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Allotransplantation of K248 feline mammary carcinoma cell line in cats. A model for monoclonal antibody guided detection and therapy of human breast cancer.

In response to the need for appropriate models for monoclonal antibody guided detection and therapy of human breast cancer, we developed an allogeneic host-tumor model by injecting K248C and K248P cells into cats. A comparison between the K248C- and K248P-induced tumors with respect to biological behavior and histological appearance was made throughout the study. Allotransplantation of tumor cells was performed both in newborn cats and fetal cats between days 42 and 51 of gestation, but only tumor cells injected by the latter approach resulted in tumor growth in all animals injected. Both tumor cell lines gave rise to progressively growing tumors at the site of injection, metastatic spread of tumor cells to various organs, and death from progression 2-4 months after birth. The predominant histological appearance of the K248C and K248P allografts resembled the cribriform and tubulo-papillary growth patterns, respectively, of the original tumor from which the two cell lines were derived. Autopsy of 1-day kittens showed that metastasis started already in the fetus in the short period between injection of tumor cells and birth. Three predominant patterns of metastases were identified: the pulmonary/pleural type, the abdominal type, and the soft tissue type. A lower incidence of metastases was found in bones and brain. The K248C allografts formed significantly more metastases of the abdominal type than K248P tumors (p less than 0.05). No difference in survival was observed between animals with K248C or K248P allografts. The difference in take rate and latency period between K248C and K248P in athymic mice does not seem to be present in the feline host. The similarity of the present model to spontaneous feline and human mammary carcinoma is discussed.

Animals↗

Effects of hyperthermia on cell survival and patterns of protein synthesis in endothelial cells from different origins.

Thermotolerance, transient resistance to heat induced by heat itself, is generally thought to be linked to the accumulation of heat-shock proteins in eukaryotic cells. The induction of thermotolerance and the synthesis of heat-shock proteins in primary and passage cultures of bovine aortic endothelium, passage cultures of bovine brain capillaries, and passage cultures of rat epididymal capillaries were examined. Primary and passage cultures of bovine aortic endothelial cells readily acquired thermotolerance; however, passage cultures of rat epididymal capillary cells and bovine brain capillary cells were very heat sensitive. In all endothelial cell types examined except rat epididymal capillary cells, the levels of HSP71, the most inducible of the HSP70 family, correlated well with thermotolerance. With prolonged passage, rat epididymal capillary cells and bovine brain capillary cells lost their ability to acquire heat resistance. Endothelial cells from different origins (aortic endothelium versus capillary endothelium) but from the same species and about the same passage number had a notably different response in terms of thermotolerance and synthesis of proteins after exposure to hyperthermia. The results of this study suggest that, while the expression of HSP71 may be a good indicator of heat resistance, the reverse is not necessarily true. Furthermore, the data show that endothelial cells from different origins are dissimilar in their response to hyperthermia.

Animals↗

Middle digestive cancers in Texas Hispanics: a New World syndrome?

To test the hypothesis that middle digestive cancers in Texas Hispanics follow the patterns predicted by the New World Syndrome (1984), cancer incidence rates and relative risks for middle digestive cancers were estimated for 1944-1992. The relative risk for all middle digestive cancers is significantly elevated in Texas Hispanics compared with Anglos, and this risk has increased over time. Elevated risks of these cancers in Texas Hispanics have been explained as resulting from the evolutionary history of Native Americans (American Indians), their genetic relation to Texas Hispanics, and a changing diet and lifestyle. Recent Texas cancer incidence data add further support to the hypothesis. Other current disease prevalence data in Texas Hispanics, percent of the population which is diabetic and percent which is overweight, are also consistent with the New World Syndrome. Expected patterns of disease in males vs females are also confirmed. Factors that do not support the New World Syndrome hypothesis and can be examined by future studies are described. This is the first report since the original describing and updating patterns of middle digestive cancers in Texas Hispanics as resulting from the New World Syndrome. Application of these findings to contemporary medical practice and to cancer prevention are reviewed.

Asian People↗

Immunoglobulin G antibody avidity in patients with respiratory syncytial virus infection.

The titer and avidity of respiratory syncytial virus-specific antibodies were measured in 196 serum specimens from 93 children with an acute, laboratory-confirmed respiratory syncytial virus infection. An enzyme immunoassay method based on the ability of urea to dissociate the bound antibodies with low avidity from the antigen was used. Three patterns of immune responses were observed. Children less than 6 months of age usually had low titers of antibodies with high avidity in their acute-phase serum samples. These antibodies were concluded to be of maternal origin, since their reaction pattern was similar to that of healthy adults. During the next few weeks, a slight increase in titers with a concurrent decrease in antibody avidity was observed. All children 6 to 24 months of age had low-avidity antibodies in their acute-phase serum samples, which matured to high avidity during the follow-up. On the contrary, about half of the children greater than 24 months of age had high-avidity antibodies already in the acute-phase serum samples. We conclude that the former children were experiencing primary infections with respiratory syncytial virus and the latter were experiencing reinfections. All adults with remote immunity had antibodies with high avidity.

Adult↗

Macular electroretinograms to flicker and pattern stimulation in lamellar macular holes.

Steady-state macular (9 degrees x 9 degrees) electroretinograms in response to either sinusoidal flicker (focal electroretinogram) or counterphased sinusoidal gratings (pattern electroretinogram) were recorded in 14 patients with inner lamellar macular holes, in 4 patients with full-thickness macular holes and in 14 age-matched controls. Fourier analysis of focal and pattern electroretinograms yielded three main components: a first and a second harmonic to flicker, and a second harmonic to pattern. Recent evidence indicates that the first harmonic to flicker is of receptoral origin, whereas the flicker and pattern second harmonics represent, at least in part, the activity of different generators in the inner retina. When compared to controls, patients with inner lamellar holes showed significant amplitude reduction and phase delay for both flicker and pattern second harmonics, but not for the flicker first harmonic. Patients with full-thickness holes showed significant amplitude reduction also for the flicker first harmonic. These results indicate a prevalent functional involvement of the inner retina in lamellar macular holes, which can be clinically detected by evaluating focal and pattern electroretinogram second harmonics.

Adult↗

Early pattern recognition in severe perinatal asphyxia: a prospective MRI study.

On the basis of MRI examinations in 88 neonates and infants with perinatal asphyxia, we defined 6 different patterns on T2-weighted images: pattern A--scattered hyperintensity of both hemispheres of the telencephalon with blurred border zones between cortex and white matter, indicating diffuse brain injury; pattern B--parasagittal hyperintensity extending into the corona radiata, corresponding to the watershed zones; pattern C--hyper- and hypointense lesions in thalamus and basal ganglia, which relate to haemorrhagic necrosis or iron deposition in these areas; pattern D--periventricular hyperintensity, mainly along the lateral ventricles, i.e. periventricular leukomalacia (PVL), originating from the matrix zone; pattern E--small multifocal lesions varying from hyper--to hypointense, interpreted as necrosis and haemorrhage; pattern F--periventricular centrifugal hypointense stripes in the centrum semiovale and deep white matter of the frontal and occipital lobes. Contrast was effectively inverted on T1-weighted images. Patterns A, B and C were found in 17%, 25% and 37% of patients, and patterns D, E and F in 19%, 17% and 35%, respectively. In 49 patients a combination of patterns was observed, but 30% of the initial images were normal. At follow-up, persistent abnormalities were seen in all children with patterns A and D, but in only 52% of those with pattern C. Myelination was retarded most often in patients with diffuse brain injury and PVL (patterns A and D).

Asphyxia Neonatorum↗

The density distribution of gene loci over the genetic map of Escherichia coli: its structural, functional and evolutionary implications.

A quantitative analysis was carried out on the dispersion of gene loci over the E. coli genetic map. Therefore, the map was divided into regions characterized by an homogeneous gene density. This created a distribution pattern of gene loci that contained a symmetry axis located near to the origin of DNA replication. The pattern could be subdivided into a set of 22 functional domains containing gene loci whose products revealed a biochemical or functional relatedness. A correlation was found between the boundary positions of these domains and the distribution of F plasmid- and DNA insertion sites over the E. coli chromosome. The structural, functional and evolutionary implications of these findings are discussed.

Biological Evolution↗

[RAPD-PCR analysis of the variability of spring common wheat cultivar genomes and their androclinal double haploid form].

Based on RAPD-PCR analysis with 15 primers including those homologous to particular loci, the level of genetic polymorphism in the collection of spring common wheat genotypes and their androclinal double haploid (ADH) lines was determined. Intraspecific polymorphism of the original wheat forms was 20%. By the absence of polymorphism in the molecular patterns of ADH lines and original forms, it was shown that, under the conditions used, no genetic changes in the genomic DNA of spring common wheat in anther culture occurred. Thus, the technology of direct in vitro androgenesis does not lead to genome rearrangements and may be used for rapid production of pure lines of such a complex allopolyploid as spring common wheat.

Base Sequence↗

[Pseudoperiodic and paroxysmal electroencephalographic activities].

Periodic and paroxysmal EEG patterns are frequent and easily recognized. They often correlate with particular neurological or systemic conditions. We propose a reclassification and critical examination of these periodic EEG patterns by reviewing the original work presented by J. Gaches in this journal some thirty years ago. Periodic EEG activity is still classified by its localisation--generalised or focal--and by its periodicity--long or short. Periodic long-interval diffuse paroxysmal patterns are reported with rare pathologies such as SSPE, trypanosomiasis or intoxication with phencyclidine. Suppression bursts (SB) may be found in two main situations post-anoxic encephalopathies and drug-induced comas. Ohtahara syndrome is a very rare childhood epileptic syndrome with SB. Periodic short-interval diffuse pattern have been reported in Creutzfeldt-Jakob disease but also in toxic encephalopathies, such as lithium intoxication or as recently reported in acute Cefepime intoxication as well as with metabolic encephalopathies and rarely during AIDS. Periodic lateralized epileptiform discharges (PLEDs) have been classified according to their morphology and the associated condition (epileptic seizures, subtle status, "vascular" seizure). The principal etiology is cerebro-vascular disease and herpes encephalitis but it has also been reported in several other neurological diseases.

Animals↗

High intercontinental migration rates and population admixture in the sapstain fungus Ophiostoma ips.

Ophiostoma ips is a common fungal associate of various conifer-infesting bark beetles in their native ranges and has been introduced into non-native pine plantations in the Southern Hemisphere. In this study, we used 10 microsatellite markers to investigate the population biology of O. ips in native (Cuba, France, Morocco and USA) and non-native (Australia, Chile and South Africa) areas to characterize host specificity, reproductive behaviour, and the potential origin as well as patterns of spread of the fungus and its insect vectors. The markers resolved a total of 41 alleles and 75 haplotypes. Higher genetic diversity was found in the native populations than in the introduced populations. Based on the origin of the insect vectors, the populations of O. ips in Australia would be expected to reflect a North American origin, and those in Chile and South Africa to reflect a European origin. However, most alleles observed in the native European population were also found in the native North American population; only the allele frequencies among the populations varied. This admixture made it impossible to confirm the origin of the introduced Southern Hemisphere (SH) populations of O. ips. There was also no evidence for specificity of the fungus to particular bark beetle vectors or hosts. Although O. ips is thought to be mainly self-fertilizing, evidence for recombination was found in the four native populations surveyed. The higher genetic diversity in the North American than in the European population suggests that North America could be the possible source region of O. ips.

Alleles↗

Staphylococcus aureus strains of the 94/96 complex isolated in the German Democratic Republic: incidence and discrimination of strain clones.

The incidence of S. aureus with a phage pattern of 94/96 rose from 9% in 1979 to 18% in 1985. The frequency of occurrence not only increased among isolates from inpatients and outpatients but also among those from healthy carriers. All of the 504 investigated strains of different origin exhibited a uniform pattern of biochemical characteristics. In each of 40 investigated strains, a plasmid with a molecular mass of 16 Md was found. Elimination experiments indicated that these plasmids determined resistance to penicillin and/or cadmium. Resistance to chloramphenicol was found to be determined by plasmids of 2.0 Md, resistance to oxytetracycline by plasmids of 2.7 Md. Clones could be discriminated by means of 7 experimental phages. The application of these phages for typing strains from infections in hospitals is demonstrated.

Bacteriophage Typing↗

The distribution of corticotectal projection neurons correlates with the interblob compartment in macaque striate cortex.

While much attention has been given to the correlation between cytochrome-oxidase (CO) compartments and patterns of cortico-cortical projections originating from supragranular layers in the striate cortex, little is known in this regard about patterns of cortico-subcortical projections originating from infragranular cortex. We studied the tangential distribution of the striate cortex neurons projecting to the superior colliculus and used two approaches to analyze the relationship of this distribution to the arrangement of CO "blobs." First, chi-square analysis indicated that significantly fewer labeled neurons were found within the CO blob compartment than the number expected for a random distribution. Second, spatial cross-correlation analysis--which circumvents the inherent subjectivity of delineating blob boundaries--revealed an area around blob centers in which there was a decreased probability of encountering labeled cells. The size of this area compared well with that of our outlines of CO blobs. We conclude that corticotectal projection neurons in the striate cortex are distributed preferentially within the interblob compartment of the infragranular striate cortex. These results demonstrate that the spatial distribution of cortico-subcortical projection neurons within infragranular cortex can correlate with the CO architecture of the primary visual cortex.

Animals↗

Alcohol-related disorders in first- and second-generation immigrants in Sweden: a national cohort study.

AIMS: The risk of alcohol-related disorders in first- and second-generation immigrants in Sweden were investigated and compared with the Swedish majority population to assess how alcohol habits are modified over generations in a new society. DESIGN: Register study based on multivariate analyses of demographic data, including information on country of birth, from the Swedish Population and Housing Census of 1985 linked to data on hospital admissions for alcohol-related disorders during 1990-99 in the National Hospital Discharge Register. PARTICIPANTS: The study population consisted of a national cohort of 1.25 million youth born 1968-79 and 1.47 million adults born 1929-65. RESULTS: First- and second-generation immigrants from Finland had higher relative risks (RRs) for hospital admission because of an alcohol-related disorder compared to the Swedish majority population (socio-economic adjusted RRs 2.1 and 1.9, respectively), while first-generation immigrants born in southern Europe, the Middle East and other non-European countries had lower risks. Second-generation immigrants with heritage in southern Europe, the Middle East and other non-European countries had socio-economic adjusted RRs that were higher relative to the first generation immigrants but lower relative to the Swedish majority population. Intercountry adoptees had the highest adjusted RR (2.5). CONCLUSIONS: Patterns of alcohol abuse in the country of origin are strong determinants of alcohol-related disorders in first-generation immigrants. The patterns in second-generation immigrants are influenced by parental countries of origin as well as patterns in the majority population. The Finnish minority and intercountry adoptees are of particular concern in prevention.

Adult↗

Mammographic parenchymal patterns as indicators of breast cancer risk.

Mammographic parenchymal patterns have been suggested as indicators of breast cancer risk. However, few well-controlled studies have used prediagnostic mammograms to determine the pattern classification. The authors studied 266 cases of breast cancer and 301 controls from 25 screening centers of the Breast Cancer Detection and Demonstration Project, a nationwide screening program conducted between 1973 and 1980 to evaluate the risk associated with mammographic patterns using mammograms taken four years before the detection of breast cancer. Mammograms of the cancerous breast of cases and of the ipsilateral breast in the control matched to each case were blindly assessed by one of the investigators (J.N.W.), originator of the mammographic pattern classification. The breast cancer odds ratio among women with the combined P2 + DY patterns, compared with women with the N1 pattern, was 2.8 (95% confidence interval (CI): 1.6-5.1). This estimate of relative risk was comparable with the risk associated with other recognized breast cancer risk factors. The odds ratio among P2 + DY women with a first-degree family history of breast cancer was 5.5 (95% CI: 2.6-11.8) compared with N1 women without a family history. These data provide additional evidence that mammographic patterns are indicators for subsequent development of breast cancer, particularly among women with a first-degree family history of this malignancy.

Adult↗

Inhibitor production by group-G streptococci of human and of animal origin.

Strains of group-G streptococci were tested by a "fingerprinting" method for the production of (P typing) and sensitivity to (S typing) inhibitory agents, and were biotyped. In the standard P-typing test, 28 of 50 strains of human origin, but none of 30 strains of animal origin, showed inhibitory activity. Of the human strains, 12 formed a bacteriocin that was active on group-A streptococci, including three (strains I2, I5 and I8) of the four streptococci of this group among the indicator strains. Sixteen other human strains inhibited the fourth group-A indicator (strain I7), and to a lesser extent strain I2, by lowering the pH of the typing medium. This acid-mediated inhibition was eliminated by testing on a medium containing calcium carbonate 0.5%; the 16 strains were then completely non-inhibitory, and the bacteriocin-forming strains, the typing pattern of which had originally been I2, I5, I7, I8, showed only inhibition attributable to the action of the bacteriocin. Nearly all group-A streptococci were sensitive to the group-G bacteriocin. The indicator strain I7 and several other members of M-type 28 were exceptions, but their resistance was not associated with the presence of R-antigen 28. Fifteen inhibitor-sensitivity patterns and 12 biotypes were identified among the strains; some of these tended to be associated with either a human or an animal origin. Neither S type nor biotype appeared to correlate with inhibitor production.

Animals↗