Glycoproteins expressed on human tumor cell membranes.
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Cell Membrane↗
Biomedical subjects
F Gilbert
Publications and source records attributed to F Gilbert.
In vitro and in vivo growth characteristics of two different cell populations in an established line of human neuroblastoma.
Two distinct cell morphologies were appreciated and separated in a long-established culture line (CHP-100) of human neuroblastoma. Both cell types carried chromosomal markers characteristic of neuroblastoma cells and the parent line; in addition, separate karyotypic changes in each cell type established them as separate and enriched populations. A small, refractile cell, designated CHP-100-S, was present and formed numerous cytoplasmic processes. A distinctly larger cell, CHP-100-L, was less refractile and lacked processes. The two cell types exhibited marked differences in adhesive properties in vitro. CHP-100-L adhered tightly to the culture flask and required enzymatic treatment for removal; CHP-100-S adhered loosely and could be harvested into the medium by simply tapping the flask. These two harvesting procedures were used to obtain highly enriched populations of each cell type, both of which proved to be tumorigenic in the nude mouse. In vitro, no significant difference in growth rates was observed between CHP-100-S (doubling time, 26 hr) and CHP-100-L (21 hr). However, in the nude mice, following inoculation of equal cell numbers, CHP-100-L cells grew much larger tumors than did CHP-100-S cells (3- to 100-fold increases over 25 days). Local invasion was also noted more frequently with the CHP-100-L explants. Reculturing of the mouse explants showed that the distinct cell morphologies were maintained even after multiple passages. The presence of heterogeneous cell populations in single tumors is of much potential importance for the clinical and biological behavior of neoplasms. The present data establish cultured human neuroblastomas as one model for studies of cell heterogeneity and suggest potentially important ramifications for the different cell types observed in the growth patterns of this neoplasm.
Animals↗
Abnormalities of chromosome #13 in retinoblastomas from individuals with normal constitutional karyotypes.
Constitutional chromosome abnormalities have been associated with retinoblastoma, Wilm's tumor, and a familial form of renal carcinoma. For each tumor type, the particular chromosome segment involved in the observed rearrangements is different: in retinoblastoma, that segment is band q14 on chromosome #13. We now present evidence that in retinoblastoma, structural abnormalities involving the particular chromosome segment identified in the constitutional cases can also occur in the tumors of individuals with normal constitutional karyotypes. Six cases with retinoblastoma in one or both eyes were analyzed; deletions/rearrangements involving 13q14 were found in the tumor cell karyotypes of five of the six. These observations suggest that changes in a gene or genes at a common site (13q14) play a role in tumorigenesis in all forms of retinoblastoma, sporadic as well as heritable.
Child, Preschool↗
Abnormalities of chromosome 1p in human neuroblastoma tumors and cell lines.
Specific constitutional chromosome rearrangements have been described in a small number of individuals with two solid childhood tumors, retinoblastoma and Wilms' tumor. On the basis of these observations, a causal relationship between these chromosome abnormalities and tumorigenesis has been postulated. Though a specific constitutional chromosome abnormality has yet to be reported in association with neuroblastoma, another childhood tumor, we now confirm the involvement of a particular chromosome segment in structural abnormalities in cells from this tumor. Deletions or rearrangements of chromosome 1p were found in preparations from four of six neuroblastomas from individuals with normal constitutional karyotypes and in three of four permanent neuroblastoma cell lines. Structural abnormalities resulting in the loss or rearrangement of material from 1p (with the most frequent break point being 1p32 and with all rearrangements involving the apparent loss or rearrangement of material distal to 1p31, always including 1p34 to 1pter), represent the single most common class of chromosome aberrations in neuroblastoma. This suggests that the distal portion of 1p contains at least one gene involved in the development of neuroblastoma.
Cell Line↗
Homogeneously staining regions in direct preparations from human neuroblastomas.
Previous descriptions of homogeneously staining regions in human neuroblastomas have been in karyotypes obtained from established cell lines. We now report homogeneously staining regions in direct preparations from two human neuroblastomas. In one of the cases, the homogeneously staining region identified in the primary tumor was also found in metastases to bone marrow and pleural fluid. The homogeneously staining region is, therefore, not an artifact of growth in vitro.
Bone Marrow↗
A deleted chromosome no. 13 in human retinoblastoma cells: relevance to tumorigenesis.
In this report of banded karyotypes prepared after short-term culture (72 hr) from human retinoblastoma tumor tissue, on del(13)(pter leads to q14:) chromosome and one normal chromosome #13 were found in all of the metaphases examined. Similar deletions (always involving 13q14) have previously been described in the somatic cells of individuals with one form of retinoblastoma. In the present case, however, the constitutional karyotype is normal. The presence of tumors in both eyes suggests that this is the genetic form of retinoblastoma, even though the patient's family history is negative for this tumor. The normal constitutional karyotype argues that the chromosome deletion occurred as a postzygotic event. The modal chromosome number of the tumor cells is 47 and rearrangements involving chromosomes #2, #17, and #20 were also identified.
Child, Preschool↗
Homogeneously staining region in a retinoblastoma cell line: relevance to tumor initiation and progression.
A human retinoblastoma cell line was found to contain a homogeneously staining region (HSR) on chromosome 1 (at 1p34). An HSR had previously been identified at the same site in a human neuroblastoma cell line. Of the original retinoblastoma line, a subpopulation was found which did not contain the 1pHSR but did contain a 3p+ chromosome in which the additional segment resembled a small HSR. The 3p+ was most likely the result of the translocation between the 1pHSR and the short arm of a chromosome 3. Preliminary results also indicate that the retinoblastoma cells with the 1pHSR produced tumors in athymic nu/nu mice in an average of 28 days, while identical numbers of the retinoblastoma cells with the 3p+ (probable HSR) produced tumors in an average of 75 days.
Cell Line↗
Hybrid myelomas producing antibodies against a human neuroblastoma antigen present on fetal brain.
Spleen cells from mice immunized with a cultured human neuroblastoma were hybridized with the mouse plasmacytoma P3X63Ag8. Hybrid myelomas were screened for production of antibodies that reacted with human neuroblastomas but not with cells from other tissues. One of these hybridoma antibodies reacted with an antigen present on the six human neuroblastomas tested, one of two retinoblastomas, a glioblastoma, and fetal brain, but did not react with other tumors or tissues including adult human brain.
Antigens, Neoplasm↗
Increased DNA content of HSR-marker chromosomes of human neuroblastoma cells.
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Cell Line↗
Factors associated with breast structure in breast cancer patients.
The breast duct patterns and radiographic density, or dysplasia, of 104 breast cancer patients in Hawaii were examined by mammography. The proportions of the four types of breast structure were analyzed for possible relation with age, menopausal state, height, weight, and race. Multiple regression analysis indicated that menopausal state appears to be more important than age per se for the general change in breast structure. Low body weight, but not race, is associated with prominent duct patterns and dysplasia.
Adult↗
Age at menopause in relation to reproductive history in Japanese, Caucasian, Chinese and Hawaiian women living in Hawaii.
A multiple regression analysis was undertaken to examine the relationship between age at menopause and selected biological and sociological variables in the reproductive history of Caucasian, Japanese, Chinese and part-Hawaiian post-menopausal women living in Hawaii. The analysis was conducted using the medical history records of 196 Caucasian, 181 Japanese, 72 Chinese and 60 Hawaiian women. Age at menarche, parity and months spent breast-feeding were found to have no significant effect on age at menopause. Regression models were not found to be heterogeneous among ethnic groups and no substantial interaction of ethnic group was found with age at menarche, parity or months spent breast-feeding.
Asian People↗
Double minute chromosomes and the homogeneously staining regions in chromosomes of a human neuroblastoma cell line.
Four human neuroblastoma cell lines were studied by chromosome banding techniques. All of the lines contained a marker chromosome with a long nonbanding homogeneously staining region (HSR). The HSR-containing chromosome differed in each line. One line contained two classes of cells: one with an HST marker chromosome and the other with double minute chromosomes. Each cell had one of these abnormalities; no cell had both. The presence of two additional chromosomal markers in all cells of this line indicates a common origin. These observations suggest that the double minute chromosomes are derived from the HSR.
Cell Line↗
Patterns of menopause: a study of certain medical and physiological variables among Caucasian and Japanese women living in Hawaii.
Comparisons were made between menopausal women and nonmenopausal controls among Caucasians and Japanese living in Honolulu, to investigate the extent of physical changes and clinical symptoms associated with menopause. The analysis was conducted using the multiphasic screening records of 170 menopausal cases and 162 nonmenopausal controls in Caucasians, and of 159 menopausal women and 187 nonmenopausal controls in Japanese. Discriminant function analysis was employed with relevant anthropometric, medical, and physiological variables. After adjusting for the linear and non-linear effects of age, only surgery and medication were retained as significant discriminant variables. Discriminant functions for Caucasian and Japanese groups were not found to be significantly heterogeneous. With regard to the discrimination of the menopausal and nonmenopausal groups, the data suggested that, while no clinical conditions other than those attributable to the effects of aging were significantly associated with the menopausal state, medication and surgical procedures for female disorders were significantly related to menopause.
Adult↗
Characterization of heteropolymeric hexosaminidase A in human X mouse hybrid cells.
Expression of heteropolymeric hexosaminidase A activity is reported in a human X mouse hybrid cell line that contains an X/15 translocation chromosome but lacks human chromosome 5 and has no detectable human hexosaminidase B activity. (Hexosaminidase is beta-N-acetylglucosaminidase; EC 3.2.1.30; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase.) That the "hexosaminidase A" enzyme of these cells contains the human hexosaminidase-alpha subunit and not the human hexosaminidase-beta subunit is indicated by the cells' reactions to specific antisera prepared against the alpha subunit and against the beta subunit. Our results indicate that the "hexosaminidase A" activity in this hybrid cell line is the expression of a hybrid molecule composed of human hexosaminidase-alpha subunit and a mouse hexosaminidase subunit. These results are consistent with the hypothesis that the human hexosaminidase A enzyme is formed from alpha and beta subunits coded for by genes on chromosomes 15 and 5, respectively.
Animals↗
Control of expression of differentiated functions in neuroblastoma cell hybrids.
Cell hybrids have been extensively utilized for gene mapping; more than 50 enzymes and nonenzyme proteins have been assigned to individual human chromosomes. Hybrids have also been used in the study of differentiation; fusions involving mouse or human neuroblastoma cells and various nonneuronal lines resulted in hybrid cells that continued to express neuronspecific functions. The expression of the differentiated state is, however, not an all-or-none phenomenon: One neuronal trait may be evident in such hybrids, in the absence of others. The potential usefulness of the human neuroblastoma hybrids for the assignment of genes involved in the expression of differentiated functions to specific chromosomes is discussed.
Animals↗
Tay-Sachs' and Sandhoff's diseases: the assignment of genes for hexosaminidase A and B to individual human chromosomes.
The techniques of somatic cell genetics have been used to establish the linkage relationships of loci coding for two forms (A and B) of hexosaminidase (EC 3.2.1.30; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase) and to determine whether a structural relationship exists between these forms. In a series of human-mouse hybrid cell lines, hexosaminidase A and B segregated independently. Our results and those reported by other investigators are used to analyze the proposed structural models for hexosaminidase. We have also been able to establish a syntenic relationship between the gene locus responsible for the expression of hexosaminidase A and those responsible for mannosephosphate isomerase and pyruvate kinase-3 and to assign the gene for hexosaminidase B to chromosome 5 in man. There is thus a linkage between specific human autosomes and enzymes implicated in the production of lipid storage diseases.
Animals↗
Racial variation in diabetes mellitus in Japanese and Caucasians living in Hawaii.
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Adult↗
Proceedings: Hexosaminidase B: assignment of a locus involved in its expression to chromosome 5 in man.
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Animals↗