Sweet neutron crystallography.

Extremely sweet proteins isolated from tropical fruit extracts are promising healthy alternatives to sugar and synthetic sweeteners. Sweetness and taste in general are, however, still poorly understood. The engineering of stable sweet proteins with tailored properties is made difficult by the lack of supporting high-resolution structural data. Experimental information on charge distribution, protonation states and solvent structure are vital for an understanding of the mechanism through which sweet proteins interact with taste receptors. Neutron studies of the crystal structures of sweet proteins allow a detailed study of these biophysical properties, as illustrated by a neutron study on the native protein thaumatin in which deuterium labelling was used to improve data quality.

Lack of effects of hypoglycemia on glucose absorption in healthy men.

OBJECTIVE: To assess the effects of hypoglycemia on glucose absorption by examining the systemic appearance of 3-OMG (a glucose analogue that is transported by the same mechanism as glucose) after oral administration. RESEARCH DESIGN AND METHODS: Six healthy males 22-31 yr of age were studied during a hypoglycemic (50 mg [2.7 mM]/100 ml) and a euglycemic (90 mg [5.0 mM]/100 ml) glucose clamp. At 50 min after exposure to insulin, an oral glucose load containing 20 g of glucose and 4.5 g of 3-OMG dissolved in 300 ml of tap water was administered. Insulin administration was interrupted 30 min after oral glucose administration. RESULTS: Plasma glucose was clamped at 88 +/- 1.3 mg (4.9 +/- 0.1 mM)/100 ml during euglycemia and at 50 +/- 1.9 mg (2.7 +/- 0.1 mM)/100 ml during hypoglycemia. Concentrations of glucagon, growth hormone, cortisol, and epinephrine were significantly elevated during hypoglycemia. After 60 min, circulating 3-OMG concentrations increased to zeniths of 11.4 +/- 0.2 mg (585 +/- 10.0 mM)/100 ml (hypoglycemia) and 11.6 +/- 1.1 mg (585 +/- 56.0 microM)/100 ml (euglycemia; P = 0.95). Absorption of 3-OMG was evident between 15 and 20 min after administrations in both situations. Serum insulin was significantly lower during hypoglycemia compared with the control situation (345 +/- 50 microM [hypoglycemia], 445 +/- 50 microM [euglycemia], P = 0.03). CONCLUSIONS: We conclude that hypoglycemia does not seem to affect intestinal absorption of glucose as judged by systemic appearance of 3-OMG.

Aspartame, behavior, and cognitive function in children with attention deficit disorder.

OBJECTIVE: To determine the effects of large doses of aspartame on behavior, cognition, and monoamine metabolism in children with attention deficit disorder. DESIGN: A randomized, double-blind, placebo-controlled crossover study of unmedicated children meeting Diagnostic and Statistical Manual of Mental Disorders (3rd ed) criteria for attention deficit disorder. SETTING: Behavioral assessments were performed in the child's home by their parents and in the classroom by a teacher. Cognitive tests were administered and blood drawing was performed during a 2-day inpatient admission to our Children's Study Center. INTERVENTIONS: Administration of aspartame (single morning dose, 34 mg/kg) or placebo for alternate 2-week periods. MAIN OUTCOME MEASURES: Behavioral and cognitive tests included the Matching Familiar Figures Test (MFFT), Children's Checking Task (CCT), the Airplane Test, the Wisconsin Card Sorting Test (WCST), the Subjects Treatment Emergent Symptom Scale (STESS), the Multigrade Inventory for Teachers (MIT), and the Conners Behavior Rating Scale. Blood was drawn for complete blood cell count and liver function tests, as well as amino acid, methanol, formate, serotonin, and monoamine metabolite analyses, and urine was collected for measurement of catecholamine and monoamine metabolite excretion. RESULTS: No clinically significant differences between aspartame and placebo were found for the STESS, MIT, or Conners ratings, or for the MFFT, CCT, WCST, or Airplane cognition tests. Also, no differences were noted for any of the biochemical measures, except for the expected increase in plasma phenylalanine and tyrosine following aspartame. CONCLUSIONS: The findings indicate that aspartame at greater than 10 times usual consumption has no effect on the cognitive and behavioral status of children with attention deficit disorder. In addition, aspartame does not appear to affect urinary excretion rates of monoamines and metabolites.

Outbreak of poliomyelitis-like paralysis associated with enterovirus 71.

In the summer of 1987 five children were seen at The Children's Hospital of Philadelphia because of acute onset of flaccid paralysis of an arm or leg(s). Although there were documented exposures to oral poliovirus vaccine and coxsackievirus B3 in some of the cases, the clinical, epidemiologic and laboratory findings indicate that enterovirus 71 was the common etiologic agent for this unusual outbreak of poliomyelitis-like paralysis. Of the five children three recovered completely; the other two had residual paralysis with weakness and muscle wasting. Imaging studies of the spinal cord in the two children with residual paralysis revealed defects in the ventral aspect of the spinal cord. This series of paralytic cases attributed to enterovirus 71 is the largest reported in the United States.

Aspartame has no effect on seizures or epileptiform discharges in epileptic children.

The effects of aspartame (L-aspartyl-L-phenylalanine methyl ester; APM) on the neurological status of children with well-documented seizures were examined in a randomized, double-blind, placebo-controlled, crossover study. We report on 10 children (5 boys, 5 girls, ages 5-13 yr) who were tested for 2 weeks each on APM and placebo (single morning dose, 34 mg/kg). Seven children had generalized convulsions with 4 also having absence episodes. One child had absence seizures and 2 had complex partial seizures only. On each arm of the study, children were admitted to the hospital for a standard 21-lead electroencephalogram (EEG), continuous 24-hour cassette EEG, and determination of biochemical variables in plasma and urine. Subjects completed the Subjects Treatment Emergent Symptoms Scale (STESS) and parents the Conners Behavior Rating Scale. There were no significant differences between APM and placebo in the standard EEG or 24-hour EEG. No differences were noted for the STESS or the Conners ratings, and no differences were noted for any of the biochemical measures (except for expected increases in phenylalanine and tyrosine after APM). Our findings indicate that, in this group of vulnerable children, APM does not provoke seizures.

Risk of infection following exposures to human parvovirus B19.

In response to concern about the effect of human parvovirus B19 infection of the fetus, we have developed estimates of the risk of adults becoming infected following B19 exposures at home, in schools or day-care centers, and in hospitals. These estimates can then be used with other data to estimate the risk to the fetus of a B19 exposure during pregnancy. The risk to the fetus equals the rate of maternal susceptibility to infection times the rate of maternal infection following the specific type of exposure times the rate of fetal death following maternal infection. Data from studies of outbreaks of B19 associated erythema infectiosum and aplastic crisis suggest that the risk of infection among susceptible adults following household exposure to a B19 infected person is approximately 50% and following school exposures during outbreaks of erythema infectiosum is 20% to 30%. All susceptible school staff members, not just teachers, appear to be at risk for infection during outbreaks. Additional study is needed to determine the risk of infection following exposure to B19 infected patients in the hospital. Based on these and other data we can estimate that pregnant women whose serologic status is unknown have less than 2.5% chance of suffering fetal loss after household exposure and less than 1.5% chance after school exposure.

Progressive multifocal leukoencephalopathy in persons infected with human immunodeficiency virus, San Francisco, 1981-1989.

Progressive multifocal leukoencephalopathy (PML), a rare neurological disease, has been sporadically reported in persons infected with human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome (AIDS). From January 1981 through February 1989, in San Francisco, we identified 94 HIV-infected persons with PML, of whom 48 (51%) were pathologically confirmed (as required for AIDS case reporting). These 48 patients were significantly older when diagnosed with AIDS (20% older than 50 years) than patients with AIDS without PML. The remaining 46 (49%) patients, diagnosed clinically and by neuroimaging, did not differ significantly from definitive patients in demographic or survival characteristics after PML diagnosis. We detected antibodies to JC virus, the causative agent of PML, in 9 of 14 (64%) AIDS-related patients with PML, and in 9 of 14 (64%) matched control subjects, suggesting that determination of JC virus antibody status before AIDS diagnosis does not reliably indicate which patients will contract PML. Our study shows that the proportion of patients with AIDS who contracted PML remained stable between 1981 and 1988, but increased in the first 2 months of 1989. Our findings further indicate that PML in HIV-infected patients may be underestimated by as much as 50%.

Occupational risk factors for infection with parvovirus B19 among pregnant women.

To identify exposures associated with parvovirus B19 infection during pregnancy, two groups of pregnant women were studied during an outbreak of erythema infectiosum (EI). Of 796 pregnant women from Connecticut who were tested serologically because of perceived exposure to B19, 53% (419/796) had serologic evidence of previous B19 infection, and 6% (23/376) of the rest had evidence of recent infection. Of 121 pregnant women who had not requested testing but who lived in a community where a large outbreak of EI had occurred among schoolchildren, 36% (43/121) had serologic evidence of previous infection, and only 3% (2/78) of the rest had had a recent infection. In the exposed group, 479 women returned a supplemental exposure questionnaire. The highest infection rates among susceptible women were for schoolteachers (16%, 10/64), followed by day care workers (9%, 2/22) and homemakers (9%, 4/46). Women working outside the home but not in school or day care settings had the lowest risk (4%, 3/80). This study suggests that there is risk for B19 infection in selected occupational settings and in households.

Occupational risk of human parvovirus B19 infection for school and day-care personnel during an outbreak of erythema infectiosum.

Human parvovirus B19, the cause of erythema infectiosum, has recently been associated with adverse fetal outcomes. During a large outbreak of erythema infectiosum in Connecticut, a survey was conducted on 571 (90%) of 634 school and day-care personnel to determine the risk of acquiring B19 infection. Serologic evidence of B19 infection was determined by using an enzyme-linked immunosorbent assay. Of the school and day-care personnel, 58% had evidence of previous B19 infection. The minimal rate of B19 infection in susceptible personnel during the outbreak was 19%. The risk was increased for teachers and day-care providers who had contact with younger children and with greater numbers of ill children. These results suggest that B19 infection is an occupational risk for school and day-care personnel.