A two-generation reproduction–feeding study was undertaken with Sprague–Dawley rats to ascertain the effects of ingesting chinook salmon fillets caught in the Credit River, which empties into Lake ...Ontario (LO), or in the Owen Sound region of Lake Huron (LH). Rats (30/sex/group) were randomly assigned to groups whose dietary protein consisted of casein and/or lyophilized salmon Group 1: 20% casein (controls); Group 2: 15% casein + 5% LO salmon (LO-5%); Group 3: 20% LO salmon (LO-20%); Group 4: 15% casein + 5% LH salmon (LH-5%); Group 5: 20% LH salmon (LH-20%). After 70 days on test, the males and females were mated on a 1:1 basis within diet groups. Approximately 70 days postweaning, one F1male and one F1female from 24 litters were mated within diet groups, avoiding sibling matings. At weaning, the F0and F1adults and the F1and F2neonates not randomly selected for further testing were necropsied. Evaluated parameters included growth, feed consumption, organ weights, reproduction indices, serum chemistry, hematology, and coagulation times. The only statistically significant effects which were present in both generations were increased relative liver and kidney weights of both sexes in the LO-20% and LH-20% groups; the LH-20% females had lower alanine transaminase activity than the controls; the controls had lower creatinine levels than the fish groups and the LO-20% females; the LH-20% and LO-20% males had a lower blood urea nitrogen than the controls; and the LH-20% females had a heavier terminal body weight than the controls and a lower number of red blood cells, hematocrit, hemoglobin values, and mean platelet volume. There was a tendency for the fish-fed groups to grow faster, eat more feed, and have larger litters with heavier pups. Overall, there was little to suggest that the myriad of contaminants in chinook salmon from the Great Lakes presented an appreciable toxicological risk to Sprague–Dawley growth and reproduction.
25 male patients (mean age 29 yrs) in a maximum security psychiatric hospital were administered the MMPI under each of 3 sets of instructions--honest, fake-good adjustment, and fake-bad adjustment. ...As in an earlier study with inmates by P. Gendreau et al , it was found that Ss were able to fake both good and bad adjustment, but that various faking indices were reasonably accurate in detecting both. Overcontrolled-hostility (OCH) scale scores were related to scores on the faking indices, suggesting that high OCH scores may indicate a desire to appear normal on psychological testing. (13 ref)
Human immunodeficiency virus type 1 (HIV-1) was isolated from five patients with late-stage disease treated with zidovudine (ZDV) for more than 1 year. Peripheral blood mononuclear cells (PBMCs) were ...used for all virus isolations and to assay for drug resistance. The isolates exhibited a 10- to 100-fold decrease in ZDV susceptibility compared to pretreatment isolates. Multiple clones of a 618 bp segment of the HIV reverse transcriptase gene encompassing codons 60-250 were sequenced for each isolate. The association of alterations at codons Asp67---Asn, Lys70---Arg, Thr215---Phe or Tyr, and Lys219---Gln with ZDV resistance has been previously noted (ref. 5). In this study, the most frequent alterations was Thr215---Tyr although genotypic mixtures of Thr/Tyr and Phe/Tyr were also observed. One isolate with a Tyr215 alteration and unaltered codons at 67, 70, and 219 had high-level ZDV resistance. Alterations at codons 67, 70, and 219 did not appear to increase resistance when seen in combination with Tyr215. Virus isolates obtained from each patient by cultivation with either 0 or 4 microM ZDV were compared and found to have similar alterations at codons 67, 70, 215, and 219, although one instance of apparent in vitro selection for Tyr215 over Phe215 was observed. Assays using PBMCs for virus propagation will permit susceptibility testing of HIV isolates from most patients on antiretroviral drugs to investigate the clinical significance of drug resistance.
Niemann-Pick type C is an autosomal-recessive, neurovisceral storage disorder that results from defective cholesterol esterification. Cholesterol-lowering agents have been demonstrated to decrease ...hepatic lipids in Niemann-Pick type C patients. The objective was to determine the effects of cholesterol-lowering agents on neurologic features and to develop a noninvasive method of monitoring clinical response. A 9-month-old boy with progressive hepatosplenomegaly and neurodevelopmental delay was studied. Water-suppressed proton magnetic resonance spectra from a supraventricular volume of central white and gray matter revealed an abnormal lipid signal. The patient was treated with cholesterol-lowering agents (i.e., cholestyramine, lovastatin). Repeat standardized neurodevelopmental assessments (Peabody and Griffith scales) at 13 and 19 months were normal and magnetic resonance spectra no longer detected the previously observed lipid resonance. Early treatment of Niemann-Pick type C patients with cholesterol-lowering agents appeared to have short-term beneficial effects. Magnetic resonance spectra provided a noninvasive means of monitoring CNS response.
A 1- and 5-week mouse growth study was conducted to evaluate the potential toxicological implications and nutritional value of a phosphorylated peptide, Ac-Ala-Lys(PO2Et2)-Val-OEt (a synthetic model ...resembling the covalently attached metabolite of organophosphate pesticide to protein-bound lysine), and the nonphosphorylated peptide Ac-Ala-Lys-Val-OEt. A basal diet, adequate in all nutrients except lysine (0.26%), was supplemented with 1 and 2% of the phosphorylated or the nonphosphorylated peptide, and with the amounts of crystalline lysine equivalent to those provided by the peptides. Relative lysine bioavailability was calculated by comparing growth of mice fed a peptide diet with that of mice fed basal plus an equivalent amount of crystalline lysine. Values for relative bioavailability of lysine (L-lysine = 100) in the phosphorylated peptide after 1 or 5 weeks of test were zero. Values for relative bioavailability of lysine in the nonphosphorylated peptide were, however, 100 and 86-99% after 1 and 5 weeks of test, respectively. The addition of the peptides had no significant adverse effects on relative mouse organ weights or most blood hematology parameters
A 12-month-old shorthorn heifer was presented for pollakiuria of 4 months' duration. Urinary bladder transitional cell papilloma was diagnosed. The heifer had no exposure to bracken fern and no ...papillomavirus or bacterium was demonstrated. Laser surgery was used in an attempt to debulk the mass.
The pattern of cytosolic ADP recovery after exercise has not been fully characterized in human skeletal muscle. ADP recovery after brief, ischemic exercise was studied by 31phosphorus magnetic ...resonance spectroscopy in calf muscles of 33 normal control subjects, four patients with McArdle's disease and 13 patients with mitochondrial myopathy. In normal muscle, the half‐time for the initial ADP decline was 0.18±0.07 min and was unaffected by the pH or the metabolic state at the end of exercise. ADP decreased to below rest values during the second min of recovery in 27 out of 33 control subjects. There was a significant (p<0.001) linear correlation for both the size (r=0.65) and duration (r=0.64) of this ADP undershoot with intracellular pH. Phosphocreatine resynthesis continued during the ADP undershoot. ADP undershoot was also found in patients with mitochondrial diseases (in 11 out of 13), but not McArdle's disease (six patients). Thus ADP recovery follows a complex time course that is partly dependent on pH. Only the initial ADP recovery is independent of pH, which makes it suitable for comparative assessment of muscle mitochondrial function in vivo. As phosphocreatine recovery continues during the ADP undershoot, mitochondrial regulation must be different from that at the onset of recovery. These observations are consistent with variable, changing regulators of mitochondrial metabolism in human skeletal muscle.
Glutaric acidemia type II is associated with neonatal hypoketotic hypoglycemia, metabolic acidosis, profound hypotonia, progressive cardiomyopathy, and early death. Deficiency of either electron ...transfer flavoprotein or electron transport flavoprotein: ubiquinone oxidoreductase leads to intramitochondrial accumulation of metabolites of compounds oxidized by enzymes that transfer electrons to flavoprotein. No detailed results of antemortem neuroimaging or magnetic resonance spectroscopy have been described previously. We investigated a patient with typical neonatal onset glutaric acidemia type II without obvious dysmorphogenesis or renal malformations. Cranial tomographic scan revealed hypoplastic temporal lobes and marked widening of the sylvian fissures (“bat-wing” appearance). Cranial magnetic resonance imaging documented underdeveloped frontal and temporal lobes with delayed myelination and hypoplasia of the corpus callosum.
31P-Magnetic resonance spectroscopy of muscle was grossly abnormal with a very low energy state consistent with mitochondrial dysfunction.
1H-Magnetic resonance spectroscopy of brain revealed elevated intracerebral lactate concentration and abnormally high choline/creatine ratio suggestive of dysmyelination. These findings constitute the first in vivo evidence of a developmental encephalomyopathy in glutaric acidemia type II.
We describe an infant girl who presented at age 4
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monts with developmental delay, infantile spasms, hypotonia, and elevated lactate levels in the blood and cerebrospinal fluid. She had minor ...dysmorphic features. Muscle phosphorus magnetic resonance spectroscopy demonstrated reduced phosphocreatine and increased inorganic phosphate, suggesting a defect in oxidative energy metabolism. Pyruvate dehydrogenase activity in cultured fibroblasts was reduced (0.35 nmol/ mg mitochondrial protein/min; controls 0.7–1.1 nmol/mg mitochondrial protein/min). Immunoblotting demonstrated a reduced amount of pyruvate dehydrogenase (PDH) E1α immunoreactive protein with normal amounts of E2 protein. Single-strand conformational polymorphism analysis of E1α cDNA prepared from fibroblasts disclosed an abnormal migration pattern, suggesting heterozygosity for a mutant allele. Dideoxy-fingerprinting of PCR-amplified genomic DNA was used to localize the mutation to exon 10. Direct sequencing demonstrated a novel 13-bp insertion mutation that would lead to premature termination of the protein product. This study further extends the allelic heterogeneity underlying PDH deficiency. The demonstration of bioenergetic abnormalities in muscle emphasizes that hypotonia in PDH deficiency may have combined peripheral and central etiologies. The results further suggest that the association of cerebral dysgenesis with lactic acidemia in females may be a useful clue to PDH deficiency.
