxy almitrine was found in intestinal samples as soon as unchanged drug was detected in plasma. The intraluminal rate of formation of the metabolite increased with time.The results suggest hepatic metabolism of almitrine followed by rapid excretion of the metabolite in the bile.     

Day-to-Day Variation in Iron Status Indexes is Similar for Most Measures in Elderly Women With and Without Rheumatoid Arthritis

Objective To determine the day-to-day variation in biochemical measures of iron status in a group of elderly women with rheumatoid arthritis compared with a group of healthy elderly women.Design Venous blood samples were collected from each subject on 3 nonconsecutive days during a 2-week study period; subjects had fasted overnight. Variability in hemoglobin level, hematocrit value, serum iron concentration, total iron-binding capacity, transferrin saturation, serum ferritin concentration, and plasma transferrin receptor level was determined.Subjects Two groups of women, one with rheumatoid arthritis (n=10) and another that was apparently healthy (n=10).Statistical analyses Variance component analysis was used to estimate the biological variation (σ²_day) and analytic variation (σ²_rep) for each iron index. The coefficient of variation (CV) for each variance component was calculated: coefficient of biological variation = CV_day, coefficient of analytic variation = CV_rep, and coefficient of a single future determination = CV_fd.Results The CV_rep for all iron indexes was smaller than the CV_day in both groups. The CV_day was considerably higher for serum iron concentration and for transferrin saturation than for the other indexes in both groups (16.6% arid 16.6% in healthy subjects and 33.6% and 28.2%, respectively, in subjects with rheumatoid arthritis). The higher CV_day for serum iron concentration and transferrin saturation translated into a higher CV_fd for these indexes. Because of the higher variance for these two indexes, more sampling days were required for reliable estimates. CV_da and CV_fd for plasma transferrin receptor level were relatively low.Conclusions These findings corroborate our previous finding that variation of serum ferritin concentration in the elderly is lower than that demonstrated in younger populations. This aging effect persists in the presence of rheumatoid arthritis. Fasting appeared to improve reliability in the determinations for serum iron concentration and transferrin saturation. Variability estimates for the indexes other than serum iron concentration and transferrin saturation were not altered by the inflammation of rheumatoid arthritis. Plasma transferrin receptor level is a reliable index for assessing iron status in populations with rheumatoid arthritis. J Am Diet Assoc. 1996; 96:247-251.