Extradural spinal hydatid cyst causing hindlimb ataxia in a horse.

INTRODUCTION: This case report describes a 13-year-old cob-cross gelding presented for evaluation of recent onset hindlimb ataxia. The gelding had undergone general anaesthesia and tenoscopy of the right hindlimb digital flexor tendon sheath at a nearby clinic three months earlier and had appeared normal at routine post-operative assessments until the sudden onset of neurological deficits. Spinal trauma was suspected initially but radiography and scintigraphy were unremarkable. Due to the severity and progressive nature of the clinical signs the -gelding was subjected to euthanasia. Post mortem examinations (computed tomography, dissection and histopathology) revealed spinal cord compression caused by a single extradural hydatid cyst (Echinococcus equinus), confirmed with PCR, at the level of the 15th thoracic vertebra. This is the first report of a spinal hydatid cyst causing hindlimb ataxia and should therefore be considered a potential differential diagnosis for ataxia in the equine patient.

INTRODUCTION: Ce rapport décrit le cas d'un hongre croisé cob de 13 ans présenté pour l'évaluation d'une ataxie des membres postérieurs d'apparition récente. Le hongre avait subi une anesthésie générale et une ténoscopie de la gaine du tendon du fléchisseur digital du membre postérieur droit dans une clinique voisine trois mois auparavant et avait semblé normal lors des évaluations postopératoires de routine jusqu'à l'apparition soudaine de déficits neurologiques. Un traumatisme rachidien était suspecté au départ, mais la radiographie et la scintigraphie étaient sans particularité. En raison de la gravité et de la nature progressive des signes cliniques, le hongre a été euthanasié. Les examens post mortem (tomodensitométrie, dissection et histopathologie) ont révélé une compression de la moelle épinière provoquée par un unique kyste hydatique extradural (Echinococcus equinus), confirmé par PCR, au niveau de la 15e vertèbre thoracique. Il s'agit du premier cas rapporté d'un kyste hydatique au niveau de la colonne vertébrale causant une ataxie des membres postérieurs et doit donc être considéré comme un diagnostic différentiel potentiel de l'ataxie chez le patient équin.

The transcriptome of human oocytes is related to age and ovarian reserve.

STUDY QUESTION: How does the human oocyte transcriptome change with age and ovarian reserve? SUMMARY ANSWER: Specific sets of human oocyte messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) are affected independently by age and ovarian reserve. WHAT IS KNOWN ALREADY: Although it is well established that the ovarian reserve diminishes with increasing age, and that a woman's age is correlated with lower oocyte quality, the interplay of a diminished reserve and age on oocyte developmental competence is not clear. After maturation, oocytes are mostly transcriptionally quiescent, and developmental competence prior to embryonic genome activationrelies on maternal RNA and proteins. STUDY DESIGN, SIZE, DURATION: A total of 36 vitrified/warmed MII oocytes from 30 women undergoing oocyte donation were included in this study, processed and analyzed individually. PARTICIPANTS/MATERIALS, SETTING, METHODS: Total RNA from each oocyte was independently isolated, amplified, labeled, and hybridized on HTA 2.0 arrays (Affymetrix). Data were analyzed using TAC software, in four groups, each including nine oocytes, according to the woman's age and antral follicular count (AFC) (mean ± SD): Young with High AFC (YH; age 21 ± 1 years and 24 ± 3 follicles); Old with High AFC (OH; age 32 ± 2 years and 29 ± 7 follicles); Young with Low AFC (YL; age 24 ± 2 years and 8 ± 2 follicles); Old with Low AFC (OL; age 34 ± 1 years and 7 ± 1 follicles). qPCR was performed to validate arrays. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a set of 30 differentially expressed mRNAs when comparing oocytes from women with different ages and AFC. In addition, 168 non-coding RNAs (ncRNAs) were differentially expressed in relation to age and/or AFC. Few mRNAs have been identified as differentially expressed transcripts, and among ncRNAs, a set of Piwi-interacting RNAs clusters (piRNAs-c) and precursor microRNAs (pre-miRNAs) were identified as increased in high AFC and old groups, respectively. Our results indicate that age and ovarian reserve are associated with specific ncRNA profiles, suggesting that oocyte quality might be mediated by ncRNA pathways. LARGE SCALE DATA: Data can be found via GEO accession number GSE87201. LIMITATIONS, REASONS FOR CAUTION: The oldest woman included in the study was 35 years old, thus our results cannot readily be extrapolated to women older than 35 or infertile women. WIDER IMPLICATIONS OF THE FINDINGS: We show, for the first time, that several non-coding RNAs, usually regulating DNA transcription, are differentially expressed in relation to age and/or ovarian reserve. Interestingly, the mRNA transcriptome of in vivo matured oocytes remains remarkably stable across ages and ovarian reserve, suggesting the possibility that changes in the non-coding transcriptome might regulate some post-transcriptional/translational mechanisms which might, in turn, affect oocyte developmental competence. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by intramural funding of Clinica EUGIN and by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia. J.H. and A.S. are employees of Affymetrix, otherwise there are no competing interests.

Suitability of Fourier transform infrared microscopy for the diagnosis of cystic echinococcosis in human tissue sections.

Cystic echinococcosis (CE) is a global health concern caused by cestodes, posing diagnostic challenges due to nonspecific symptoms and inconclusive radiographic results. Diagnosis relies on histopathological evaluation of affected tissue, demanding comprehensive tools. In this retrospective case study, Fourier transform infrared microscopy was explored for detecting and identifying CE through biochemical changes in human tissue sections. Tissue samples from 11 confirmed CE patients were analyzed. Archived FFPE blocks were cut and stained, and then CE-positive unstained sections were examined using Fourier transform infrared microscopy post-deparaffinization. Results revealed the method's ability to distinguish echinococcus elements from human tissue, irrespective of organ type. This research showcases the potential of mid-infrared microscopy as a valuable diagnostic tool for CE, offering promise in enhancing diagnostic precision in the face of the disease's complexities.

Parasitoses of the human central nervous system.

Cerebral involvement in parasitoses is an important clinical manifestation of most of the human parasitoses. Parasites that have been described to affect the central nervous system (CNS), either as the dominant or as a collateral feature, include cestodes (Taenia solium (neurocysticerciasis), Echinococcus granulosus (cerebral cystic echinococcosis), E. multilocularis (cerebral alveolar echinococcosis), Spirometra mansoni (neurosparganosis)), nematodes (Toxocara canis and T. cati (neurotoxocariasis), Trichinella spiralis (neurotrichinelliasis), Angiostrongylus cantonensis and A. costaricensis (neuroangiostrongyliasis), Gnathostoma spinigerum (gnathostomiasis)), trematodes (Schistosoma mansoni (cerebral bilharziosis), Paragonimus westermani (neuroparagonimiasis)), or protozoa (Toxoplasma gondii (neurotoxoplasmosis), Acanthamoeba spp. or Balamuthia mandrillaris (granulomatous amoebic encephalitis), Naegleria (primary amoebic meningo-encephalitis), Entamoeba histolytica (brain abscess), Plasmodium falciparum (cerebral malaria), Trypanosoma brucei gambiense/rhodesiense (sleeping sickness) or Trypanosoma cruzi (cerebral Chagas disease)). Adults or larvae of helminths or protozoa enter the CNS and cause meningitis, encephalitis, ventriculitis, myelitis, ischaemic stroke, bleeding, venous thrombosis or cerebral abscess, clinically manifesting as headache, epilepsy, weakness, cognitive decline, impaired consciousness, confusion, coma or focal neurological deficits. Diagnosis of cerebral parasitoses is dependent on the causative agent. Available diagnostic tools include clinical presentation, blood tests (eosinophilia, plasmodia in blood smear, antibodies against the parasite), cerebrospinal fluid (CSF) investigations, imaging findings and occasionally cerebral biopsy. Treatment relies on drugs and sometimes surgery. Outcome of cerebral parasitoses is highly variable, depending on the effect of drugs, whether they are self-limiting (e.g. Angiostrongylus costaricensis) or whether they remain undetected or asymptomatic, like 25% of neurocysticerciasis cases.

Toxocariasis and the clinical spectrum.

Toxocara canis and T. cati are among the most widely distributed helminthic species in the world with a high zoonotic impact. Millions of people are infecteda and hundreds of thousands are suffering from toxocarosis, a disease encompassing four different entities: larva migrans visceralis (VLM) syndrome, ocular larva migrans (OLM) syndrome, covert toxocarosis (covT), common toxocarosis (comT) and neurotoxocarosis (NT). Toxocara infections in humans may remain clinically inapparent but may also induce severe diseases. This contribution gives a synoptic overview of the most important historical, clinical, diagnostic and therapeutical aspects of toxocarosis in humans.

[The first case of anisakiasis acquired in Austria]. / Anisakiasis - der erste in Osterreich akquirierte Fall einer seltenen Helminthozoonose.

Anisakiasis is caused by a fish parasite of the Nematode family. This kind of rare helminthozoonosis can mainly be found in countries where consumption of raw fish is traditionally high like Japan, the Netherlands, Pacific Islands, South Europe, Scandinavia, USA, and Canada. Man is the wrong hoste. Clinical manifestation depends on the localisation of penetration in the GI tract. In Japan, predominantly the stomach is affected in 97 % of cases, probably due to hypo- and achlorhydria; whereas mainly intestinal anisakiasis occurs in Europa. We report on a 67-year-old male patient with a gastric infestation of anisakiasis. The patient was on proton pump inhibitor which migh have caused the localisation of the infestation. The anisakis was an accidental endoscopic finding in a patient for control of an H. p.-positive gastric ulcer. Otherwise the patient was free of pain. The helminth (larva III) was endoscopically extracted. Thereafter, the patient remained in good health. Anisakis serology as well as repeated differential blood counts were without finding. The uneventful medical history and the normal blood findings indicate that our patient had a very early stage of infestation of anisakiasis. The patient reported no stay outside of Austria within the last years. However, he consumed on a regular basis "rolled pickled herring" produced by a well-known Viennese company for canned fish. This is the first documented case of this rare helminthozoonosis acquired in Austria.

Expression divergence and copy number variation in the human genome.

DNA copy number variation (CNV) was recently discovered as a significant part of human genetic variation. This variation affects genes as well as intergenic regions. Herein, current insight into the effects of CNV on gene expression is summarized. The consequences of intergenic CNVs are poorly understood. For CNV affecting genes, a dosage compensation mechanism seems to be applied on a subset of genes only, while others show augmented expression caused by increasing copy number. For the latter case, extensive literature reports a positive correlation between gene copy number and gene expression. Recent advances in techniques for genome-wide measurements of CNV and gene expression are described. These advances will soon allow the generation of comprehensive maps of these two phenomena, which will contribute to our understanding of the mechanisms underlying how CNV affects gene expression.

Evaluation of follow-up of therapy with fenbendazole incorporated into stabilized liposomes and immunomodulator glucan in mice infected with Toxocara canis larvae.

Anthelmintic activity of benzimidazole carbamate anthelmintics is low against dormant Toxocara canis larvae during late infections in paratenic hosts. The present study was conducted to examine the efficacy of pure fenbendazole, or drug incorporated into sterically stabilized liposomes (SL-FBZ) administered to T. canis-infected mice alone and after its co-administration with the immunomodulator (1-->3)-beta-D-glucan against larvae localized in muscles and brains. Therapy with either drug forms (in total 250 mg/kg in 10 doses) commenced on day 28 post-infection (p.i.) and the efficacy of treatment, examined on day 30 after the last dose of drug, was the highest in groups of mice treated with SL-FBZ in combination with glucan (89.5+/-5.8% in the muscles, 66.1+/-8.1% in brains). During 56 days of follow-up after termination of therapy, serum levels of anti-TES IgG antibodies, circulating IgG-TES immune complexes (CIC) as well as IgG antibodies to the most immunogenic part of recombinant myosin antigen of T. canis larvae were investigated. In contrast to anti-TES IgG antibodies, levels of CIC and anti-myosin antibodies were in the linear correlation with the efficacy of treatments beginning from day 38 post-therapy. We also showed that the serum levels of CIC as well as anti-myosin IgG antibodies seem to be the suitable serological markers for the monitoring of progress in larval destruction and TES resorption from the tissues.

Three-dimensional structure of the Fab fragment of a neutralizing antibody to human rhinovirus serotype 2.

The crystal structure of the antigen-binding fragment of a monoclonal antibody (8F5) that neutralizes human rhinovirus serotype 2 has been determined by X-ray diffraction studies. Antibody 8F5, obtained by immunization with native HRV2 virions, cross-reacts with peptides of the viral capsid protein VP2, which contribute to the neutralizing immunogenic site B in this serotype. The structure was solved by the molecular replacement method and has been refined to an R-factor of 18.9% at 2.8 A resolution. The elbow angle, relating the variable and constant modules of the molecule is 127 degrees, representing the smallest elbow angle observed so far in an Fab fragment. Furthermore, the charged residues of the epitope can be well accommodated in the antigen-binding site. This is the first crystal structure reported for an antibody directed against an icosahedral virus.

Purification and characterisation of the restriction endonuclease ItaI from Ilyobacter tartaricus recognizing 5'-GC decreases NGC-3'.

ItaI, an isoschizomer of the subclass IIW [Kessler and Manta, Gene 92 (1990) 1-248] restriction endonuclease (ENase), Fnu4HI [Leung et al., Nucleic Acids Res. 6 (1979) 17-25], has been isolated from Ilyobacter tartaricus. The ENase has the five-base palindromic recognition sequence, 5'GC decreases NGC-3'. It cleaves behind the second nucleotide and produces a one-nt 5' overhang.

Human low density lipoprotein as a target of hypochlorite generated by myeloperoxidase.

The aim of this study was to further clarify which part of human low density lipoprotein (LDL) is attacked by the MPO/H2O2/Cl- -system and which reactive oxygen species is responsible for the attack. Therefore the influence of this system on the modification of the lipid and protein moiety of LDL was studied in vitro. Using the monochlorodimedone assay it was found that HOCl is produced in micromolar quantities in the absence of LDL and is rapidly consumed by LDL in a concentration dependent manner. The consumption of HOCl was reflected in the formation of HOCl-specific epitopes on apo B-100 as determined by an antibody raised against HOCl-modified LDL. The absorbency at 234 nm was applied to measure continuously the extent of modification of LDL. The general kinetic pattern of the absorbency measurement consisted of a lag phase where no LDL modification was observed, followed by a rapid increase of absorbency and a plateau phase. Finally the absorbency decreased due to LDL precipitation. Time dependent absorption spectra indicated that this kinetic pattern is mainly caused by light scattering due to particle aggregation rather than by a specific absorption at 234 nm due to conjugated diene formation. In agreement with this finding a low rate of thiobarbituric acid reactive substances (TBArS) formation was observed after a lag phase. The aggregation of LDL occurs most likely by modification of apo B-100, which was determined fluorimetrically in terms of LDL-tryptophan destruction in presence of the MPO/H2O2/Cl(-)-system. The kinetic course of tryptophan fluorescence generally consisted of a rapid decrease leveling off into a low plateau phase. Gas chromatographic determinations of linoleic acid in LDL in presence of the MPO system showed that this polyunsaturated fatty acid (PUFA) is easily attacked by HOCl. Consistent with this finding NMR spectra of HOCl modified LDL indicated a complete disappearance of bis-allylic methylene groups. Since lipid peroxidation products only partially account for this loss of PUFAs, other reactions of HOCl with unsaturated lipids--probably chlorohydrin formation--must be involved. Summarizing, although the rate of lipid peroxidation is low, both the lipid and the protein moiety of LDL are readily modified by the MPO system. It appears that the immediate consequence of apo B-100 modification is its aggregation. It is concluded that MPO, which has been detected in atherosclerotic lesions, is able to contribute to the modification of LDL into a form recognizable for uncontrolled uptake by macrophages.

Antioncogene P53 and mitogenic cytokine interleukin-8 aberrantly expressed in psoriatic skin are inversely regulated by the antipsoriatic drug tacrolimus (FK506).

Uncontrolled proliferation of epidermal cells is the most prominent characteristic of psoriasis. This widespread skin disease can be effectively treated with the microbial substance FK506, which acts by modulating gene expression. We, therefore, asked if the drug changes the expression of genes involved in growth regulation (the mitogenic cytokine interleukin-8 (IL-8) and p53, a negative cell cycle regulator) and signal transduction (protooncogenes c-ras, c-raf, and HER-2). Gene expression was monitored by semiquantitative mRNA-PCR and for p53 by immunocytochemistry in cultured primary keratinocytes (KC). In addition, p53 expression was analysed in skin biopsies of psoriatic patients. After 1-3 hr, IL-8 mRNA levels were dose-dependently decreased in tacrolimus (FK506)-treated cells. Protooncogene expression was not significantly altered. Interestingly, p53 transcription was clearly induced by FK506 treatment. This tendency could be verified on the protein level by immunocytochemistry. In contrast, p53 expression was decreased in lesional psoriatic as compared to normal skin, providing evidence that not only posttranslational modification of the p53 protein, but also transcriptional modulation of the p53 gene, are involved in pathological processes and pharmacological drug action in skin. Together with earlier results showing downmodulation for IL-8 receptor type A expression in cultured KC treated with FK506, these results suggest that both the mitogenic IL-8/IL-8R system and the cell cycle inhibitor p53 represent potential targets for the antipsoriatic action of the drug, whereas protooncogenes acting downstream in mitogenic signal transduction cascades are unaffected. The differential modulation of an entire set of genes provides evidence for the specificity of the drug effects and rules out nonspecific toxic effects on KC.

Allogeneic bone marrow transplantation-mediated transfer of specific immunity against Toxocara canis associated with excessive IgE.

A girl with myelodysplastic syndrome (RAEB-T) received HLA-identical bone marrow from her younger brother after myeloablative treatment with busulfan and cyclophosphamide. After bone marrow transplantation, fever, exanthema, pruritus, and a pulmonary infiltrate were treated symptomatically. Bacterial cultures remained negative. Leukocyte engraftment began on day 10, and all blood cell populations proved to be of donor origin on FISH analysis. Increasing IgE levels (21 000 U/ml) on day 14 after BMT, positive RAST, specific IgG-antibodies, and missing Toxocara (T.) canis antigens in the recipient indicated donor-derived seroconversion. Before BMT, the recipient had been negative for T. canis in routine parasitological screening, and the donor proved to be positive for T. canis antibody by ELISA. This report suggests that the transfer of IgE immunity in the absence of detectable antigens may be responsible for IgE-mediated symptoms consistent with toxocara infection and confirms the need for parasite screening in donor medical examinations.

Valve repair in mitral regurgitation complicated by severe annulus calcification.

BACKGROUND: Valvuloplasty has significant advantages over valve replacement for mitral regurgitation, but the presence of severe calcification of the mitral valve apparatus has been thought to preclude successful valve reconstruction in general. The purpose of this report is to assess the results of valvuloplasty in patients with severe mitral regurgitation having extensive calcification extending from the mitral annulus to underlying myocardium and parts of the papillary muscles. METHODS: Thirty-seven adult patients with severe mitral regurgitation and calcification were operated on between April 1990 and January 1998. Twenty-six patients had degenerative disease, 4 had acute bacterial endocarditis, 6 had postrheumatic fever, and 1 patient had Marfan's disease. The valve repair comprised of en bloc decalcification with extensive leaflet debridement and reconstruction of the annulus. Autologous pericardium was used in patch-extended endocardial annuloplasty or leaflet repair. Valve competence was retained after correction of regurgitation by sliding atrioplasty, rotation paracommissural sliding plasty, cusp remodeling, or chordal repair. All patients required a prosthetic annuloplasty. RESULTS: Follow-up echocardiography at 47 months (range, 3 to 92 months) showed no or only trivial mitral regurgitation in 33 patients; 3 had grade I-II mitral regurgitation and 1 required valve replacement after 3 months. Freedom of reoperation at 1 and 5 years was 94.6%. At last examination, 33 patients were in New York Heart Association functional class I and 3 in class I-II; there has been no mortality and no thromboembolic events. CONCLUSIONS: Valvuloplasty can be safely and successfully carried out in patients suffering from regurgitation associated with severe calcification of the mitral apparatus. With encouraging beneficial midterm results, we suggest patients with calcified valves should not be excluded from mitral repair.

Kinetics of the disordered chain-to-beta transformation of poly(L-tyrosine) in aqueous solution.

The kinetics of the transformation of poly(L-tyrosine) from the disordered chain to the intramolecular beta structure in aqueous solution has been studied. The reaction is induced by an isothermal pH jump and is followed by conventional circular dichroism methods. Upon application of curve-fitting procedures, it is found that the kinetics are poorly represented by a single first-order process, but a two-step sequential first-order equation is adequate. Sharp pH-dependent maxima in the phenomenological rate constants and in the fractional amplitude of the rapid step were found. It is proposed to attribute these phenomena to a transition in initial states which is shown to occur over the same pH range within the domain of the disordered-to-beta transition. No sigmoid transient curves were observed, indicating that no slow nucleation events are discernible in this system. These observations contrast strikingly with the mechanism elaborated for beta formation in (Lys)n [R. Hartman et al., J. Mol. Biol. 90 (1974) 415].

Spatial structures of the bradykinin potentiating peptide F from Agkistrodon piscivorus piscivoris venom.

Bradykinin potentiating peptides usually show two different activities, potentiation of bradykinin and inhibition of angiotensin converting enzyme (ACE). Exceptions of this rule have been found suggesting that both effects occur independently. This study of peptide F by means of NMR spectroscopy shows clearly two different main conformations of the molecule. These different conformations may be the reason for the different activities.

Pulmonary echinococcosis (hydatidosis) in children: results of surgical treatment.

From 1986-1996, 33 children with 49 pulmonary hydatid cysts underwent surgical treatment in Vienna and Istanbul. Cysts were unilateral in 28 and bilateral in 5 cases; unruptured cysts (URC) were diagnosed in 19 patients, and 14 children presented with ruptured cysts (RC). Ten patients had cysts in other organs (liver, spleen, central nervous system) in addition to pulmonary cysts. Diagnosis was primarily based on chest X-ray and computed tomography scan. In Austrian children, a new combination of serological tests was used successfully (71% positive). The standard surgical procedure was cystotomy followed by capitonnage. The main postoperative complications were fever and wound infection. There were two recurrences after a mean follow-up of 4.8 years, and one patient died because of multiple organ involvement. We conclude that the therapy of choice in pediatric pulmonary hydatidosis is complete surgical elimination of the cyst by cystotomy and capitonnage, whereas more extended resections should be avoided. Ideally, benzimidazole treatment should be combined with surgery. New serological tests can improve diagnostic accuracy.

Sleep deprivation does not induce sister chromatid exchange in humans.

In a preliminary study Bamezai and Kumar (1992) reported that a 24-h period of sleep deprivation may raise sister chromatid exchange (SCE) frequencies up to 193% in peripheral blood lymphocytes. This was reinvestigated to clarify the role of sleep duration as a confounder for SCE, which is a well-established parameter for biomonitoring in occupational medicine. In our study, the SCE baseline and the influence of a 24-h period of sleep deprivation (test period) on SCE were investigated for 20 non-smoking volunteers (10 females and 10 males; 20-29 years of age). There was no significant difference (Pall = 0.094) between the deviations of the two SCE rates of the control period (mean: -0.21 +/- 0.90 SCE) and the differences between SCE rates before and after sleep deprivation (mean: 0.42 +/- 0.94 SCE) of each proband. No significant difference was detected between females and males, and SCE did not correlate with age or sleep duration. Therefore we conclude that the influence of sleep deficit on SCE is in the range of a normal day-to-day variance, and has not to be taken into account when SCE is used for a genotoxic monitoring at the workplaces.

Characterisation of genotoxic properties of 2',2'-difluorodeoxycytidine.

The genotoxic properties of 2',2'-difluorodeoxycytidine (dFdC) were characterised using diploid, mortal low-passage fibroblasts (LPF cells) and the spontaneously transformed fibroblast cell line V79. In both cell types, incorporation of dFdC into the DNA led to an increase of DNA single-strand breaks evaluated by an in situ nick translation assay and to an accumulation of cells in the S-phase of the cell cycle. At concentrations below those leading to cell cycle arrest, dFdC neither induced sister chromatid exchange (SCE) nor structural chromosome aberrations in LPF cells, whereas V79 cells accumulated SCEs as well as chromosome breaks over a broad dose range. In LPF cells treated with dFdC, chromosomal alterations were detected by the micronucleus assay within a narrow concentration range, whereas in V79 cells, a dose-dependent increase in the appearance of micronuclei was seen up to cytotoxic concentrations. In addition, V79 cells went into apoptosis, as evaluated by nuclear fragmentation and condensation, whereas this phenomenon was not detectable in LPF cells.

Variations of p53 in cultured fibroblasts of patients with lung cancer who have a presumed genetic predisposition.

The authors studied cultured skin fibroblasts of 64 patients with lung cancer for constitutive mutations of the p53 tumor suppressor gene by using polymerase chain reaction and single-strand conformation polymorphism covering the entire coding region. The patients were considered to be genetically predisposed because lung cancer had developed in 25 of them before age 46 and because 42 of them had at least one first-degree relative with lung cancer. One mutation was detected at position 235 coding for serine instead of asparagine in the conserved DNA binding domain. The Pro/Pro genotype at codon 72 of p53, considered to harbor an increased risk for lung cancer, could not be detected with increased frequency in this study's patients. From these data, the authors conclude that constitutive variations of the p53 gene do not represent a major genetic determinant for lung cancer.