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1.
Bone Joint J ; 99-B(2): 255-260, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28148670

ABSTRACT

AIMS: To analyse the influence of upper extremity trauma on the long-term outcome of polytraumatised patients. PATIENTS AND METHODS: A total of 629 multiply injured patients were included in a follow-up study at least ten years after injury (mean age 26.5 years, standard deviation 12.4). The extent of the patients' injury was classified using the Injury Severity Score. Outcome was measured using the Hannover Score for Polytrauma Outcome (HASPOC), Short Form (SF)-12, rehabilitation duration, and employment status. Outcomes for patients with and without a fracture of the upper extremity were compared and analysed with regard to specific fracture regions and any additional brachial plexus lesion. RESULTS: In all, 307 multiply-injured patients with and 322 without upper extremity injuries were included in the study. The groups with and without upper limb injuries were similar with respect to demographic data and injury pattern, except for midface trauma. There were no significant differences in the long-term outcome. In patients with brachial plexus lesions there were significantly more who were unemployed, required greater retraining and a worse HASPOC. CONCLUSION: Injuries to the upper extremities seem to have limited effect on long-term outcome in patients with polytrauma, as long as no injury was caused to the brachial plexus. Cite this article: Bone Joint J 2017;99-B:255-60.


Subject(s)
Arm Injuries/rehabilitation , Brachial Plexus Neuropathies/rehabilitation , Brachial Plexus/injuries , Fractures, Bone/rehabilitation , Multiple Trauma/rehabilitation , Shoulder Injuries/rehabilitation , Upper Extremity/injuries , Adolescent , Adult , Brachial Plexus Neuropathies/etiology , Child , Child, Preschool , Cohort Studies , Female , Follow-Up Studies , Humans , Injury Severity Score , Male , Middle Aged , Multiple Trauma/therapy , Social Conditions , Time Factors , Treatment Outcome , Young Adult
2.
Bone Joint J ; 95-B(4): 548-53, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23539709

ABSTRACT

We report the functional and socioeconomic long-term outcome of patients with pelvic ring injuries. We identified 109 patients treated at a Level I trauma centre between 1973 and 1990 with multiple blunt orthopaedic injuries including an injury to the pelvic ring, with an Injury Severity Score (ISS) of ≥ 16. These patients were invited for clinical review at a minimum of ten years after the initial injury, at which point functional results, general health scores and socioeconomic factors were assessed. In all 33 isolated anterior (group A), 33 isolated posterior (group P) and 43 combined anterior/posterior pelvic ring injuries (group A/P) were included. The mean age of the patients at injury was 28.8 years (5 to 55) and the mean ISS was 22.7 (16 to 44). At review the mean Short-Form 12 physical component score for the A/P group was 38.71 (22.12 to 56.56) and the mean Hannover Score for Polytrauma Outcome subjective score was 67.27 (12.48 to 147.42), being significantly worse compared with the other two groups (p = 0.004 and p = 0.024, respectively). A total of 42 patients (39%) had a limp and 12 (11%) required crutches. Car or public transport usage was restricted in 16 patients (15%). Overall patients in groups P and A/P had a worse outcome. The long-term outcome of patients with posterior or combined anterior/posterior pelvic ring injuries is poorer than of those with an isolated anterior injury.


Subject(s)
Fractures, Bone/surgery , Pelvic Bones/injuries , Pelvic Bones/surgery , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Male , Middle Aged , Time Factors , Treatment Outcome , Young Adult
3.
Unfallchirurg ; 116(6): 553-8, 2013 Jun.
Article in German | MEDLINE | ID: mdl-23052700

ABSTRACT

The appropriate treatment of a distal tibia fracture in multimorbid patients with poor soft tissue and skin conditions, poor peripheral blood supply and osteopenic bone is challenging. In this case report we present two patients with these characteristics. Given these exceptional conditions none of the conventional therapies (e.g. cast, internal plate fixation, external fixation, anterograde intramedullary nailing) appeared feasible. To achieve sufficient fracture healing, we chose an unconventional treatment approach of retrograde tibial nailing with inclusion of the ankle and subtalar joint.


Subject(s)
Ankle Fractures , Fracture Fixation, Intramedullary/instrumentation , Fracture Fixation, Intramedullary/methods , Soft Tissue Injuries/complications , Soft Tissue Injuries/surgery , Tibial Fractures/complications , Tibial Fractures/surgery , Aged , Aged, 80 and over , Female , Humans , Treatment Outcome
4.
Unfallchirurg ; 110(3): 235-42; quiz 243, 2007 Mar.
Article in German | MEDLINE | ID: mdl-17333063

ABSTRACT

In polytraumatized patients severe joint injuries represent a special entity because their management is complex and lengthy. The surgeon must decide if limb salvage is indicated and which further surgical steps have to be instituted. The decision for amputation is based on the patient's general condition and the soft-tissue and neurovascular injury. Scoring systems are useful for decision making. Limb salvage is associated with a multistage surgical approach. Priority is given to restoration of sufficient blood supply and soft tissue repair; the indication for fasciotomy covers a wide field. To avoid further compromise to soft tissue and perfusion, temporary joint and fracture stabilization is required. Definitive surgery has to be delayed until the 2 week period, starting between the fifth and tenth day after trauma.


Subject(s)
Knee Injuries/surgery , Multiple Trauma/surgery , Adult , Amputation, Surgical , Angiography , External Fixators , Female , Humans , Ischemia/diagnosis , Ischemia/surgery , Joint Dislocations/diagnosis , Joint Dislocations/surgery , Knee/blood supply , Knee Injuries/diagnosis , Limb Salvage , Male , Middle Aged , Multiple Trauma/diagnosis , Prognosis , Recovery of Function/physiology , Reoperation , Soft Tissue Injuries/diagnosis , Soft Tissue Injuries/surgery , Trauma Severity Indices
5.
Injury ; 37(12): 1197-203, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17087960

ABSTRACT

INTRODUCTION: There is limited information available about the long-term follow-up of polytrauma patients. In this study, the social and medical sequelae of trauma were reinvestigated at 10 years after the injury. METHODS: Patients were selected out of a population of polytraumatised patients treated at Hannover Medical School between 1973 and 1990. INCLUSION CRITERIA: multiple injuries treated at one institution, age between 3 and 60 years of age at the time of injury. Patients were recruited by gathering their residences from the charts. If patients had moved, up to three different registration offices were contacted by mail. The patient was contacted by mail (maximum three times) and by telephone. A patient was documented as lost to follow-up if none of these attempts was successful, or if he did not fulfil three subsequent appointments. All patients were examined by a physician, using a patient questionnaire and a standardized physical exam. RESULTS: Six hundred thirty-seven patients (67.8% of the potential enrollees) were evaluated on an outpatient basis by a trauma surgeon using a self-administered patient questionnaire and a standardized physical exam. In these, the average follow-up was 17.5 (range 10-28) years; the average Injury Severity Score (ISS) was 20.7 (range 4-54). Head injuries were the third most frequent injuries, but represented the most frequent cause of permanent disability (40%). The overall rehabilitation status graded by the patients was very good in 14.1%, good in 33.0%, satisfactory in 29.3%, sufficient in 16.0% and poor or insufficient in 7.5%. CONCLUSIONS: This study suggests that a high percentage of patients can be recruited for follow-up even after 10 years post trauma with the use of a meticulous reinvitation strategy. Head injuries accounted for the most frequent cause of disability, suggesting that more research should be provided to minimise the degree of injury and improve the outcome for head injured patients. Subjective grading of the outcome was better than expected in patients who had regained complete social rehabilitation.


Subject(s)
Craniocerebral Trauma/surgery , Femoral Neck Fractures/surgery , Multiple Trauma/surgery , Pelvic Bones/injuries , Adolescent , Adult , Child , Child, Preschool , Craniocerebral Trauma/rehabilitation , Female , Femoral Neck Fractures/rehabilitation , Follow-Up Studies , Humans , Injury Severity Score , Male , Middle Aged , Multiple Trauma/rehabilitation , Pelvic Bones/surgery , Surveys and Questionnaires , Time Factors , Trauma Centers , Treatment Outcome
6.
Knee Surg Sports Traumatol Arthrosc ; 14(9): 865-8, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16479410

ABSTRACT

Poly-L: -lactic acid biodegradable screws have been used effectively for graft fixation in anterior cruciate ligament (ACL) reconstruction. The overall complication rate associated with the use of this implant is low, although some authors reported complications, such as osteolysis and aseptic effusion of the knee joint. We report a case of a 29-year-old female patient with a failure of a biodegradable interference screw at 22 months after ACL reconstruction using bone-patellar tendon-bone graft. In this illustrated case, the screw broke and migrated into the knee joint. In addition, we performed a detailed review of the medical literature from 1990-2005 to identify possible causes of biodegradable screw failures. We identified six published cases of bioabsorbable interference screw failure with migration into the knee joint. Several authors have reported small diameter of the screw, poor bone quality, bone resorption, and screw divergence as potential causes for intraarticular migration of metallic interference screws. With regard to bioscrews, no specific risk factors for screw breakage and intraarticular migration have been reported. ACL reconstruction with the use of bioabsorbable interference screws for fixation is considered to be reliable. However, we need to be aware of potential problems associated with the use of this implant. Early recognition of bioscrew failure may prevent associated morbidities, such as subsequent cartilage damage.


Subject(s)
Absorbable Implants , Anterior Cruciate Ligament/surgery , Bone Screws , Foreign-Body Migration/surgery , Adult , Anterior Cruciate Ligament Injuries , Arthroscopy , Bone-Patellar Tendon-Bone Grafting , Female , Humans , Lactic Acid , Polyesters , Polymers , Prosthesis Failure
7.
Injury ; 36(1): 169-77, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15589937

ABSTRACT

Previous studies have suggested that the lower-extremities are among the most frequently injured body regions in polytrauma patients and have a major impact on the functional recovery following polytrauma. In particular, injuries to the distal part of the lower-extremity appear to be associated with a poor functional outcome. Therefore, the goal of this study was to evaluate the impact of injuries below the knee joint on the long-term functional outcome following polytrauma. Three hundred eighty-nine polytrauma patients with associated lower-extremity fractures and a minimum follow-up of 10 years were included in this study. All patients were examined by a doctor, using a patient questionnaire and a standardised physical examination. Significantly, inferior outcomes were seen in patients with fractures below the knee joint as measured by the modified Karlström-Olerud score, Lysholm score, range of motion, weight bearing status, Hannover score for polytrauma outcome (HASPOC), SF-12, Tegner activity score, and inability to work (P < 0.05). Fractures below the knee joint have a significant impact on the functional recovery following polytrauma. We suggest that delayed treatment, thin soft tissue envelope below the knee joint, high-energy trauma, unfavorable blood supply, and complex fracture patterns contribute to these unfavorable outcomes.


Subject(s)
Fractures, Bone/surgery , Leg Injuries/physiopathology , Multiple Trauma/physiopathology , Adult , Female , Follow-Up Studies , Gait/physiology , Humans , Knee Joint , Leg Injuries/pathology , Male , Multiple Trauma/pathology , Odds Ratio , Pain Measurement , Prognosis , Range of Motion, Articular/physiology , Recovery of Function , Treatment Outcome , Weight-Bearing/physiology
8.
Int Orthop ; 28(4): 244-51, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15103503

ABSTRACT

During a 6-year period, 177 patients with a displaced sacral fracture were treated at our level-one trauma centre. At the initial presentation, 13 patients demonstrated a neurological deficit as a result of their sacral fracture. Six patients underwent surgical decompression, and seven patients were managed without surgical decompression. All patients were re-assessed at an average follow-up of 27.1 (range 12-84) months using the modified SOFCOT Index and the SF-36. Patients undergoing surgical decompression had a significantly better neurological improvement as measured by the modified SOFCOT Index (p=0.014). Moreover, patients undergoing surgical decompression had a significantly better physical function than the patients that were managed without surgical decompression, as measured by the SF-36 (p=0.044). We therefore believe that patients undergoing surgical decompression achieve better neurological improvement and better functional results.


Subject(s)
Decompression, Surgical , Sacrum , Spinal Cord Compression/etiology , Spinal Cord Compression/surgery , Spinal Fractures/complications , Spinal Fractures/surgery , Adolescent , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Radiography , Spinal Fractures/diagnostic imaging , Statistics, Nonparametric , Treatment Outcome
9.
Unfallchirurg ; 107(3): 239-43, 2004 Mar.
Article in German | MEDLINE | ID: mdl-15045201

ABSTRACT

Open reduction and internal fixation is the treatment of choice for displaced acetabular fractures. The surgical approach depends on the fracture type, concomitant injuries, and general condition of the patient. The ilioinguinal approach provides a good exposure to the medial wall and is associated with an acceptable degree of surgical trauma. Exposure of the joint surface, however, is difficult when using the ilioinguinal approach. We report a case of a polytraumatized 39-year-old patient who sustained a posterior hip displacement and a two-column acetabular fracture. An osteotomy of the iliac ala was performed via an ilioinguinal approach to fragments of the acetabular surface that were displaced distally. Thereby, reposition of a craniolateral fragment was achieved without the need to extend the surgical approach or to perform a second incision.


Subject(s)
Acetabulum/injuries , Fractures, Bone/surgery , Hip Dislocation/surgery , Ilium/surgery , Joint Loose Bodies/surgery , Multiple Trauma/surgery , Osteotomy/methods , Acetabulum/diagnostic imaging , Acetabulum/surgery , Adult , Fracture Fixation, Internal , Fractures, Bone/diagnostic imaging , Hip Dislocation/diagnostic imaging , Humans , Inguinal Canal/diagnostic imaging , Inguinal Canal/surgery , Joint Loose Bodies/diagnostic imaging , Male , Multiple Trauma/diagnostic imaging , Postoperative Complications/diagnostic imaging , Tomography, X-Ray Computed
10.
Chirurg ; 74(4): 361-9, 2003 Apr.
Article in German | MEDLINE | ID: mdl-12719878

ABSTRACT

Improved survival rates of patients with multiple injuries have increased general interest in the quality of rehabilitation status after polytrauma. Due to the complex nature of multiple injuries, a special score is needed to evaluate the outcome after polytrauma. The aim of this study was to validate the Hannover Score for Polytrauma Outcome (HASPOC). One hundred seventy patients who had sustained multiple injuries were re-examined using the HASPOC 2 years after trauma. Results were correlated with the 12-Item Short Form Health Survey (SF-12), a validated and established scoring system. The HASPOC was also correlated with clinical parameters predictive of poor outcome. Two control groups consisting of either patients after single injuries or healthy controls were also evaluated using the HASPOC. In the group of patients after multiple injuries, the HASPOC correlated with the SF-12 in injury severity and polytrauma scores, intubation period, hospital stay, and occurrence of injuries below the knee. Differences between healthy controls,patients after single injuries, and patients after multiple injuries were statistically significant when evaluated with the HASPOC. This statistical significance was not achieved using the SF-12. The HASPOC is a valid scoring system and useful for evaluating the rehabilitation status after polytrauma.


Subject(s)
Multiple Trauma/rehabilitation , Outcome Assessment, Health Care/statistics & numerical data , Adolescent , Adult , Aged , Female , Follow-Up Studies , Germany , Health Surveys , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Multiple Trauma/mortality , Reference Values , Registries , Reproducibility of Results , Survival Rate , Trauma Severity Indices , Treatment Outcome
11.
J Hosp Mark ; 13(2): 43-61, 1999.
Article in English | MEDLINE | ID: mdl-10915390

ABSTRACT

Microcomparison, or single-component analysis, of health care systems offers a potentially better basis for reform than traditional macrocomparison analysis of aggregate elements. Using macroanalysis, available evidence shows that Germany provides cheaper but more effective hospital care than the United States. To find the causes for this outcome, we developed a microanalytic model of hospital administrators' perceptions, financial ratios, medical outcomes, and pharmaceutical costs. However, only data on pharmaceutical costs were available, and these were similar in both countries. Our significant outcome was development of a microcomparative model that gives world medical care providers new criteria for analyzing and improving cost to care ratios.


Subject(s)
Health Care Reform , Health Policy , Hospitals , Delivery of Health Care/economics , Delivery of Health Care/organization & administration , Delivery of Health Care/standards , Germany , Models, Organizational , Quality of Health Care , United States
12.
Hum Genet ; 82(2): 142-6, 1989 May.
Article in English | MEDLINE | ID: mdl-2566575

ABSTRACT

Human pepsinogen A (PGA) displays highly polymorphic isozymogen patterns after polyacrylamide gel electrophoresis and activity staining. The patterns differ with respect to the presence and the relative intensity of the individual fractions. Family studies strongly suggest that these isozymogen patterns are encoded by allelic haplotypes, encompassing different numbers and types of PGA genes. In this paper, we confirm the essential features of this multigene model. We establish the relationship between the haplotypes and the corresponding isozymogen patterns by determination of the PGA polymorphism at both the DNA and the protein level in 117 Dutch individuals, 60 of whom were unrelated. The combination of HindIII and EcoRI restriction fragment length polymorphisms (RFLPs) has enabled us to define different haplotypes, which are shown to segregate within families. Most genes are characterized by their specific EcoRI fragments. The HindIII RFLP is in strong linkage disequilibrium with PGA genes showing strong expression of the relevant isozymogen. Although a general picture of the relationship between genotypes and phenotypes is emerging, there are exceptions, suggesting that rare haplotypes evolve by unique crossover events.


Subject(s)
DNA/analysis , Pepsinogens/genetics , DNA Restriction Enzymes , Electrophoresis, Polyacrylamide Gel , Genotype , Haplotypes , Humans , Multigene Family , Pedigree , Phenotype , Polymorphism, Restriction Fragment Length
13.
Genomics ; 4(3): 232-9, 1989 Apr.
Article in English | MEDLINE | ID: mdl-2714789

ABSTRACT

To unravel the genetic basis for the pepsinogen A (PGA) protein polymorphism, we have isolated and characterized a number of PGA genes, distinguishable by polymorphic EcoRI fragments of 12.0, 15.0, and 16.6 kb. Using a HindIII or AvaII polymorphism, we can discriminate between different 15.0 (15.0 and 15.0*) and 12.0 (12.0s and 12.0l) genes, respectively. The coding sequences of a 15.0 and a 16.6 gene were determined, together with considerable stretches of the 5'- and 3'-flanking regions and introns. The genes were demonstrated to encode Pg5 and Pg4, respectively. Because substitutions in codons 43 and 207 appeared to be critical in the determination of the encoded proteins, we sequenced only these regions in the two 12.0 genes and the 15.0* gene. On the basis of these partial sequences, we assume that these genes encode Pg3. In the evolutionary model of the PGA gene cluster presented here, the 12.0 genes arose by an unequal, but homologous crossover. The results of sequence analysis of the second intron of the 12.0s, 12.0l, 15.0, and 16.6 genes suggest that the two 12.0 genes have arisen from two different crossover events.


Subject(s)
Multigene Family , Pepsinogens/genetics , Amino Acid Sequence , Base Sequence , Biological Evolution , Genes , Humans , Molecular Sequence Data , Sequence Homology, Nucleic Acid
14.
Gene ; 65(2): 179-85, 1988 May 30.
Article in English | MEDLINE | ID: mdl-2900796

ABSTRACT

The complete nucleotide sequence of Rhesus monkey (Macaca mulatta) pepsinogen A (PGA) cDNA was determined from two partially overlapping cDNA clones, covering the whole coding sequence and part of the flanking sequences. The nucleotide and deduced amino acid sequences were compared to known PGA sequences from other species. The degree of similarity with human PGA appeared to be 96% at the nucleotide sequence level and 94% at the amino acid sequence level. In the coding region the divergence was highest in the activation peptide. The amino acid sequence similarity between Japanese monkey (Macaca fuscata) PGA and Rhesus monkey PGA was shown to be 99%. Using the cDNA as probe in Southern hybridization of EcoRI-digested human and Rhesus monkey genomic DNAs, PGA patterns with inter-individual differences were observed. The hybridization patterns are compatible with the existence of a PGA multigene family in both species.


Subject(s)
Cloning, Molecular , DNA/genetics , Macaca mulatta/genetics , Macaca/genetics , Pepsinogens/genetics , Amino Acid Sequence , Animals , Molecular Sequence Data , Plasmids , Polymorphism, Restriction Fragment Length , Protein Biosynthesis , Sequence Homology, Nucleic Acid
15.
Hum Genet ; 78(1): 79-82, 1988 Jan.
Article in English | MEDLINE | ID: mdl-2892778

ABSTRACT

A human cosmid library was screened with a pepsinogen A (PGA) cDNA probe, yielding 18 clones with (parts of) one, two or three PGA genes. By aligning these cosmids a restriction map of a PGA gene quadruplet was obtained in which the four genes are arranged in a highly ordered fashion in a head-to-tail orientation. Using the length in kilobases of the large polymorphic EcoRI fragment of the PGA genes, this quadruplet can be described as 15.0-12.0-12.0-16.6. An AvaII polymorphism allowed us to identify the two PGA haplotypes of the individual whose DNA had been cloned in the cosmid library to be a gene triplet and a gene quadruplet. By comparing the restriction maps of the central 12.0 genes in these multiplets to those of the flanking 15.0 and 16.6 genes, we postulate that these central genes arose from unequal but homologous crossing over between two 15.0-16.6 gene pairs. This hypothesis provides for the creation of a variety of haplotypes by additional cross overs and mutations. Southern blots of family and population material supports the existance of at least five common PGA haplotypes, including a single-gene haplotype, giving rise to a large number of different EcoRI patterns. The single PGA gene is probably the reciprocal crossing over product. Comparison between the DNA and protein polymorphisms suggests further micro-heterogeneity in the different PGA haplotypes.


Subject(s)
Multigene Family , Pepsinogens/genetics , Biological Evolution , Cloning, Molecular , Cosmids , Crossing Over, Genetic , Humans , Polymorphism, Restriction Fragment Length
16.
Hum Genet ; 77(2): 182-7, 1987 Oct.
Article in English | MEDLINE | ID: mdl-3115885

ABSTRACT

Three human cosmid clones containing pepsinogen A (PGA) encoding sequences were isolated from a genomic bank derived from a single individual. One cosmid contains two PGA genes in tandem in a head-to-tail orientation, while the other two cosmids each contain a single PGA gene. The three cosmids were characterized by restriction mapping and sequence analysis (exons 1 and 2 and flanking regions). As judged from these data, three of the four PGA genes isolated appear to be nearly identical, but one of the tandem genes is clearly different from the other genes. The first exon of all four genes codes for the same amino acid sequence. However, in the second exon of one of the tandem genes we found a nucleotide substitution giving rise to a Glu----Lys substitution of the 43rd amino acid residue of the activation peptide, leading to a charge difference of the corresponding isozymogens. The presence of two distinct PGA genes in the isolated gene pair conclusively proves the multigene structure of the PGA system. These genes might be responsible for at least part of the electrophoretic polymorphism at the protein level.


Subject(s)
Cloning, Molecular , Multigene Family , Mutation , Pepsinogens/genetics , Amino Acid Sequence , Chromosome Mapping , Cosmids , Exons , Glutamine , Humans , Lysine , Molecular Sequence Data
17.
J Gen Virol ; 66 ( Pt 11): 2395-406, 1985 Nov.
Article in English | MEDLINE | ID: mdl-2997373

ABSTRACT

Human cell lines that contain and express the gene encoding the adenovirus type 5 DNA-binding protein (Ad5 DBP) are very useful for the isolation of adenovirus mutants with an altered DBP. In order to obtain these cells, human 143 tk- cells were transfected, using the calcium phosphate technique, with plasmids containing the Ad5 DBP gene and the herpes simplex virus thymidine kinase (HSV tk) gene as a selectable marker. Characterization of several tk+ transformants revealed that these cells did contain the HSV tk gene, but in none of these cells could Ad5 DBP DNA sequences be detected. However, when 143 tk- cells were co-transfected with a plasmid containing the Ad5 DBP gene and another plasmid carrying early region E1, integration of the Ad5 DBP gene in chromosomal DNA could be detected. Integration of Ad5 DNA sequences was also observed when transfection was performed with plasmids containing the Ad5 DBP gene and the long terminal repeat of Moloney murine leukaemia virus. By employing a radioimmunoassay it could be shown that DBP-related proteins were synthesized in two of the cell lines containing the Ad5 DBP gene. Since both cell lines support the growth of the temperature-sensitive viral DBP mutant, H5ts125, at the non-permissive temperature, the DBP-related proteins expressed in these cells must be functional.


Subject(s)
Adenoviruses, Human/genetics , DNA-Binding Proteins/genetics , Genes, Viral , Plasmids , Transfection , Viral Proteins/genetics , Adenoviruses, Human/growth & development , Cell Line , DNA Restriction Enzymes , DNA-Binding Proteins/biosynthesis , Deoxyribonuclease HindIII , Humans , Moloney murine leukemia virus/genetics , Mutation , Recombination, Genetic , Repetitive Sequences, Nucleic Acid , Simplexvirus/enzymology , Simplexvirus/genetics , Thymidine Kinase/biosynthesis , Thymidine Kinase/genetics , Transcription, Genetic , Viral Proteins/biosynthesis
18.
Hum Genet ; 70(4): 337-40, 1985.
Article in English | MEDLINE | ID: mdl-3839486

ABSTRACT

A 0.9kb cDNA fragment, corresponding to a large part of Rhesus monkey pepsinogen A mRNA, was used as probe for the chromosomal localization of the human pepsinogen A gene(s) using human-rodent somatic cell hybrids. Southern blot analysis of 14 human-Chinese hamster and three human-mouse cell hybrids, strongly indicates that the human PGA locus is on chromosome 11. The human-mouse hybrids, containing a translocation involving chromosome 11, allow sublocalization to the region q12-pter.


Subject(s)
Chromosomes, Human, 6-12 and X , Pepsinogens/genetics , Animals , Chromosome Mapping , Cricetinae , Cricetulus , DNA/genetics , Humans , Hybrid Cells/enzymology , Macaca mulatta/genetics , Mice
19.
J Biol Chem ; 258(15): 9059-68, 1983 Aug 10.
Article in English | MEDLINE | ID: mdl-6874677

ABSTRACT

Inhibition of poly(ADP-ribose) synthesis by 3-aminobenzamide in various human and hamster cells influenced the responses to DNA damage from methyl methanesulfonate, but not from ultraviolet light. After exposure to methyl methanesulfonate, 3-aminobenzamide increased the strand break frequency in all cell types studied, but only stimulated repair replication in lymphoid and HeLa cells, suggesting these are independent effects. 3-Aminobenzamide also inhibited the pathway for de novo synthesis of DNA purines, suggesting that some of its effects may be due to disturbance of precursor pathways and irrelevant to the role of poly(ADP-ribose) in repair. Previous claims that 3-aminobenzamide stimulates repair synthesis after exposure to UV light are probably artifacts, because the stimulations are only observed in lymphocytes in the presence of a high concentration of hydroxyurea that itself inhibits repair. The initial inhibition of semiconservative DNA synthesis and the excision of the major alkylation products and pyrimidine dimers were unaffected by 3-aminobenzamide. In general poly(ADP-ribose) synthesis appears to be uniquely involved in regulating the ligation stage of repair of alkylation damage but not ultraviolet damage. By regulating the ligation efficiency, poly(ADP-ribosylation) modulates the dynamic balance between incision and ligation, so as to minimize the frequency of DNA breaks. The ligation stage of repair of UV damage appears different and is not regulated by poly(ADP-ribosylation).


Subject(s)
DNA Repair , Nucleoside Diphosphate Sugars/metabolism , Poly Adenosine Diphosphate Ribose/metabolism , Ultraviolet Rays , Animals , Benzamides/pharmacology , Cell Line , Cricetinae , Cricetulus , DNA/radiation effects , Female , Fibroblasts/metabolism , HeLa Cells/metabolism , Humans , Methyl Methanesulfonate/pharmacology , Ovary/metabolism , Poly Adenosine Diphosphate Ribose/biosynthesis
20.
J Invest Dermatol ; 77(1): 96-101, 1981 Jul.
Article in English | MEDLINE | ID: mdl-7252263

ABSTRACT

Xeroderma pigmentosum (XP) occurs with high frequency in Egypt and a continuation of our field studies has identified representatives of the 3 major complementation groups A, C, and variant. Group A patients, with one exception, showed very early onset of sun sensitivity and development of skin cancers, and microcephaly and mental retardation. The exceptional group A patient was 35 yr old, with normal stature and intelligence who had 2 normal children. DNA repair was as low in his cells as in other group A cases. Group C patients showed a slightly slower onset of sun sensitivity and had no central nervous system disorders. The variants showed later onset of sun sensitivity and no skin cancers evident at the time of observation (about 20 yr of age). No sun sensitivity was present in the 25 heterozygotes we observed, nor reportedly in the additional 60 not yet observed. This indicates that only homozygosity for XP genes increases risk of skin cancer. Cell cultures from both normal persons and these XP patients reached in vitro "senescence" at similar passage levels. Groups A and C appear to have lost different major gene products that are involved in the excision of UV damage from DNA, but the residual repair in XP-C cells facilitates more recovery of DNA synthesis than in other groups. This may contribute to the higher in vitro survival in culture and milder clinical symptoms in group C as compared to group A. XP variants appear to have lost a gene product that permits normal cells to replicate, uninterrupted by DNA damage, and consequently synthesize DNA in smaller pieces than normal.


Subject(s)
Xeroderma Pigmentosum/pathology , Adult , Cells, Cultured , Complement System Proteins , DNA Repair , DNA Replication , Egypt , Female , Humans , Male , Xeroderma Pigmentosum/epidemiology , Xeroderma Pigmentosum/immunology
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