Human papillomavirus investigation of patients with cervical intraepithelial neoplasia 3, some of whom progressed to invasive cancer

Unstable expansion of the CTG repeats in the 3' untranslated region encoding a member of the protein kinase family in the q13.3 band on chromosome 19 is a mutation specific for myotonic dystrophy. To examine the correlation between clinical expression and CTG trinucleotide repeat length, we carried out Southern blot analysis in a family with myotonic dystrophy. In this pedigree, the expanded CTG repeats were transmitted maternally. The mother had three female children. The mother had about 200 CTG repeats, and the number of repeats for each child was about 800, 1500 and 1600 in birth order. The mother and the patient with 800 repeats were unaware of muscle weakness or myotonia. Symptoms were present from age 3 years in the patient with 1500 repeats and from birth in the one with 1600 repeats. Although the mother menstruated regularly, the patients with 800 and 1500 repeats both menstruated irregularly, and the one with 1600 repeats has never menstruated. The age of onset and severity of the disease were correlated with the size of the expanded repeats. Endocrinological studies revealed that the basal levels of the gonadotropins, PRL and E2 were within normal range, and a pituitary response to LHRH was observed. These data suggest that the amenorrhea and menstrual irregularities were caused by a suprahypophyseal dysfunction. When expanded CTG repeats are transmitted maternally, abnormal products resulting from the metabolic disturbance in the affected mother may harm the fetus in utero. A heterozygous fetus, who has more CTG repeats, may be unable to metabolize the pathologic products sufficiently and therefore may become more severely affected. This may explain the exclusive maternal transmission of congenital myotonic dystrophy.     

Rat and human pancreatic islet cells contain a calcium ion independent phospholipase A2 activity selective for hydrolysis of arachidonate which is stimulated by adenosine triphosphate and is specifically localized to islet beta-cells

The recent demonstration that myocardial Ca(2+)-independent phospholipase A2 exists as a complex of catalytic and regulatory polypeptides that is modulated by ATP has suggested a novel mechanisms through which alterations in glycolytic flux can be coupled to the generation of eicosanoids which facilitate insulin secretion. To determine the potential relevance of this mechanism, we examined the kinetic characteristics, substrate specificities, and cellular locus of phospholipase A2 activity in pancreatic islets. Rat pancreatic islets contain a Ca(2+)-independent phospholipase A2 activity which is optimal at physiologic pH, preferentially hydrolyzes phospholipid substrates containing a vinyl ether linkage at the sn-1 position, and prefers arachidonic acid compared to oleic acid in the sn-2 position. Rat islet Ca(2+)-independent phospholipase A2 activity is inhibited by the mechanism-based inhibitor (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one and is stimulated by ATP. Purification of beta-cells from dispersed pancreatic islet cells by fluorescence-activated cell sorting demonstrated that beta-cells (but not non-beta-cells) contain Ca(2+)-independent, ATP-stimulated phospholipase A2 activity. Remarkably, clonal RIN-m5f insulinoma cells, which possess a defect in glucose-induced insulin secretion, contain a Ca(2+)-independent phospholipase A2 which is not modulated by alterations in ATP concentration. Collectively, these results and those of an accompanying paper [Ramanadham et al. (1993) Biochemistry (following paper in this issue)] implicate Ca(2+)-independent phospholipase A2 as a putative glucose sensor which can couple alterations in glycolytic metabolism to the generation of biologically active eicosanoids and thereby facilitate glucose-induced insulin secretion.     

Routine microbiological testing in sudden and unexpected infant death

We reviewed 187 depth recorded seizures in 33 patients with non-lesional temporal lobe complex partial seizures. All patients had a minimum of 1 year follow-up following temporal lobectomy. We classified seizure onset pattern as rhythmic activity, attenuation, or repetitive spikes or spike wave complexes. The most common pattern of seizure onset was rhythmic activity and the next most common pattern was repetitive spikes. Seventy-five seizures (49%) had only one seizure onset pattern, and 79 seizures (51%) had a combination of seizure onset patterns. The degree of hippocampal gliosis strongly predicted the type of seizure onset pattern (Chi square = 24.07, 2 d.f., P < 0.01). The rhythmic activity pattern was associated with mild gliosis, and the repetitive spike pattern was associated with severe gliosis. We classified seizure onset as focal or regional based on the number of electrode contacts that were involved by the ictal EEG. A focal seizure onset was associated with an excellent outcome following temporal lobectomy.     

Deletions in one domain of the Friend virus-encoded membrane glycoprotein overcome host range restrictions for erythroleukemia

Although the Friend virus-encoded membrane glycoprotein (gp55) activates erythropoietin receptors (EpoR) to cause erythroblastosis only in certain inbred strains of mice but not in other species, mutant viruses can overcome aspects of mouse resistance. Thus, mice homozygous for the resistance allele of the Fv-2 gene are unaffected by gp55 but are susceptible to mutant glycoproteins that have partial deletions in their ecotropic domains. These and other results have suggested that proteins coded for by polymorphic Fv-2 alleles might directly or indirectly interact with EpoR and that changes in gp55 can overcome this defense. A new viral mutant with an exceptionally large deletion in its ecotropic domain is now also shown to overcome Fv-2rr resistance. In all cases, the glycoproteins that activate EpoR are processed to cell surfaces as disulfide-bonded dimers. To initiate analysis of nonmurine resistances, we expressed human EpoR and mouse EpoR in the interleukin 3-dependent mouse cell line BaF3 and compared the abilities of Friend virus-encoded glycoproteins to convert these cells to growth factor independence. Human EpoR was activated in these cells by erythropoietin but was resistant to gp55. However, human EpoR was efficiently activated in these cells by the same viral mutants that overcome Fv-2rr resistance in mice. By construction and analysis of human-mouse EpoR chimeras, we obtained evidence that the cytosolic domain of human EpoR contributes to its resistance to gp55 and that this resistance is mediated by accessory cellular factors. Aspects of host resistance in both murine and nonmurine species are targeted specifically against the ecotropic domain of gp55.     

Biliary obstruction due to duodenojejunal intussusception in Peutz-Jeghers syndrome

We reported an operative case of bilateral coronary artery fistulae to pulmonary artery associated with a giant saccular aneurysm, the largest of which measured 30 x 30 mm. The patient was a 75 year old female who had anginal pain due to coronary steal phenomenon. A continuous murmur was detected. After establishing total cardiopulmonary bypass, two distal orifices of the fistula connected to the main pulmonary artery were closed with 5-0 polypropylene plegeted sutures. Aneurysmorrhaphy was then performed for giant saccular aneurysm. Postoperative course was uneventful.     

Phenomenological aspects of a modified fragmentation test using small quantities of explosive

This paper describes the phenomenological aspects of a modified fragmentation test which utilizes an annulus of high explosive in contact with the inner wall of a cylinder of material under test. The shock interactions within the cylinder wall on detonation of the explosive are modelled using a one-dimensional Lagrangian computer code. Predictions of fragment velocities are made in this work. The velocities are found to be influenced by the spallation of the cylinder and this effect can be accounted for in the model by using the position of the spall surfaces which have been obtained from experimental firings of cylinders.

The fragment velocities are found to be much lower than those predicted for a conventional fragmentation test which utilizes a cylinder completely filled with high explosive and this suggests that the post-fragmentation damage of the fragments on recovery from the modified fragmentation test will be small. Experimental evidence from the steel cylinders tested in this work shows that the fragmentation mechanisms operating at the initiation of the test are similar to those reported for a conventional fragmentation test.