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Biomedical subjects

L Atkins

Publications and source records attributed to L Atkins.

At least 37 records · Page 2Linked to original sources
PubMed1986

Quiescent human diploid fibroblasts. Common mechanism for inhibition of DNA replication in density-inhibited and serum-deprived cells.

The mechanism for cessation of proliferation in density-inhibited quiescent human diploid fibroblasts (HDF) and serum-deprived quiescent HDF was compared in two ways. Density-inhibited HDF were fused to either replicating HDF or SV40-transformed HDF and DNA synthesis was measured in the resulting heterokaryons. DNA synthesis was inhibited in the replicating HDF nuclei in heterokaryons in a way that suggested that entry into S phase was blocked, but ongoing DNA synthesis was not inhibited. In contrast, DNA synthesis was induced in the quiescent nuclei in heterokaryons formed with SV40-transformed HDF. Previous experiments had shown that serum-deprived HDF also behave in this way in heterokaryons. To test this similarity further, we examined the inhibitory activity of cell membranes prepared from both types of quiescent HDF. We found that both types of quiescent HDF contain DNA synthesis-inhibitory activity that is (1) effective on replicating HDF; (2) ineffective on SV40-transformed HDF; (3) sensitive to heat and trypsin. Thus, these results support the hypothesis that both density-inhibited HDF and serum-deprived HDF share a common mechanism for arrest in G1 phase. They also suggest that a membrane-bound protein plays a role in the inhibition of DNA synthesis in quiescent HDF.

Blood↗
PubMed1986

Membrane-associated inhibitor of DNA synthesis in senescent human diploid fibroblasts: characterization and comparison to quiescent cell inhibitor.

Cell membranes prepared from senescent human diploid fibroblasts (HDF) inhibited entry into S phase by 35% when added to the medium of replicating young HDF. This membrane-associated inhibitory activity was (i) sensitive to trypsin, heat, and periodate, which suggests that the inhibitor is a glycoprotein, and (ii) not able to inhibit DNA synthesis in simian virus 40-transformed HDF, which indicates that not all types of cells are sensitive to this inhibitor. Quiescent young HDF also have a surface membrane-associated inhibitor of DNA synthesis. A comparison of the senescent HDF and quiescent HDF inhibitor activities indicates that they may have the same chemical and physical nature and the same specific activity, but their regulation is different. The inhibitory activity of quiescent young HDF is abolished within 20 hr after refeeding with fresh serum-containing medium, whereas that of senescent HDF remains unchanged. Quiescent old HDF (two or three population doublings remaining) exhibit an intermediate response to serum with approximately two-thirds of the inhibitory activity abolished. The fraction of cells in S phase at 20-24 hr post-stimulation (37% in young HDF, 24% in old HDF, and 0% in senescent HDF) is inversely proportional to inhibitor levels. This suggests that inability to neutralize the inhibitory activity in response to serum stimulation could be involved in the inability of senescent HDF to enter S phase. Disappearance of the inhibitory activity from quiescent young HDF occurs late in G1 phase. Thus, the inhibitor may play a role in determining the length of the G0 to S phase transition in these cells.

Cell Cycle↗
PubMed1984

KLE: a cell line with defective estrogen receptor derived from undifferentiated endometrial cancer.

KLE is a cell line derived from a poorly differentiated endometrial carcinoma that is aneuploid with chromosome numbers ranging from 51 to 66 and 6-8 marker chromosomes demonstrated by G banding. Tumors harvested from five of five nude mice bearing an inoculum for more than a month resemble the original specimen, and electron microscopy shows microvilli, many junctional processes, glycogenation, and a prominent nucleolonema. The cell cytosol contains a specific binder for estradiol, but there is no estrogen receptor in the nucleus and in a study reported elsewhere (Raam et al., Breast Cancer Res. Treat. 2, 277 (1982) ) translocation to the nucleus fails to occur. The enzyme phenotype of this cell is human, non-HeLa.

Adenocarcinoma↗
PubMed1982

Dysgenesis of testicular and streak gonads in the syndrome of mixed gonadal dysgenesis: perspective derived from a clinicopathologic analysis of twenty-one cases.

The clinical and pathologic aspects of 21 cases of mixed gonadal dysgenesis (MGD) were studied. The gonads in 15 patients consisted of a macroscopic testis and a streak gonad; six patients had variants, including two with bilateral testes and four with bilateral streak gonads or tumors. Functionally, the gonads were incompetent. Testes 1) failed to completely inhibit müllerian development, 2) failed to support full differentiation of mesonephric duct structures, 3) failed to adequately masculinize development of the external genitalia, or 4) often failed to mediate their own descent, resulting in asymmetry of the internal and external genitalia. None of the streak gonads mediated normal female adolescent development or fertility. Microscopic examination revealed that every gonad, regardless of its gross appearance, was morphologically abnormal. Although gonads with seminiferous tubules usually developed to a moderately advanced state, macroscopically resembling testes, the hilar zone remained architecturally disorganized; the cortex invariably lacked more than a rudimentary tunica albuginea or exhibited partial ovarian differentiation, sometimes even with a rare primordial follicle. Over time, the seminiferous tubules atrophied and hyalinized. Gonads that grossly resembled streak gonads were observed microscopically to be composed of a stroma resembling that of normal ovarian cortex. In patients more than several years of age, the entire complement of germ cells in streak gonads disappeared. It is suggested that patients with MGD be raised as females. Early removal of gonads will prevent the development of gonadoblastoma and dysgerminoma. If the uterus is retained and the patient is subsequently given exogenous estrogen, care should be taken to detect early any signs of the development of endometrial carcinoma or its precursor, to which these patients may be prone.

Adolescent↗
PubMed1980

Learning disorders and sex chromosome aberrations.

No sex chromosome aberrations were detected in a prospective study of twenty adult dyslexic men. A retrospective study of eighty-nine subjects with known sex chromosome aberrations revealed twenty of them to be mentally-retarded. Among the sixty-nine subjects of normal intelligence, learning, speech and attention disorders were frequent. Children with 47,XYY, 47,XXY, and 47,XXX karyotypes appeared particularly prone to experience delays in speech development as well as later academic underachievement in language-related subjects. In contrast, speech development was normal in all of the girls with Turner's syndrome and later academic difficulties were usually confined to mathematics or science. Hyperactivity was noted with considerable frequency among 47,XYY and Turner's syndrome subjects, but not among subjects with a 47,XXX or 47,XXY karyotype.

Adolescent↗
PubMed1980

A clinical syndrome associated with 5p duplication and 9p deletion.

We have evaluated a sister and brother with a similar pattern of malformations and death in early childhood associated with partial duplication chromosome 5p and possibly deletion of 9p. The father and the brother and several paternal relatives are carriers of the balanced translocation t(5;9) (p13;p22). The malformations which the two have in common are: prominent forehead, flat nasal bridge, long thin fingers, bilateral equinovarus deformity of the feet, diaphragmatic hernia and kidney malformations. The children died at ages 4 months and 27 months, the latter showing marked psychomotor retardation. The chromosome abnormalities, clinical history, and phenotypic features of our patients are similar to the case reported by Monteleone et al (1976). The findings in our patients and Monteleone et al. (1976) are not similar to those in other reported cases of partial and complete 5q duplications, perhaps because the others do not have partial deletion of 9p.

Abnormalities, Multiple↗
PubMed1979

Eosinophilia, chloromas and a chromosome abnormality in a patient with a myeloproliferative syndrome.

The existence of eosinophilic leukemia remains controversial since many authors challenge the existence of this entity. We present a patient with a hypereosinophilic syndrome whose findings were consistent with a leukemic process. The patient's course was marked my signs and symptoms of myeloblastoma formation and his illness terminated in an acute blastic crisis. chromosome studies on peripheral blood leucocytes demonstrated aneuploidy and an abnormal number four chromosome with additional material on its long arm. This case appears to be an unusual example of a hypereosinophilic syndrome with both myeloblastoma formation and an abnormal leucocyte karyotype.

Adult↗
PubMed1979

Multiple congenital anomalies/mental retardation (MCA/MR) syndrome due to partial 1q duplication and possible 18p deletion: a study of four individuals in two families.

We have evaluated four individuals from two unrelated families with a similar multiple congenital anomalies/mental retardation (MCA/MR) syndrome due to partial duplication of chromosome 1q and possible deletion 18p. In both families the mothers and several relatives were carriers of the balanced translocation rcp t(1;18) (q42;p11). The features which the four have in common are relative macrocephaly, prominent forehead, micrognathia, and highly arched palate; three of the four individuals have short stature, scoliosis, kyphosis, hirsutism, camptodactyly, sacral dimple, repaired inguinal hernias, and eye abnormalities. Reproductive histories of five balanced translocation carriers in these families indicate that they have a high risk of spontaneous abortions and infants with multiple malformations.

Abnormalities, Multiple↗
PubMed1979

Aniridia-Wilms' tumor association: evidence for specific deletion of 11p13.

A 7-year-old boy with aniridia, Wilms' tumor, and mental retardation, previously reported as having an interstitial deletion of the short arm of chromosome 8 resulting from a t(8p+;11q-) translocation (Ladda et al., 1974), has been restudied using high-resolution trypsin-Giemsa banding of prometaphase chromsomes. The results revealed a complex rearrangement with four break points in 8p, 11p, and 11q, leading to a net loss of an interstitial segment of 11p (region p1407 yields p1304) but not of 8p. His red blood cells contained normal activities of glutathione reductase (gene on 8p) and lactate dehydrogeanse A (gene on 11p12), indicating a gene dosage consistent with the chromosomal findings. The revised interpretation of this case agrees with seven others reported as having aniridia and interstitial 11p deletions in establishing the distal half of band 11p13 as the site of gene(s) which lead to aniridia and predispose to Wilms' tumor if present in a hemizygous state. Possible relationships between heterozygous deletion of specific chromosomal bands 11p13 and 13q14 and the autosomal dominant disorders aniridia, Wilms' tumor, and retinoblastoma, respectively, are discussed.

Abnormalities, Multiple↗
PubMed1979

Loss of Rh antigen associated with acquired Rh antibodies and a chromosome translocation in a patient with myeloid metaplasia.

Myeloid metaplasia is a clonal disease of the marrow pluripotent stem cell in which a constant cytogenetic abnormality could result in an altered antigenic characteristic of hematopoietic cells. A 57-yr-old man who had acquired myeloid metaplasia at age 37 was noted to be Rh negative, although blood typing at age 33 was Rh positive. His erythrocytes reacted with anti-c and anti-e, typical for an Rh negative individual. Analysis of 11 metaphase bone marrow cells by G-banding revealed 46 chromosomes with a consistent anomaly in 100% of cells involving chromosomes 1 and 13. The changes were consistent with a reciprocal translocation, with break points at approximately 1p32 and 13q22, although break points at 1p13 and 13q14 were also possible. Since previous cytogenetic data have localized the Rh gene to the short arm of chromosome 1, our data indicate the Rh gene lies within the segment u13 leads to 1p32. Serum of this patient had circulating anti-D and anti-C antibodies. Consequently, this patient lost immunologic tolerance to a "self antigen" after losing the ability to express this antigen.

Chromosome Mapping↗
PubMed1978

Down syndrome in two of three triplets.

This is the first report to our knowledge of trisomy 21 in two members of a set of triplets. The two with Down syndrome are monozygous; the other triplet is not identical. These triplets were born to a 22-year-old woman in whose family there have been six sets of twins (four like-sex) since 1775. Neither parent has any chromosomal abnormality. Zygosity estimates in the triplets are derived from studies of red blood cell antigens and HLA typing. Twinning has been reported in association with many different chromosome abnormalities. It has been suggested that the incidence of Down syndrome among twins is significantly higher than among singletons. It seems likely that some families have a heritable predisposition to both twinning and chromosome abnormalities.

Chromosome Banding↗
PubMed1978

Chromosome 6q- and associated malformations.

A dysmorphic retarded fourteen-mont-old female with partial deletion of the long arm of chromosome 6 is presented. The breakpoint in 6q was in region 2, probably at band 5. Eight other infants with a deletion involving the long arm of chromosome 6, including five with a ring chromosome 6, have been reported. The affected individuals have in common microcephaly, micrognathia, hypotonia and psychomotor retardation, but do not appear to have a distinctive phenotype.

Abnormalities, Multiple↗
PubMed1977

Tissue culture studies in Hodgkin's disease: Morphologic, cytogenetic, cell surface, and enzymatic properties of cultures derived from splenic tumors.

Monolayer and suspension cell cultures prepared from Hodgkin's disease tumors in the spleen were examined microscopically and by cytogenetics, tested for lymphocyte and monocyte cell surface properties, and assayed for enzymes by histochemical and spectrophotometric techniques. Hodgkin's disease monolayer cultures were composed of rapidly proliferating round and polygonal cells that were capable of propagation in vitro for an indefinite period of time. Abnormal aneuploid chromosomes were found in short-term Hodgkin's disease monolayers that had been passaged 16-20 times, and in established cell lines carried in culture longer than 3 yr and passaged more than 200 times. Cells fromHodgkin's disease monolayers contained lysozyme (muramidase), fluoride-resistant alpha naphthol acetate esterase, acid and alkaline phosphatase, and chymotrypsin-like activity. The monolayers did not exhibit specific cell surface markers or phagocytosis. Suspension cultures derived from Hodgkin's disease monolayers were composed of cells with aneuploid karyotypes and similar enzymes. The Hodgkin's disease suspension culture cells had surface receptors for complement and IgGFc, lacked surface or cytoplasmic immunoglobulin, and did not form Erosettes, react with an antithymocyte serum, nor exhibit phagocytosis. Normal monolayer culture cells, derived from adult spleen and human fetal spleen and thymus, were composed of spindle cells with a diploid number of chromosomes that could be carried for only a finite period of time in vitro. Normal cultured cells contained similar esterases and phosphatases, but were devoid of lysozyme and chymotrypsin-like activity. The morphologic, cytogenetic, cell surface, and enzymatic findings indicate that our Hodgkin's disease monolayer and suspension cultures are composed of cells with many properties suggesting an origin from monocytes (macrophages) rather than lymphocytes or fibroblasts. The presence of aneuploid karyotypes is consistent with a neoplastic origin and derivation from a malignant cell of Hodgkin's disease.

Alkaline Phosphatase↗
PubMed1977

Gene mapping by fluorescent in situ hybridization.

We describe a new method for the mapping of mammalian genes, utilizing in situ hybridization of mRNA to DNA of chromosomes. It involves the hydrogen bonding of the polyadenylic acid at the 3' end of hybridized mRNA to the polyuridylic acid tail of a highly fluorescent latex microsphere. The resultant double hybrid can be visualized by fluorescence microscopy. The chromosomal localization of human alpha + beta globin genes has been explored by this method. Our data point ot the long arms of chromosomes 4 and 5 as the loci for the human globin genes.

Chromosome Mapping↗
PubMed1976

Etiologic heterogeneity of neural-tube defects.

We classified 106 stillborn and live-born infants with anencephaly, meningomyelocele, meningocele and encephalocele according to the recognized causes of these malformations. Six different causes were identified, including both genetic and nongenetic disorders; 12 per cent had nongenetic disorders, a chromosome abnormality, or an encephalocele as part of the autosomal recessive Meckel syndrome. Therefore, for this 12 per cent genetic counseling normally provided for isolated anencephaly, meningomyelocele or encephalocele would have been incorrect. If all infants were considered together regardless of cause, the precurrence and recurrence rates of similar malformations in the sibs were 5.2 and 1.7 per cent respectively. However, if infants with other disorders, especially the Meckel syndrome, were excluded, the precurrence and recurrence rates for isolated anencephaly, meningomyelocele and encephalocele among white infants were only 1.7 per cent and 0 per cent. These rates are much lower than the risk of 5 per cent currently being used in genetic counseling in the United States.

Abnormalities, Multiple↗