Molecular genetic changes found in human lung cancer and its precursor lesions.
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Biomedical subjects
Publications and source records attributed to S Bader.
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MOD cavities in 60 endodontically treated teeth were restored using six different methods. Copper rings were filled with commercial hard-setting cement and the teeth were placed up to the level of the cemento-enamel junction. The teeth were grouped according to restorative method, mounted in an Instron TT machine, and the buccal walls subjected to a slowly increasing compressive force until fracture occurred. The force of fracture of the walls of each tooth was recorded and the results in the various groups compared. All teeth fractured in a similar manner irrespective of the restorative method used. All groups restored with the newer bonding system had higher resistance to fracture than those restored with an acid etch chemically cured composite resin technique. The groups restored with Den-Mat Tenure Core Paste or a Variglass VLC base and Prisma APH were significantly stronger than the acid etch Concise restored teeth (P < 0.05). No statistically significant differences were found between the other groups (P > 0.05).
The deletion of the short arm of chromosome 3 is frequently observed in lung cancer. To determine whether the von Hippel-Lindau (VHL) disease tumor suppressor gene located at 3p25 is responsible for oncogenesis in lung cancer, we searched the known open reading frame using the single-strand conformation polymorphism (SSCP) technique for mutations in the VHL gene in 72 cancer cell lines including small cell (SCLC) and non-small cell (NSCLC) lung cancers, carcinoids, and mesotheliomas. SSCP analysis showed that four cell lines have altered SSCP patterns within the coding region and one in an intron of the VHL gene. SCLC line NCI-H1672 had a somatic mutation, G to A at nucleotide (nt) 530, leading to amino acid substitution (glycine to aspartic acid) compared to normal DNA from the same patient. Mesothelioma line NCI-H28 had T to A mutation at nt 479 leading to leucine to histidine amino acid change. We found one frequent polymorphism A (0.72) or G (0.28) at nt 19 resulting in either serine or glycine at this position, changes also found in normal peripheral blood cell DNA, often in a heterozygous state. In addition, we found single rare polymorphisms which did not alter the coding region including: C to G at nt 396, G to T at nt 843, and C to T change in an intron. These results suggest that the VHL gene is only rarely mutated in thoracic malignancies.
Cytogenetic analyses of non-small cell lung cancer have revealed deletions of the short arm of chromosome 9 with breakpoints at 9p11-pter in a significant proportion of tumors. Recent evidence suggests that homozygous loss of the interferon (IFN) and methylthioadenosine phosphorylase (MTAP) genes located on 9p and a tumor suppressor gene closely linked to them is associated with acute lymphoblastic leukemia and with gliomas. We have observed alterations of DNA sequences on 9p which include the IFN genes at a significant frequency in all types of human lung cancers (20 of 56 or 36%). The genetic alterations observed include homozygous or hemizygous deletions of the IFN genes as well as rearrangement of contiguous DNA sequences. In addition to these genomic alterations, 10 of 22 (45%) cell lines examined lacked MTAP enzyme activity. Overall, 24 of 56 (43%) lung cancer cell lines examined had hemizygous or homozygous loss of DNA sequences which include the IFN or MTAP genes. These findings suggest that the putative tumor suppressor gene at this locus contributes to the malignant process in lung cancers, as well as other types of human cancer.
Removal of ipsilateral entorhinal afferents to the fascia dentata results in a retraction of postsynaptic parvalbumin (PARV)-containing dendrites of GABAergic neurons from the outer molecular layer. This study analyzes the reorganization of input synapses of these identified neurons following deafferentation. The density of synaptic input (total length of synaptic membrane specializations) of PARV-immunostained dendrites increased by 34% in the outer molecular layer of the fascia dentata 8 days, and by 21% 55 days following lesion when compared with unoperated controls. Eight days postlesion this increase was mainly due to an enlargement of synaptic membrane specializations of single terminals whereas 55 days after the lesion there was an increase in the number of synapses on the identified dendrites. Our results suggest expansion of terminals of remaining afferent systems (i.e. commissural fibers) in the early postlesional period and reactive synaptogenesis (i.e. de novo formation of synaptic contacts) on PARV-positive dendrites after long survival time. This increased innervation may be of functional importance as it might compensate for the reduction of the receptive field of the PARV-positive, supposedly inhibitory neurons in the postlesional dentate gyrus.
The spontaneous hypertensive rat is an animal model characterized by a syndrome of hypertension, insulin resistance and hyperinsulinaemia. To elucidate whether in analogy to other insulin resistant animal models an inactivity of the insulin receptor kinase or an alteration of the glucose transporter (GLUT 4) level in the skeletal muscle might contribute to the pathogenesis of insulin resistance we determined insulin receptor kinase activity and GLUT 4 level in the hindlimbs of spontaneous hypertensive rats and normotensive control rats. Normotensive normoinsulinaemic Lewis and Wistar rats were used as insulin sensitive controls, obese Zucker rats were used as an insulin resistant control with known reduced skeletal muscle insulin receptor kinase activity. Binding of 125I-insulin, crosslinking of 125I-B26-insulin, autophosphorylation in vitro with 32P-ATP and phosphorylation of the synthetic substrate Poly (Glu 4: Tyr 1) were performed after partial purification of solubilized receptors on wheat germ agglutinin columns. GLUT 4 levels were determined by Western blotting of subcellular muscle membranes. Insulin receptors from spontaneous hypertensive rats compared to those from Lewis and Wistar rats showed no difference of the binding characteristics or the in vitro auto- and substrate phosphorylation activity of the receptor, while in the Zucker rats the earlier described insulin receptor kinase defect was clearly evident. Western blots of subcellular muscle membrane fractions with antibodies against GLUT 4 revealed no difference in transporter levels. These data suggest that insulin resistance in spontaneous hypertensive rats is caused neither by an insulin receptor inactivity nor by a decreased number of glucose transporters in the skeletal muscle.
Incidence and type of cardiac complications in 701 patients undergoing arterial vascular surgery were prospectively investigated to identify high-risk groups. Cardiac morbidity was 10.1%. Cardiac complications were responsible for 28 deaths (57%). Using logistic regression analysis, age (cardiac morbidity greater than 7017.3%), impaired renal function (19.8%), and congestive heart failure (17.3%) were the main independent risk factors. In addition, 4 risk factors (arrhythmia, coronary artery disease, anemia, emergency surgery) showed significant individual association with cardiac complications. Cardiac morbidity increased to 27.8% in patients with more than 2 of these 7 risk factors. A further association could be demonstrated between the degree of peripheral vascular disease and cardiac morbidity, but not with the extent of the operation. Based on our results a distinction between three groups of different cardiac risk can be made. A clinical algorithm for further cardiac assessment in high-risk patients is presented.
This paper describes a national study to determine levels and kinds of videodisc utilization in health science institutions throughout North America. In the winter of 1989, 922 surveys were mailed to six different health science professional groups; 244 (26%) completed survey forms were returned. A comparison between this survey and one conducted by the authors in 1987 clearly shows that videodisc technology for medical education is varied and expanding within academic health science centers in North America.
This paper describes a national survey designed to determine trends in videodisc use, development, and production in academic health sciences libraries throughout North America. In the winter of 1989, 131 four-page survey instruments went to library directors in academic health sciences institutions. Of these, 63 (48%) survey forms were completed and returned. Survey results indicated a wide range of videodisc technology use and development and a growing production of both Level I and Level III videodiscs within academic health sciences libraries. Videodisc technology delivery for student use was centralized within many medical libraries, although videodisc development was not centralized within academic health sciences centers. Most libraries (67%) have purchased videodisc technology and over one fourth (28%) are repurposing a videodisc within their institution. Over one fourth (25%) of respondents have already begun to develop their own videodisc software, and almost one fourth (24%) of respondents have a Level III videodisc in production. Clearly the use and development of videodisc technology for biomedical instruction is expanding within academic health sciences libraries.
This paper describes a national survey designed to determine trends in videodisc utilization in academic health science centers throughout North America. In the fall of 1986, we mailed 1,449 four-page survey instruments to five different professional groups within health science institutions. Of those surveys, 247 (17%) were completed and returned. Survey results indicate a wide range of videodisc technology utilization. The role of interactive video technology for biomedical instruction is clearly expanding.
Microcomputers, and a new generation of on-line systems designed for the end-user, now make it possible for physicians to search MEDLINE and a variety of other databases in the convenience of their offices or homes. This article explains some basics of online searching, describes capabilities and options to consider when selecting a system, and identifies hardware and software needed to adapt a micro for online searching. A chart comparing system features and costs, and providing information on where to go for more information is also included.
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Light-induced phosphorylation of rhodopsin has been extensively studied by a number of investigators from a biochemical point of view. However, little is known about the physiological function of this reaction. The slow rates measured for phosphorylation and dephosphorylation suggest that it may be involved in visual adaptation rather than in excitation. This paper presents biochemical data obtained from phosphorylation experiments in isolated photoreceptor membranes as well as in the physiological system of whole retinas and living animals. An attempt is made to compare the phosphorylation reaction with visual adaptation hypotheses taken from the electrophysiological literature. Finally, effects of cyclic nucleotide metabolism on the sensitivity of photoreceptors are presented and discussed.
Phosphorylation of rhodopsin has been measured in isolated retinas incubated with 32P-phosphate under physiological conditions. The half-time of the light-induced phosphorylation was found to be approximately 2 min with frog retinas at 21 degrees C, and in the order of 1--2 min with cattle retinas at 36 degrees C. It is suggested by this slow rate that the phosphorylation reaction is not directly involved in the chain of events which lead from absorption of a photon to excitation of the photoreceptor cells but may perhaps have a regulatory function in controlling light/dark adaptation.
From 1978 to 1987, 139 children were treated for osteomyelitis at our institution, among them 6 with osteomyelitis of the clavicle. All six patients presented with a primary chronic osteomyelitis. Three children sustained a trauma anamnestically. Pathohistological examinations revealed a chronic, unspecific inflammation in all cases. Immobilisation was achieved by means of a DESAULT-cast or an abduction splint for 7 to 36 weeks, antibiotics (clindamycin) were given for 6 to 55 weeks, starting with intravenous administration for 1 weeks maximally. All patients were primarily operated on, mostly undergoing curettage of affected regions or partial resection. After 4 to 10 years, 4 children are well and without evidence of recurrence, 2 children are still under treatment for recurrences.