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Biomedical subjects

J German

Publications and source records attributed to J German.

At least 73 records · Page 4Linked to original sources
PubMed1984

Werner's syndrome: proliferation in vitro of clones of cells bearing chromosome translocations.

Each of several cultures of Werner's syndrome (WS) fibroblasts and lymphoblasts examined was found to be composed of one or several clones of cells with mutated chromosome complements. Two "sister" fibroblasts cell lines (FCLs) that were derived from a mixture of explants cut from the same WS skin biopsy were found to have completely different rearranged chromosome complements. Daily observation of the skin explants from which these two sister FCLs were derived revealed not only that no more than a few fibroblasts ever migrated from a given explant but also that fibroblasts migrated from only a few of the explants. Two of three lymphoblastoid cell lines (LCLs), each probably developed as an independent clone from a different cell from the same WS blood sample, were mosaic, comprised of cells having both normal and rearranged chromosome complements. The third LCL studied, although nonmosaic, had a rearranged chromosome complement, but one that was completely different from those in the other two lines. Based on the observations described, hypotheses have been formulated to explain both the preponderance in long-term WS cultures of clones with mutated chromosome complements and the abbreviated lifespan characteristic of WS fibroblast cultures.

Adult↗
PubMed1983

Bloom's syndrome: evidence for an increased mutation frequency in vivo.

The incidence of lymphocytes resistant to the purine analog 6-thioguanine was studied in seven patients with Bloom's syndrome. The mean frequency was 17.3 X 10(-4). The mean incidence in age- and sex-matched controls was 2.1 X 10(-4), so approximately eight times the normal number of 6-thioguanine-resistant lymphocytes were detected in Bloom's syndrome blood. The basis for this increase is unknown, but the inherent genomic instability demonstrated in the form of chromosomal aberrations is one possible explanation.

Bloom Syndrome↗
PubMed1983

Bloom's syndrome cells have an abnormal serum growth response.

Certain growth responses of Bloom's syndrome (BS) dermal fibroblasts have been compared to those of normal human fibroblasts. By applying the principles of Michaelis-Menton kinetics to clonal dose-response data, serum and epidermal growth factor (EGF) requirements of the two cell types were found to be similar. However, the maximal clonal growth rate of BS cells was significantly lower than that of their normal counterparts. Although specific EGF binding by BS cells was marginally higher than in normal cells, EGF's growth-promoting activity was only half of that seen in normal cells. These observations indicate that the abnormally low growth rate of BS cells is not attributable to excessive requirements for serum-derived growth factors and suggest instead that the genetic defect in some way impairs the cells' ability to respond fully to growth stimulation.

Adult↗
PubMed1983

Familial predisposition to cancer and age at onset of disease in randomly selected cancer patients.

Incidence of malignancy among close relatives was used to evaluate the relationship of early age at diagnosis and familial cancer predisposition in a general population of cancer patients. The occurrence of cancer and other conditions in families of more than 1,350 randomly selected patients with a wide variety of malignancies was ascertained. Each patient was assigned to one of four study groups based on comparison of his age at diagnosis with the distribution of ages at diagnosis for his cancer site compiled by the Third National Cancer Survey. These groups consisted of patients whose ages at diagnosis were in: (1) the lowest decile, (2) the median decile, (3) above the median decile, and (4) between the lowest and median deciles. Person-years and calendar time at risk were calculated for first-degree relatives in each group. The numbers of cancers expected among these relatives were calculated using age- and time-specific incidence rates of a standard population. Statistical analysis of (1) the numbers of reported vs. expected cancers in relatives and (2) the numbers of families reporting cancer in parents or siblings of patients showed that a familial tendency to develop cancer exists in this randomly selected population of cancer patients, regardless of age at onset of malignancy in the proband. Conversely, early age at diagnosis of cancer may indicate genetic predisposition to malignancy only in exceptional cases.

Adolescent↗
PubMed1981

Xeroderma pigmentosum patients from Egypt: II. Preliminary correlations of epidemiology, clinical symptoms and molecular biology.

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.

Adult↗
PubMed1980

Chromosome-breakage syndromes: different genes, different treatments, different cancers.

Comparison of the strikingly different distributions of types of cancer that occur in the genetic disorders that feature chromosome instability raises several interesting points. (a) Bloom's syndrome: the distribution suggests that many of the cancers that occur with regularity in the general population just occur more commonly and at an earlier age. (b) Ataxia telangiectasia: cancers of many types are increased in frequency, but lymphoreticular cancers are exceptionally common, the case also in several other genetically determined immunodeficiency disorders. Both Bloom's syndrome and ataxia telangiectasia share defective immunity as a major clinical feature, but the respective roles, if any, of it and of chromosome instability in producing the cancer predispositions are unknown. (c) Fanconi's anemia: cancer apparently has become common only recently. The types and distribution which occur are unusual. Fanconi's anemia cells have been shown to be hypertransformable by oncogenic virus and to be defective in handling certain types of DNA damage (as well as to manifest chromosome instability) so that the recent increase in cancer incidence is both surprising and unexplained. The degree of cancer proneness of Fanconi's anemia per se, untreated by modern methods, must at present be considered unknown. (d) Xeroderma pigmentosum: the cancer predisposition apparently extends only to cells which receive solar damage, i.e., to skin and eye. This would not have been predicted in view of the fact that the cellular mechanism is defective for repairing DNA damage produced not just by sunlight but also by certain classes of chemical carcinogens.

Anemia, Aplastic↗
PubMed1980

Analysis of a BrdU-sensitive site in the cactus mouse (Peromyscus eremicus): chromosomal breakage and sister-chromatid exchange.

When the thymidine analog BrdU was incorporated into the DNA of a fibroblast cell line derived from the cactus mouse Peromyscus eremicus, a chromosome region with an increased frequency of gaps and breaks was observed. Nearly a third of the chromatid aberrations found at this site were associated with a sister-chromatid exchange (SCE) although this chromosome region showed no increase in sister-chromatid exchange in the absence of a gap or break. SCEs were significantly decreased in the remainder of the chromosome arm when it contained an aberration at the unstable site. This BrdU-sensitive region, unlike others reported, was found not to be late-replicating.--In this chromosome complement, the frequency of sister-chromatid exchange in C-band positive regions was significantly lower than that in C-band negative regions.

Animals↗
PubMed1980

Xeroderma pigmentosum, defective DNA repair--and schistosomiasis?

Xeroderma pigmentosum (XP) is more common in Japan and Egypt than in Europe and America. Some unidentified selective advantage for the carrier of an XP gene is the probable explanation for these regional increases. The question then arises as to what unusual environmental factor(s) Japan and Egypt, otherwise so disparate, might share that is not shared by most of the Western World. The dependence on flooded lands for crop production is one such feature, and human schistosomiasis has been a consequence in both places. The second question becomes, therefore, how might this parasitism be responsible for an increased frequency of XP genes? Schistosomal cercariae, being phototropic, may be assumed to suffer considerable sunlight damage to their DNA immediately before they penetrate the integument of some vertebrate. The hypothesis is advanced that they obtain assistance from their vertebrate host in repairing this damage. Should that be the case, a host less proficient than normal at providing such assistance--as the XP heterozygote might be--, would promote the survival and maturation of relatively few parasites, and thus resist the general debility associated with heavy adult-worm burdens. In a broader sense, the hypothesis suggests that a host can acquire a degree of resistance to a parasite as result of a mutation that affects some essential biochemical mechanism in which the parasite depends on the host for assistance.

DNA Repair↗
PubMed1979

Sensitivity of Bloom's syndrome lymphocytes to ethyl methanesulfonate.

Ethyl methanesulfonate induced several times as many sister chromatid exchanges (SCE's) in lymphocytes from individuals affected with Bloom's syndrome as in lymphocytes from controls or heterozygotes. In cultures of cells from an individual with Bloom's syndrome who had two populations of lymphocytes circulating in his blood--'low' cells having normal spontaneous frequencies of SCE's and 'high' cells having elevated frequencies--only the high cells showed the increased sensitivity to ethyl methanesulfonate.

Cells, Cultured↗
PubMed1979

Roberts' syndrome. I. Cytological evidence for a disturbance in chromatid pairing.

In the rare developmental disorder Roberts' syndrome, prophase and metaphase chromosomes display premature sister-chromatid separation, most prominently at certain regions in which the chromatin is composed of highly reiterated base sequences. In addition, interphase nuclei present a striking distortion in their contours. The observed abnormalities are interpreted as evidence for the presence of a genetically determined disturbance affecting the normal mechanisms for pairing and disjoining of sister chromatids.

Abnormalities, Multiple↗
PubMed1979

Bloom's syndrome. VII. Progress report for 1978.

The Bloom's Syndrome Registry was published in this journal in 1977. Now, in the first in a series of progress reports, recent accessions to the Registry are recorded, new instances of neoplasia are listed, and recent clinical observations and experimental results of general interest are cited.

Abnormalities, Multiple↗
PubMed1979

Human male infertility, probably genetically determined, due to defective meiosis and spermatogenic arrest.

A family is reported in which infertility affected three men related through their mothers. The propositus, from testicular tissue was obtained, exhibited desynapsis, lack of chiasmata, and degeneration of spermatocytes during the first meiotic division. These observations lead us to postulate that a gene for meiotic disturbance, spermatogenic arrest, and azoospermia is segregating in this family; its mode of inheritance conforms to either an X-linked recessive or a sex-limited autosomal dominant transmission.

Adult↗