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Biomedical subjects

K Stam

Publications and source records attributed to K Stam.

17 recordsLinked to original sources
PubMed2001

An observational study of pre-operative transcranial Doppler examinations to predict cerebral hyperperfusion following carotid endarterectomies.

The objective of this observational study was to determine whether pre-operative transcranial Doppler measurements could identify patients at risk for early cerebral hyperperfusion following carotid endarterectomies. Fifty-five patients (mean age 64.4 years) with symptomatic internal carotid artery stenosis were included. Pre-operative transcranial Doppler measurements included middle cerebral artery blood flow velocities at normocapnia, pulsatility indices and estimation of the cerebro-vascular reserve capacity ipsilateral to the internal carotid artery stenosis. The percentage change in blood flow velocities before and at the end of the procedure was calculated. Early cerebral hyperperfusion was defined as an increase of mean blood flow velocity of more than 100% at the end of the carotid endarterectomy. Early cerebral hyperperfusion was observed in 9.2%. Cerebral hyperperfusion was seen in patients with a subtotal carotid artery stenosis in combination with reduced pre-operative blood flow velocity and pulsatility. The post-operative stroke incidence in patients with an early cerebral hyperperfusion was tenfold higher compared to patients who did not experience early hyperperfusion. A prospective clinical trial is warranted to determine whether transcranial Doppler parameters can be used to indicate patients at risk for reperfusion strokes following carotid endarterectomies.

Adult↗
PubMed1997

Contexts and patterns of men's commercial sexual partnerships in northeastern Thailand: implications for AIDS prevention.

Results of an exploratory research project elaborating the contexts, patterns and specific scenarios of the commercial sexual activity of northeastern Thai men are reported. Data were collected using face-to-face surveys, focus groups, key informant interviews and observations in 32 northeastern villages (n = 744 men), 18 migrant labour camps housing sugarcane workers (n = 219 men), and five cattlemarkets in northeast Thailand. Fifty percent of married men and 43% of single men had visited female sex workers (FSW). Female sex worker visits occurred primarily prior to marriage, though 13% of married men had purchased sexual services within the past year. Nonmarital sexual activity was set within the socio-cultural frameworks of poverty, circular migration, a large commercial sex sector, and a belief system about men's sexuality and men's and women's gender roles. Sexual services were typically purchased as part of friendship group partying (paiy tiaow) and generally included heavy alcohol consumption. The most common scenario for visiting FSWs involved brothels, though cattlemarkets, festivals, and migrant labour situations were also scenarios for FSW contact. These each had unique characteristics that affected the likelihood that condoms would be used. The further the specifics of a scenario (as evaluated by men) diverged from those of brothel contact with an FSW, the less likely men were to identify this as having the potential for HIV transmission and the less likely they were to use a condom. AIDS prevention campaigns must be developed that are sensitive to the socio-cultural framework, contexts and specific scenarios within which nonmarital sexual contacts occur.

Adolescent↗
PubMed1996

Single chain Ig/gamma gene-redirected human T lymphocytes produce cytokines, specifically lyse tumor cells, and recycle lytic capacity.

To enable construction of CTL with known predefined Ab specificity for adoptive immunotherapy, we constructed a chimeric scFv/gamma gene composed of the variable regions of a mAb joined to the Fc(epsilon)RI signaling receptor gamma-chain of mast cells. Introduction of this chimeric receptor into CTL rendered these lymphocytes specific for renal cell carcinoma. This approach combines the specificity of tumor-selective Abs with the efficacy of CTL to destroy tumor cells. We not only demonstrated that the transduced CTL functionally express the scFv/gamma receptor for a prolonged period of time (4.5 mo of in vitro culture), but also showed high levels of Ab-dictated lysis of renal cell carcinoma similar to that of normal CTL, and importantly, we demonstrated that these CTL can recycle their lytic activity. Moreover, these scFv/gamma-expressing T lymphocytes produce cytokines upon stimulation with the relevant target cell. These results together with the donor independence of our gene transduction protocol demonstrate the feasibility of redirecting T lymphocytes for cancer treatment.

Base Sequence↗
PubMed1996

Umbilical cord transforming growth factor-beta 3: isolation, comparison with recombinant TGF-beta 3 and cellular localization.

The transforming growth factor beta (TGF-beta) family of growth modulators play critical roles in tissue development and maintenance. Recent data suggest that individual TGF-beta isoforms (TGF-beta 1, -beta 2 and -beta 3) have overlapping yet distinct biological actions and target cell specificities, both in developing and adult tissues. The TGF-beta 3 isoform was purified to homogeneity from both natural and recombinant sources and characterized by laser desorption mass spectrometry, by protein sequencing, by amino acid analysis and by biological activity. TGF-beta 3 was the major TGF-beta isoform in umbilical cord (230 ng/g), and was physically and biologically indistinguishable from recombinant TGF-beta 3 and from the tumor growth inhibitory (TGI) protein found in umbilical cord. Immunohistochemistry using antipeptide TGF-beta 3 specific antibody showed TGF-beta 3 localization in perivascular smooth muscle.

Amino Acid Sequence↗
PubMed1995

Physical and biological characterization of a growth-inhibitory activity purified from the neuroepithelioma cell line A673.

Epithelial- and haematopoietic-cell growth-inhibitory activities have been identified in the conditioned medium of the human peripheral neuroepithelioma cell line A673. An A673-cell-derived growth-inhibitory activity was previously fractionated into two distinct components which inhibited the proliferation of human carcinoma and leukaemia cells in culture. One inhibitory activity was shown to comprise interleukin-1 alpha (IL-1 alpha). Here, we have purified to homogeneity a distinct activity which inhibited the growth of the epithelial cells in vitro. Using a combination of protein-sequence analysis and mass spectrometry, we demonstrated that biological activity can be assigned to a dimeric protein with a molecular mass of 25,576 (+/- 4) Da and an N-terminal sequence identical with that of transforming growth factor-beta 1 (TGF-beta 1). Further characterization of the growth inhibitor with TGF-beta-isoform-specific antibodies showed that > 90% of the bioactivity consists of TGF-beta 1 and not TGF-beta 2 or TGF-beta 3. Although A673 cells were growth-inhibited by exogenous TGF-beta 1, we showed that TGF-beta 1 in A673-cell-conditioned media was present in the latent, biologically inactive, form which did not act as an autocrine growth modulator of A673 cells in vitro.

Amino Acid Sequence↗
PubMed1994

Prevention of chemotherapy-induced ulcerative mucositis by transforming growth factor beta 3.

Mucositis is a common, dose-limiting complication in patients receiving cancer chemotherapy, which appears to be a consequence of the rate of epithelial proliferation. The beta transforming growth factors have been shown to be negative regulators of epithelial cell proliferation. Here we show that transforming growth factor beta 3 administration reduced proliferation of oral epithelium in vitro and in vivo. Topical application of transforming growth factor beta 3 to the oral mucosa of the Syrian golden hamster prior to chemotherapy significantly reduced the incidence, severity, and duration of oral mucositis, reduced chemotherapy-associated weight loss, and increased survival.

Animals↗
PubMed1987

Evidence that the phl gene encodes a 160,000-dalton phosphoprotein with associated kinase activity.

In chronic myelocytic leukemia, the human c-abl oncogene is translocated from chromosome 9 to a region on chromosome 22 designated as the breakpoint cluster region (bcr) (A. de Klein, A. Guerts van Kessel, G. Grosveld, C. R. Bartram, A. Hagemeyer, D. Bootsma, N. K. Spurr, N. Heisterkamp, J. Groffen, and J. R. Stephenson, Nature (London) 300:765-767, 1982; J. Groffen, J. R. Stephenson, N. Heisterkamp, A. de Klein, C. R. Bartram, and G. Grosveld, Cell 36:93-99.) Abnormal c-abl homologous mRNA and protein have been detected in the leukemic cells of patients with chronic myelocytic leukemia (E. Canaani, D. Stein-Saltz, E. Aghai, R. P. Gale, A. Berrebi, and E. Januszewicz, Lancet 1:593-595, 1984; S. J. Collins and M. T. Groudine, Proc. Natl. Acad. Sci. USA 80:4813-4817, 1983; R. P. Gale and E. Canaani, Proc. Natl. Acad. Sci. USA 81:5648-5652, 1984; J. B. Konopka, S. M. Watanabe, J. W. Singer, S. J. Collins, and O. N. Witte, Proc. Natl. Acad. Sci. USA 82:1810-1814, 1985). The abnormal mRNA represents a chimeric transcript consisting of 5' bcr and 3' c-abl sequences (G. Grosveld, J. Verwoerd, T. van Agthoven, A. de Klein, K. L. Ramachandran, N. Heisterkamp, K. Stam, and J. Groffen, Mol. Cell. Biol. 6:607-616, 1986; E. Shtivelman, B. Lifshitz, R. B. Gale, and E. Canaani, Nature (London) 315:550-554, 1985; K. Stam, N. Heisterkamp, G. Grosveld, A. de Klein, R. S. Verma, M. Coleman, H. Dosik, and J. Groffen, N. Engl. J. Med. 313:1429-1433, 1985). In the present study, we demonstrated that the abnormal c-abl protein is a fusion protein. In addition, the normal gene encompassing bcr sequences was shown to encode a 160,000-dalton phosphoprotein with an associated serine or threonine kinase activity. We propose that this gene be designated phl, reserving the term bcr for the region within the phl gene encompassing the Ph' translocation breakpoints.

Cell Line↗
PubMed1986

The chronic myelocytic cell line K562 contains a breakpoint in bcr and produces a chimeric bcr/c-abl transcript.

In the DNAs of all Ph1-positive chronic myelocytic leukemia patients studied to date, a breakpoint on chromosome 22 (the Ph1 chromosome) can be demonstrated with a probe from the bcr (breakpoint cluster region). Although the K562 cell line was established from cells of a chronic myelocytic leukemia patient, we have been unable to detect the Ph1 chromosome by cytogenetic means. Employing a probe from the 5' region of bcr, we have cloned an amplified Ph1 breakpoint fragment from K562. This demonstrates that K562 contains multiple remnants of a Ph1 chromosome with a breakpoint within bcr and thus may serve as a model system for the study of Ph1-positive chronic myelocytic leukemia at a molecular level. The isolation of bcr cDNA sequences shows that parts of bcr encode a protein. Employing K562, we demonstrate the presence of an abnormally sized mRNA species hybridizing to c-abl and to a bcr cDNA probe, indicating the possible consequence of the Ph1 translocation on a transcriptional level in chronic myelocytic leukemia. The isolation and sequencing of a cDNA containing the breakpoint area of this mRNA provide further evidence for its chimeric structure. Cloning of large stretches of chromosomal DNA flanking bcr and c-abl sequences in K562 and identification of the exons participating in the formation of the chimeric mRNA shows that a splice of at least 99 kilobases is made to fuse the 3' bcr exon to the 5' c-abl exon. Furthermore two chimeric cDNAs were isolated containing chromosome 9 sequences that map 43.5 kilobases downstream from the K562 breakpoint. These chromosome 9 sequences neither hybridize to the 8.5-kilobase chimeric c-abl mRNA nor to normal c-abl mRNAs in Hela cells and probably represent incorrect splicing products present in the K562 cell line.

Amino Acid Sequence↗
PubMed1985

Evidence of a new chimeric bcr/c-abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome.

The hallmark of chronic myelocytic leukemia is the presence of the Philadelphia chromosome (Ph1). In recent studies, we obtained data that strongly suggested the involvement of an oncogene, c-abl, in this type of leukemia. This oncogene, normally located on chromosome 9, is translocated to chromosome 22 as a result of the Ph1 translocation. In addition, we identified a region on chromosome 22, the breakpoint cluster region (bcr), which contains the chromosomal breakpoint in all patients with chronic myelocytic leukemia who are positive for Ph1. Recent studies have suggested that the bcr is part of a gene that is truncated as a consequence of the Ph1 translocation. The deleted part of this gene could be replaced by c-abl sequences; to test this hypothesis we analyzed the RNA of five patients with chronic myelocytic leukemia. All five had chimeric bcr/c-abl messenger RNA, suggesting that the deleterious effects of this disease can be associated with an abnormal chimeric protein encoded by the bcr and the c-abl oncogene.

Adult↗
PubMedDate not supplied

Structural organization of the bcr gene and its role in the Ph' translocation.

The Philadelphia (Ph') chromosome, an abnormal chromosome 22 (ref. 1), is one of the best-known examples of a specific human chromosomal abnormality strongly associated with one form of human leukaemia, chronic myelocytic leukaemia (CML). The finding that a small region of chromosome 9 which includes the c-abl oncogene is translocated to chromosome 22 prompted studies to elucidate the molecular mechanisms involved in this disease. We have demonstrated previously that the chromosome 9 of one patient with CML contains a breakpoint 14 kilobases (kb) 5' of the most 5' v-abl-homologous exon. These data suggest a role for c-abl in CML, a theory supported by the presence of an abnormally sized abl messenger RNA and protein in the CML cell line K562. The region involved in the translocation on chromosome 22 has also been identified: all Ph'-positive patients examined to date have a breakpoint within a 5.8-kb region, for which we have proposed the name 'breakpoint cluster region' (bcr). To determine whether bcr contains protein-encoding regions, probes from bcr were tested for their ability to hybridize to complementary DNA sequences. A 0.6-kb HindIII/BamHI bcr restriction enzyme fragment proved suitable for isolating several cDNA clones from a human fibroblast cDNA library. Using bcr cDNA sequences, we obtained data strongly suggesting the presence of a chimaeric bcr/abl mRNA in the leukaemic cells of Ph'-positive CML patients. The recent isolation of cDNA clones containing bcr and abl sequences confirms this finding. Because the bcr part of the chimaeric mRNA could be required to induce the transforming activity of the human c-abl oncogene, we have now initiated studies to characterize the normal 'bcr gene' and to determine the effect of a translocation within its coding domain. We demonstrate that as a result of the Ph' translocation, a variable number of bcr exons are included in the chimaeric bcr/abl mRNA. The bcr gene sequences in this mRNA could be responsible for the transition of the abl cellular proto-oncogene into an oncogene.

Base Sequence↗