beta Gal(1-->S-4)beta GlcNac--OR: a galactosidase-stable substrate for alpha(1-->3)fucosyltransferase

1'-4 Thio-N-acetyllactosamine was chemically synthesized as a galactosidase-stable substrate for alpha(1-->3)fucosyltransferase. The product of enzymatic fucose addition was confirmed to be the thio-Le X analog.     

Cyclical vomiting as the leading symptom of regression

A 17-year old boy with primary mental retardation of unknown aetiology and cyclic vomiting syndrome (CVS) is reported. Missing an organic cause of the episodes therapeutic procedures remained symptomatic for a 15 years time period. The report focusses the CVS as a regressive mechanism triggered by a mental retardation of the child which permanently disturbed the interaction between parents and child. Psychotherapeutic approach was successful in the following respects: The advantage by illness to vomit at home was continuously reduced by admitting the boy to a hospital at every ongoing attack. Hypnotherapeutic techniques were able to substitute the "malign" regression (CVS) successively by inducing a "benign" kind of regression. Family therapy could induce new and more intense non-verbal patterns of communication which where hitherto unknown in this family.     

Autonomic dysfunction in chronic intestinal pseudo-obstruction

Mutations, other than dominant lethals, were accumulated on wild type second chromosomes (+) of Drosophila melanogaster during exposure to 50 Hz sinusoidal alternating magnetic fields of 0.5 or 5 mT (rms) for 40 generations by the Curly/Plum(Cy/Pm) accumulation method. We maintained, for 40 generations under continuous exposure, each (+) chromosome as a heterozygote with (Cy) chromosome. Viability of the (+) chromosome was tested by sib-mating of (Cy/+) male and (Cy/+) female in a culture every 10th generation to obtain the homozygote. Viability indices, defined as twice the ratio of number of (+/+) flies to that of (Cy/+) flies plus 1 in the progeny of the test mating, also were calculated, which equaled 1.00 at the starting point. For the control and 0.5 and 5 mT exposed groups, percent frequencies of recessive lethal lines, defined as a line with (+/+) flies less than 0.3% in the test mating, were, respectively, 1.9, 0.9, and 2.9% (10th), 9.0, 4.9, and 9.5% (20th), 30.3, 22.9, and 30.4% (30th), and 39.9, 32.4, and 43.3% (40th generation). For the control and 0.5 and 5 mT groups, average viability indices, excluding lethals and markedly deleterious, were, respectively, 0.778, 0.796, and 0.752 (20th), 0.704, 0.698, and 0.694 (30th), and 0.669, 0.678, and 0.595 (40th generation). Their decreasing rates were 0.0054, 0.0059, and 0.0078 per generation. No significant difference was detected among the exposure levels in either the recessive lethal mutation frequency or the viability index.     

5-Alkyl 1,2-dihydrochromeno[3,4-f]quinolines: a novel class of nonsteroidal progesterone receptor modulators

A series of nonsteroidal human progesterone receptor (hPR) agonists, 5-alkyl 1,2-dihydrochromeno[3,4-f]quinolines, was synthesized and evaluated in cotransfection and competitive receptor binding assays. The 5-alkyl substitution was shown to be responsible for the agonist activity and substitution at C9 dramatically enhanced the potency. A number of analogues in this series showed activities similar to or better than progesterone in the cotransfection and binding assays and analogue 15 exhibited similar in vivo activity as medroxyprogesterone acetate (MPA) in murine uterine wet weight/mammary gland morphology assays.     

Teenage driving fatalities

BACKGROUND/PURPOSE: A recent legislative effort in New Hampshire to institute a graduated licensing system for teenagers (TA) led to an analysis of state data on fatal crashes involving TA drivers. This provides an overview of these events and suggests possible prevention strategies. METHODS: Data on fatal crashes involving TA drivers was obtained for the years 1991 through 1996 from the Fatal Accident Unit, Division of State Police, New Hampshire Department of Safety. RESULTS: From 1991 through 1996, there were 100 events resulting in 109 total deaths, of which 76 were TA. Five involved motorcycles. Four drivers struck pedestrians, and two struck children on bicycles. In one case, an object fell from a truck, crushing a car. The remaining 88 were single- or multiple-car crashes, and these were analyzed further. Two thirds of the drivers were boys. The driver breakdown by age was 15 years, 3; 16 years, 21; 17 years, 26; 18 years, 20; 19 years, 18. The TA driver was killed in 47% of the events. Nineteen percent resulted in the death of the driver of another car. In 62 events, there were passengers in the TA's car, and in 55% of these, a passenger was killed. Twenty percent of the crashes involved drugs or alcohol, and almost two thirds of these occurred between 10:00 PM and 6:00 AM. Seat belts were not used by at least 72% of those injured fatally. In 59%, known traffic violations, usually speeding, contributed. More detailed data were available for 1995 through 1996, during which there were 30 crashes resulting in 33 deaths. Speed limit did not correlate with number of crashes. One-car crashes outnumbered multiple-car, 57% to 43%. Ninety percent occurred on single-lane roads. Most significantly, 63% of the drivers had been licensed less than 1 year and 47% less than 6 months. In this latter group, drugs and alcohol played no role, and none occurred between 11:00 PM and 6:00 AM. CONCLUSIONS: Two at-risk groups exist. The first is inexperienced sober TA drivers on single-lane roads during conventional hours. As experience increases, the second group appears: TA who have been drinking and are out late at night. Prevention strategies must take into account these two groups.     

Intoxication by star fruit (Averrhoa carambola) in six dialysis patients? (Preliminary report)

We observed six cases of patients in a dialysis programme who were apparently intoxicated by ingestion of star fruit. After ingestion of 2-3 fruits or 150-200 ml of the fruit juice, the six patients, who had previously been stable in a regular dialysis programme, developed a variety of symptoms ranging from insomnia and hiccups to agitation, mental confusion and (in one case) death. In preliminary investigations to characterize the hypothetical neurotoxin in the fruit, an extract, when injected intraperitoneally or intracerebroventricularly in rats, provoked persistent convulsions of the tonic-clonic type. It appears that star fruit (Averrhoa carambola) contains an excitatory neurotoxin. Patients with renal failure on conservative or dialysis treatment should be dissuaded from ingestion of the fruit.     

Pharmacological effects of propylthiouracil on corticosterone secretion in male rats

BACKGROUND: We investigated the direct effects of propylthiouracil (PTU) on corticosterone secretion both in vivo and in vitro. METHODS: Male rats were divided into 4 groups and then injected subcutaneously with saline, PTU, PTU plus thyroxine (T4), or T4 once daily for 2 weeks. After 2 weeks, rats were decapitated or received adrenocorticotropic hormone (ACTH), intravenously. Zona fasciculata-reticularis (ZFR) cells from normal, saline-, PTU-, PTU plus T4-, or T4-treated rats were incubated with ACTH, forskolin, 8-Br-cAMP, deoxycorticosterone (DOC) +/- PTU (1, 2, or 5 mg/mL) at 37 degrees C for 2 hours. Corticosterone concentrations in plasma and cell media, and 3':5'-cyclic adenosine monophosphate (cAMP) production in ZFR cells were determined by radioimmunoassay. The effects of PTU on the activities of steroidogenic enzymes in ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography. RESULTS: The basal and ACTH-stimulated levels of plasma corticosterone in PTU-treated rats were lower as compared to saline-treated animals. Both basal and ACTH-stimulated corticosterone secretion were inhibited by PTU > 2 mg/mL in rat ZFR cells. The cAMP production induced by forskolin was lower in PTU, PTU plus T4, or T4-treated rats than in saline-treated animals. Chronic administration of PTU or PTU plus T4 inhibited the 3 beta-hydroxysteroid dehydrogenase, 21 beta-hydroxylase, and 11 beta-hydroxylase activities. Administration of PTU (1, 2, and 5 mg/mL) suppressed the basal, ACTH, 8-Br-cAMP, forskolin, and DOC-stimulated corticosterone secretion in rat ZFR cells. Likewise, PTU > 2 mg/mL inhibited the ACTH and 8-Br-cAMP-stimulated levels of intracellular cAMP in rat ZFR cells. CONCLUSIONS: These results suggest that PTU counteracts both basal and ACTH-induced adrenal steroidogenesis through their attenuation of the activity of 11 beta-hydroxylase and cAMP production in rat ZFR cells.     

Treatment results in children with B-cell lymphomas using a modified BFM protocol

AIM: Trial of the modified protocol BFM in the treatment of children with B-cell lymphomas. MATERIALS AND METHODS: 26 children with B-cell lymphoma were treated. Of them 2 children were treated according to the program for risk 2 group and 24 children were treated as risk 3 group. RESULTS: Complete remission was achieved in 23 patients. Two children were resistant. There were 2 cases of early recurrence, 1 case of early death, 1 case of death in remission. 20 patients are in complete remission. The 4-year survival is 78%. CONCLUSION: The modified protocol BFM proved to be highly effective against B-cell lymphoma in children. Its drawback is high toxicity.     

The insulin-like growth factors (IGF) and IGF type I receptor during postnatal growth of the murine mammary gland: sites of messenger ribonucleic acid expression and potential functions

The goals of this study were to determine the cellular sites of insulin-like growth factor (IGF) and IGF type-I receptor (IGF-IR) expression and to begin to elucidate functional roles for the IGFs during postnatal development of the murine mammary gland. Using in situ hybridization analyses, we determined that IGF-I, IGF-II, and IGF-IR messenger RNAs were expressed in the highly proliferative terminal end buds during pubertal ductal growth. Consistent with these data, IGF-I (in combination with mammogenic hormones) promoted ductal growth in pubertal stage mammary glands cultured in vitro. During postpubertal and pregnancy stages, IGF-II and IGF-IR continued to be expressed in ductal epithelium. Expression of IGF-II in ductal and alveolar epithelium correlated with the pattern of rapidly proliferating cells, as determined by incorporation of 5-Bromo-2'-deoxyuridine, suggesting a potential autocrine or paracrine role for IGF-II as a mitogen for ductal epithelial cells. IGF-I expression was reinitiated in mammary epithelium in the differentiated alveoli at the end of pregnancy, suggesting an additional role for this factor in maintenance of the alveoli during lactation. Taken together, these data support an in vivo role for locally-produced IGFs in promoting ductal growth during puberty and suggest that IGF-I and IGF-II may have distinct functions during pregnancy-induced alveolar development.     

Complexes of the alpha1C and beta subunits generate the necessary signal for membrane targeting of class C L-type calcium channels

In the present study, we investigated the role of channel subunits in the membrane targeting of voltage-dependent L-type calcium channel complexes. We co-expressed the calcium channel pore-forming alpha1C subunit with different accessory beta subunits in HEK-tsA201 cells and examined the subcellular localization of the channel subunits by immunohistochemistry using confocal microscopy and whole-cell radioligand binding studies. While the pore-forming alpha1C subunit exhibited perinuclear staining when expressed alone, and several of the wild-type and mutant beta subunits also exhibited intracellular staining, co-expression of the alpha1C subunit with either the wild-type beta2a subunit, a palmitoylation-deficient beta2a(C3S/C4S) mutant or three other nonpalmitoylated beta isoforms (beta1b, beta3, and beta4 subunits) resulted in the redistribution of both the alpha1C and beta subunits into clusters along the cell surface. Furthermore, the redistribution of calcium channel complexes to the plasma membrane was observed when alpha1C was co-expressed with an N- and C-terminal truncated mutant beta2a containing only the central conserved regions. However, when the alpha1C subunit was co-expressed with an alpha1 beta interaction-deficient mutant, beta2aBID-, we did not observe formation of the channels at the plasma membrane. In addition, an Src homology 3 motif mutant of beta2a that was unable to interact with the alpha1C subunit also failed to target channel complexes to the plasma membrane. Interestingly, co-expression of the pore-forming alpha1C subunit with the largely peripheral accessory alpha2 delta subunit was ineffective in recruiting alpha1C to the plasma membrane, while co-distribution of all three subunits was observed when beta2a was co-expressed with the alpha1C and alpha2 delta subunits. Taken together, our results suggested that the signal necessary for correct plasma membrane targeting of the class C L-type calcium channel complexes is generated as a result of a functional interaction between the alpha1 and beta subunits.