Three germline mutations in the TP53 gene

Three germline mutations in the TP53 tumor-suppressor gene are reported, two of which are not reported previously. A missense mutation at codon 265 of TP53 was found in three patients of a family that complied with the definition of the Li-Fraumeni syndrome. A nonsense mutation in codon 306 was found in a woman who had had a rhabdomyosarcoma at age 4 and a subsequent breast cancer at age 22. She was part of a Li-Fraumeni-like family, but the parental origin of the mutation could not be traced. Finally, while screening for somatic alterations in TP53 in a series of 141 sporadic breast tumors, we detected a constitutional missense mutation in codon 235 in a woman diagnosed with breast cancer at age 26 and a recurrence 4 years later. The recurrence, but not the primary tumor, showed an additional missense mutation at codon 245 as well as loss of the wild-type allele. This suggests that the 245 mutation was particularly important for tumor progression and that there might exist heterogeneity in terms of cancer predisposition potential among the various germline TP53 mutations. Hum Mutat 9:157–163, 1997. © 1997 Wiley-Liss, Inc.     

Evaluation of interleukin-6, tumour necrosis factor-α and interleukin-1β for early diagnosis of neonatal sepsis

The objective of this study was to assess the contribution of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) to an early diagnosis of early-onset neonatal sepsis. A cohort of 117 newborn infants delivered during a 1-y period had IL-6, TNF-alpha and IL-1beta, blood and cerebrospinal fluid (CSF) cultures, leucocyte and platelet count collected on the initial evaluation of possible early-onset sepsis. They were divided into four groups: I, positive blood and/or CSF cultures; II, probably infected with clinical sepsis but negative cultures; III, same as group II but mother received antibiotic antepartum; and IV, newborn infants that did not receive any antibiotic therapy. There were no differences among the four groups with respect to mean gestational ages and birthweights, median Apgar scores, type of delivery, or number of newborn infants with leucocyte count <5000 mm(-3) or >25000 mm(-3), platelet count <100000 mm(-3), immature/total neutrophil ratio >0.2, absolute neutrophil count <1000mm(-3) and median IL-1beta levels. Median IL-6 and TNF-alpha levels were significantly higher in groups with patients with a diagnosis of clinical sepsis than in controls. The optimal cut-off point was 32 pg ml(-1) for IL-6 and 12 pg ml(-1) for TNF-alpha. The combination of both provided a sensitivity of 98.5%. In conclusion, the combination of IL-6 and TNF-alpha is a highly sensitive marker of sepsis in the immediate postnatal period.     

Lithoclast® master in intracorporeal lithotripsy during percutaneous nephrolithotomy: Our experience

Background: This study was carried out to compare the efficacy of Lithoclast® Master with pneumolithotriptor during percutaneous nephrolithotomy (PNL) in the treatment of renal staghorn calculi.     

Multipin solid-phase synthesis of acyl 2,3-diaminopropionic acid oligomers

A modular approach for the synthesis of sets of diverse organic molecules is described. N-α-Fmoc-N-β-Alloc-D-2,3-diaminopropionic acid (Fmoc-D-Dpr(Alloc)-OH) was prepared in four steps from BOC-D-asparagine and used as a scaffold for attachment of sidechains. Using the Multipin approach, a number of model acyl trimers were rapidly prepared by sequential coupling of Fmoc-D-Dpr(Alloc)-OH and acylation of the β-amino group with a range of activated carboxylic acids. © Munksgaard 1996.     

Abnormal phytohemagglutinin-induced T-cell proliferative responses in Hodgkin's disease

Optimal conditions were established for evaluating the phytohemagglutinin-induced proliferative responses of purified peripheral blood T lymphocytes. This assay was utilized to determine whether T cells (in the absence of monocytes and serum inhibitory factors) from patients with Hodgkin's disease were defective in their ability to proliferative in response to optimal (50 microgram/ml) and suboptimal (25 and 12.5 microgram/ml) concentrations of phytohemagglutinin. T cells from 6 of 12 untreated patients exhibited 6- day proliferative responses below the range of 15 control subjects using optimal mitogen concentrations, and 9 of 12 patients exhibited subnormal responses using lower concentrations. Kinetic analyses indicated that the abnormal T-cell proliferative responses were characterized by peak proliferation occurring at day 4 or 5, rather than day 6. The observed abnormalities were not related to elevations in the proportions of T cells bearing surface receptors for IgG (T gamma Cells). Our results suggest that intrinsic functional T-cell defects contribute to the impaired immunity associated with Hodgkin's disease.     

Primary hyperparathyroidism in a child. Use of jugular venous catheterization in diagnosis

A 10-year-old boy with a parathyroid ademona is reported. Parathyroid hormone estimations of samples obtained by selective jugular venous catheterization were useful in diagnosis and for localizing the tumour before operation.