Quantitative MRI studies for assessment of multiple sclerosis.

Although magnetic resonance imaging (MRI) is a valuable aid in the initial diagnosis of multiple sclerosis (MS), quantitatively MRI has been disappointing in staging and evaluating therapy protocols by means of serial examinations. In this study, image processing algorithms were developed for the global analysis of MR images of the cerebrum. Limited three-dimensional segmentation was achieved through histogram analysis by these algorithms, which are essentially operator independent. The effects of coil response and tip angles, patient positioning, and interslice gap thicknesses were examined for 10 MS patients with repeated examinations for a total of 72 images. Effects of technique and instrumentation errors were approximately 6%, and agreement between two independent operators for measuring the total MR pixel sum from periventricular effusions and intense MS plaques was better than 97% with a standard deviation of 2.9%.     

Mutations of the human thyrotropin-beta subunit glycosylation site reduce thyrotropin synthesis independent of changes in glycosylation status.

In recent studies, site-directed mutagenesis has been used to alter the tripeptide glycosylation recognition sequences of glycoprotein hormone subunits, thereby affecting their structure and function. However, it is not known whether these effects result from changes in glycosylation status, amino acid sequence, or both. We therefore studied the synthesis of wild-type and mutant recombinant human thyrotropins produced by transient transfection of a human cell line. Mutating the TSH-beta subunit glycosylation recognition sequence, Asn-Thr-Thr (codons 23-25), to either Gln-Thr-Thr or Asn-Thr-Tyr abolished subunit glycosylation, as demonstrated by the inability to incorporate 3H-carbohydrates. However, a third mutation (Asn-Thr-Ser) contained an intact glycosylation recognition sequence site, and was shown to retain glycosylation. The mutations that abolished TSH-beta subunit glycosylation resulted in greater than 90% decreases in TSH synthesis. However, the glycosylation recognition sequence mutant that retained beta subunit glycosylation exhibited a 70% decrease in TSH production. These decreases were not attributable to the intracellular accumulation of TSH or its free beta subunit. We also engineered two TSH-beta subunit mutations that did not alter the glycosylation recognition sequence. A glycine to arginine mutation adjacent to the glycosylation recognition sequence, in a region thought to be critical for heterodimer formation, abolished TSH production. In contrast, shortening the TSH-beta subunit carboxyterminus by six amino acids increased TSH synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Locoregional chemotherapy in the treatment of liver metastasis of breast carcinoma]

Locoregional chemotherapy enables specific treatment of organ metastases by using a dosage of medication that is maximally effective but only has minimal side effects on other organs. Since 1983, we have applied this procedure in patients whose liver represented the only target-organ of metastases. Between 1983 and 1990, locoregional chemotherapy was performed in 59 women suffering from liver metastases of breast cancer. The average age of our patients was 52 years. 4 patients were treated for solitary metastases that could not be resected, in 5 patients the infiltration of hepatic parenchyma with metastases accounted to 25%, in 32 patients hepatic infiltration ranged between 25% and 75% and in 18 patients it surpassed 75%. In 39% of our patients, a partial remission occurred. The mean period of survival after beginning of treatment was 149 days, whereas the longest survival time lasted 1009 days. We conclude that the locoregional chemotherapy, destined for treatment of liver-metastases of breast cancer, with a mean survival time of only five months could insufficiently satisfy our expectations. Therefore, a decision to administer such palliative therapy should be made on an individual basis. In our opinion, one indication represents solitary metastases that are not resectable, a further indication is pain due to expansion of the liver capsule because of diffuse metastases.     

Substance abuse in pregnancy: teratogenesis

Substances of abuse include those that are legal (such as alcohol) and those that are illegal (street drugs). Many of these agents produce reproductive toxicity including intrauterine growth retardation. Teratogenesis is unproven with most of these agents. Alcohol is an exception, producing the fetal alcohol syndrome. Cocaine causes marked reproductive toxicity including decreased growth and morbidity. A number of birth defects have been associated with cocaine use including genitourinary, cardiac, and limb anomalies. The reproductive toxic and putative teratogenic effects of cocaine are probably associated with its well-known pharmacologic action causing vasoconstriction. From preliminary studies, it would appear that methamphetamine also produces reproductive toxic effects similar to those of cocaine.     

MRI and CT in Krabbe's disease: case report

A case of infantile Krabbe's disease was first recognised as areas of relatively increased density on CT in the thalamus lateral geniculate body and dentate nucleus. These sites were subsequently shown on MRI to have a paramagnetic effect, being characterised by short T2 and T1. Subsequent examinations showed development of atrophy and high signal in white matter.     

Multiplex PCR analysis of in vivo-arising deletion mutations in the hprt gene of human T-lymphocytes

A multiplex polymerase chain reaction (PCR) procedure was adapted for the rapid and efficient evaluation of deletions of the hypoxanthine guanine phosphoribosyltransferase (hprt) gene in human T-lymphocytes. The hprt clonal assay was used to isolate in vivo-arising hprt-deficient T-cells from six healthy males. Mutant frequencies ranged from 9-27 × 10^?6. Simple crude cellular extracts from 223 mutants were analyzed for hprt gene deletion. Sixteen (7.2%) were found to be due to total gene deletion and 22 (9.9%) were due to partial gene deletion. The relatively high frequency of total gene deletions was caused by replicate isolates of a single mutational event as shown by single-strand conformation polymorphism (SSCP) analysis of rearranged T-cell receptor (TCR)-γ genes. Eighteen of the 22 partial hprt gene deletion mutants were determined to be of independent origin based on a unique hprt mutation or SSCP-TCR-γ pattern. One-half (9/18) of the partial deletion mutants involved all or part of exon 4 alone, suggesting that this region of the hprt gene is prone to deletion. The small deletions effecting exon 1 (1 mutant), exon 2 (2 mutants), and exon 4 (6 mutants) would not have been detected by conventional Southern blot analysis and may represent a new, previously unrecognized class of mutations. The ready isolation of such intragenic deletions will allow the characterization of breakpoint junctions and may provide insights into the important processes of DNA breakage and rejoining. © 1994 Wiley-Liss, Inc.     

Current perspectives on septic shock

Although septic shock may be initiated by invading microbes, it is the metabolic and immunologic host responses that determine the true pathophysiology of this common critical care illness. Currently, septic shock therapeutics emphasize empiric and symptomatic treatment. Biochemical elucidation of the septic process will ultimately result in specific interventions for this ominous intensive care syndrome.