Expect the worse or hope for the best? Prenatal diagnosis of geleophysic dysplasia

Geleophysic dysplasia is a rare, autosomal recessive disorder which causes disproportionate short stature associated with severe physical handicaps, but is compatible with survival into adulthood. We present a case, a first-born child, where genetic counselling difficulties arose following ultrasound recognition of short-limbed dwarfism in association with polyhydramnios and an initial incorrect prenatal diagnosis of lethal chondrodysplasia. After birth of the surviving affected infant, the parents had great difficulty accepting that there had been a prenatal misdiagnosis and they were greatly disappointed by our inability to predict the postnatal survival of an infant to whom no hope of life had previously been given. The correct diagnosis was not made until the proband was nearly 1 year old, and the true prognosis then became clearer. This experience underlines the relative ease of prenatal recognition of skeletal growth abnormalities compared with the considerable difficulties experienced in reaching a precise diagnosis. Thus, following prenatal diagnosis of unspecified chondrodysplasia when parents seek definite information about the prognosis, the temptation to be either overpessimistic or overoptimistic should be avoided.     

Exposure to environmental and mainstream tobacco smoke and risk of spontaneous abortion

The present nationwide, multicenter clinical study was carried out in 26 departments of surgery to define the incidence and attendant mortality of intestinal infarction following abdominal aortic surgery, and to identify patients at risk of it. The data consist of 1752 patients who underwent abdominal aortic reconstruction during 1991-1993 as recorded in the Finnish national vascular registry (FINNVASC). Among the 1752 operations, 27 patients treated at 14 different hospitals had intestinal ischemia, and the complete patient records of all 27 cases were reanalyzed. The incidence of bowel infarction was 1.2%. Among patients operated on for a ruptured aneurysm it was 3.1%, whereas 1.0% of patients with nonruptured aneurysm and 0.6% of those operated on for aortoiliac occlusive disease developed intestinal infarction. In 14 patients (67%) the lesion affected the left colon. The overall 30-day mortality rate was 13% but reached 67% among those with intestinal infarction. We conclude that acute intestinal ischemia with bowel infarction is an infrequent but serious complication of abdominal aortic surgery. It is mainly related to surgery due to aneurysmal disease, and patients with occlusive aortoiliac disease present ischemic complications in the intestines less often. Hypotensive patients being treated for ruptured aneurysm are at greatest risk of intestinal ischemia.     

Catalytic subunit of DNA-dependent protein kinase: impact on lymphocyte development and tumorigenesis

The DNA-dependent protein kinase (DNA-PK) consists of a heterodimer DNA-binding complex, Ku70 and Ku80, and a large catalytic subunit, DNA-PKcs. To examine the role of DNA-PKcs in lymphocyte development, radiation sensitivity, and tumorigenesis, we disrupted the mouse DNA-PKcs by homologous recombination. DNA-PKcs-null mice exhibit neither growth retardation nor a high frequency of T cell lymphoma development, but show severe immunodeficiency and radiation hypersensitivity. In contrast to the Ku70-/- and Ku80-/- phenotype, DNA-PKcs-null mice are blocked for V(D)J coding but not for signal-end joint formation. Furthermore, inactivation of DNA-PKcs leads to hyperplasia and dysplasia of the intestinal mucosa and production of aberrant crypt foci, suggesting a novel role of DNA-PKcs in tumor suppression.     

Enzymatic characteristics of recombinant medium isozyme of 2'-5' oligoadenylate synthetase

P69 is an isozyme of the medium size class of human 2'-5' oligoadenylate synthetases. In this study, recombinant P69 was expressed and used for enzymological and structural investigations. Bacterially expressed P69 was inactive whereas the same protein expressed in insect cells was highly active. Whether this difference could be due to differential post-translational modifications of the protein was investigated. Mutations of appropriate residues showed that myristoylation of the protein was not necessary for enzyme activity. In contrast, inhibition of glycosylation of P69, by tunicamycin treatment of the insect cells, produced an enzymatically inactive protein. Recombinant P69 produced in insect cells was purified by affinity chromatography. It was a dimeric glycoprotein, very stable and completely dependent on double stranded (ds) RNA for activity. The enzyme catalyzed the non-processive synthesis of 2'-5'-linked oligoadenylate products containing up to 30 residues. 2'-O-Methylated dsRNA was incapable of activating P69 and a 25-base pair dsRNA was as effective as larger dsRNA. This expression system will be useful for large scale production of P69 and its mutants for structural studies.     

Quantitation and kinetic properties of hepatic microsomal and recombinant flavin-containing monooxygenases 3 and 5 from humans

For many profoundly hearing-impaired listeners (hearing loss > 90 dB HL) speechreading is the most important means of communication; amplified speech may provide, at best, additional information to speechreading. In order to improve audiovisual communication, three speech pattern elements comprising voice-fundamental frequency (f0), the first formant (F1), and the first and the second formant (F1F2) were presented as supplements to speechreading. A fourth condition consisted of a natural speech supplement, a fifth of speechreading only. Twenty subjects were tested; all audiovisual speech scores were significantly higher than the purely visual scores. Audiovisual scores for amplified, natural speech were significantly higher than those for f0 and F1F2 coded speech. Scores for natural speech and for F1 coded speech were not significantly different. The relations between the increase in audiovisual speech scores over the visual scores and measures of difference limen for frequency (DLf) and gap detection were not clear. The most prominent correlations with the speech scores were found for the DLf at 125 Hz and for gap detection.     

A comparison among different inversion methods for multi-exponential NMR relaxation data

With the object to disclose an association between laryngeal papillomatosis and laryngeal carcinoma, we reviewed 102 patients with laryngeal papillomatosis treated between 1950 and 1979. Seven cases of laryngeal carcinomas were recorded and 1 patient with spread of papilloma to the bronchial tree developed a bronchial carcinoma. The time between onset of papilloma and diagnosis of carcinoma was 4-55 years (mean 24 years). For laryngeal carcinoma the ratio of observed to expected cases was 88. Of the 8 patients developing respiratory tract carcinoma, 2 had received treatment with radiation and 2 had been treated with Bleomycin. Four of these 8 patients were known smokers. This study shows that papillomatosis is more often associated with laryngeal carcinoma than previously reported. It appears, however, that laryngeal papillomas alone seldom induce carcinomas. Apart from irradiation and smoking, Bleomycin could be an important co-factor.