Biomedical subjects
M Park
Publications and source records attributed to M Park.
Papillary cystic neoplasm of the pancreas.
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Lonesome receptors find their mates.
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Spontaneous rupture of a normal bladder.
We have reported a case of spontaneous rupture of a normal urinary bladder. Patients with this rare condition characteristically have a recent history of heavy alcohol intake, sudden onset of abdominal pain coincidental with bloody urine, generalized peritonitis, and abnormal renal chemistry. A high index of suspicion will lead to early diagnosis and treatment, minimizing the mortality attributed to this condition.
Alternative splicing generates isoforms of the met receptor tyrosine kinase which undergo differential processing.
The met proto-oncogene is a member of the family of tyrosine kinase growth factor receptors. We describe the isolation and characterization of a cDNA clone (pOK) for the met receptor from a gastric carcinoma cell line. This clone differs from the published cDNA clone by the absence of 54 bp predicted to encode 18 amino acids in the extracellular domain. The pOK cDNA corresponds to the most abundant met RNA species of 8 kb expressed in human cell lines and tissue, and we show that there are in fact two 8-kb met receptor tyrosine kinase (RTK) isoforms that are generated by alternative splicing. This newly described met isoform when transiently expressed in COS cells encodes a protein of 190 kDa which corresponds in size to the p190 met alpha beta heterodimer expressed in human cell lines. Furthermore, we show that the 190-kDa product of pOK consists of the 140-kDa met beta subunit associated with the 50-kDa met alpha subunit. This finding suggests that both the alpha and beta met chains are encoded by this construct and confirms the hypothesis that a single chain precursor is cleaved to produce both subunits of met. In contrast, the previously characterized met isoform corresponds to a minor met RNA species and encodes a protein of 170 kDa that is not cleaved yet is processed in a manner that allows cell surface expression. Both met RTK isoforms are autophosphorylated in the in vitro kinase assay. These results suggest that different isoforms of the met RTK may have distinct biological activities.
Efficacy and distribution of single-dose preoperative antibiotic prophylaxis in high-risk gastroduodenal surgery.
Although a single preoperative dose of antibiotic is now the accepted means of preventing postoperative surgical infection, the method has not been investigated adequately. In patients at high risk of infection who underwent gastroduodenal operations, the authors compared single-dose prophylaxis by intravenous cefotaxime (26 patients) with short-course perioperative prophylaxis (27 patients). No wound infection occurred, but in one patient in each group a subphrenic abscess developed after leakage at the anastomosis. The half-life of cefotaxime (1.23 +/- 0.12 hours) and its apparent volume of distribution (16.7 +/- 2.6 L/1.73 m2 resulted in perioperative levels of the antibiotic in blood (34.76 +/- 4.21 micrograms/mL), gastric mucosa (32.04 +/- 5.22 micrograms/mL) and subcutaneous fat (24.98 +/- 5.89 micrograms/mL) more than twice the usual minimal inhibitory concentration of the drug for organisms grown from the stomach contents and wound fat. These clinical and pharmacologic findings validate the efficacy of a single preoperative intravenous dose of the antibiotic in preventing postoperative infection in high-risk patients who undergo gastroduodenal surgery.
Simple elective cholecystectomy: to drain or not.
We performed a large single-center prospective randomized controlled study to assess the role of peritoneal drainage in simple elective cholecystectomy. In 248 patients, drains were omitted; 122 patients had closed suction drains and 124 had Penrose drains. There were no deaths, and no patient required reoperation or drainage of a subhepatic collection. Wound infections occurred in eight patients with drains and in six patients without. Most infections were staphylococcal. Postoperative pulmonary complications and hospital stays were similar in patients with and without drains. Statistical analysis of the 10 available prospective controlled randomized studies (1,920 patients) by the method of odds ratios supported our findings. Simple elective cholecystectomy is safe without peritoneal drainage, but short-term drains do not increase morbidity.
Blood product monitoring using statistical aggregate data analysis.
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Structure, tissue-specific expression, and transforming activity of the mouse met protooncogene.
A 6.7-kilobase met complementary DNA (cDNA) was isolated from a pcD cDNA library prepared from C3H mouse fibroblast cell line polyadenylated RNA. Sequence analysis of 6.7-kilobase met cDNA insert revealed that it contained the entire open reading frame and shared an overall homology of 88.1% with the human met gene. Using the mouse met cDNA as probe, high levels of met expression were observed in the kidney, brain, lung, skin, and embryonic tissue as well as in several factor responsive mouse myeloid cell lines. Under SV40 promoter control, the mouse met protooncogene cDNA in the pCD vector was able to transform NIH 3T3 cells. These transformed cells possess multiple copies of mouse met cDNA and exhibit properties of malignant cells, including growth in soft agar and induction of tumors in nude mice. Tumor explant cell lines analyzed by Western blot also reveal the presence of high levels of Mr 170,000 and 140,000 met protein product(s).
Analysis by pulsed field gel electrophoresis reveals complex rearrangements in two MET alleles in a chemically-treated human cell line, MNNG-HOS.
We have previously shown that two alleles of the MET locus are independently rearranged in the chemically-treated human cell line MNNG-HOS. One allele is the TPR-MET oncogene which was activated by fusion of the MET locus on chromosome 7 with the TPR locus on chromosome 1. The second allele is found on a der(7)t(1;7)(q23;q32) chromosome and is characterized by a deletion of the amino-terminus of the MET extracellular ligand binding domain. Here we present a pulsed field gel electrophoresis analysis which reveals that the two MET allele rearrangements in MNNG-HOS cells are more complex than originally thought. The breakpoint in MET on der(7) has been molecularly cloned and, unexpectedly, we found that rearrangement in this allele involves sequences derived from chromosome 2. Moreover, the rearrangement producing der(7) involves an inversion of the MET locus or a more complex alteration. Analysis of hybrid cells containing TPR-MET demonstrated that both the upstream and downstream portions of MET are conserved in this rearrangement and that oncogene activation occurred by an insertion of TPR sequences into the MET locus. These findings illustrate that when examined at the molecular level some chromosome abnormalities can be extremely complex and, thus, are of limited value in gene mapping studies.
Epstein-Barr virus DNA sequences in precursor monocyte-macrophage cell lines established from the bone marrow of children with maturation defects of haematopoiesis.
Epstein-Barr virus (EBV) DNA sequences were detected in four established monoblast or early monocytic cell lines (CM-S, ROV-S, CV-S and AD-S) obtained from bone marrow of children suffering from maturation defects of haematopoiesis. EBV is present in these cells in a latent state. The viral DNA in these cell lines was analysed by Southern blot hybridization, using a set of cloned EBV DNA fragments from the EBV strain B95-8 as probes. A common spectrum of highly related but distinguishable EBV DNA restriction enzyme sequences was found, suggesting some genomic diversity. Propagation of the cells in long-term culture revealed a gradual decrease of EBV copies per cell in all lines with some minor changes in the restriction pattern of the EBV DNA. These findings demonstrate that human precursor monocyte cells may be susceptible to infection by EBV.
[Changes in cerebellar iron metabolism and their prevention by allopurinol in oxidative stress related to acute ethanol administration in rats].
An acute ethanol load results in an increased total nonheme iron and cytosolic low molecular weight iron content in rat cerebellum. At the same time the cerebellar susceptibility to lipid peroxidation is enhanced whereas the alpha-tocopherol and ascorbate content is decreased. These changes argue for a cerebellar ethanol-induced oxidative stress, which is prevented by prior allopurinol administration.
Is neomycin necessary for bowel preparation in surgery of the colon? Oral neomycin plus erythromycin versus erythromycin-metronidazole.
In 132 patients who underwent elective surgery of the colon, the value of bowel preparation with a conventional oral antibiotic preparation of neomycin-erythromycin (N-E) was compared with erythromycin-metronidazole (E-M). Of 125 patients who were available for assessment, 61 received N-E and 64 E-M. The two groups were evenly matched. Two wound infections occurred in patients receiving E-M, neither due to anaerobic bacteria, but seven wound infections developed in patients given N-E (p = 0.057), five of them caused by anaerobic bacteria. Anaerobic bacteria of the colon are the dominant cause of postoperative wound infection in elective surgery of the colon. Adequate antibiotic preparation directed against these bacteria makes the use of neomycin unnecessary.
Ocular manifestations of Lyme disease.
The incidence of Lyme disease has been increasing at alarming rates in recent years. Being the most commonly reported tickborne bacterial disease in the United States, it now outnumbers Rocky Mountain spotted fever by a ratio of almost 2:1. It is a multisystem illness and can manifest itself with dermatologic, neurologic, cardiac and rheumatologic involvement. The ocular complications of Lyme disease can present as one of the more ominous signs during the course of the illness. The detection of the disease and proper referral by the optometrist may permit more appropriate treatment, and thus, a better prognosis of the illness.
Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases.
The proteins encoded by the human TPR-MET oncogene (p 65tpr-met) and the human MET protooncogene (p140met) have been identified. The p65tpr-met and p140met, as well as a truncated TPR-MET product expressed in Escherichia coli, p50met, are autophosphorylated in vitro on tyrosine residues. Using the immunocomplex kinase assay, p140met activity was detected in various human tumor epithelial cell lines. In vivo, p65tpr-met is phosphorylated on both serine and tyrosine residues, while p140met is phosphorylated on serine and threonine. p140met is labeled by cell-surface iodination procedures, suggesting that it is a receptor-like transmembrane protein-tyrosine kinase.
Two rearranged MET alleles in MNNG-HOS cells reveal the orientation of MET on chromosome 7 to other markers tightly linked to the cystic fibrosis locus.
We have found that two alleles of the MET locus are rearranged in the human cell line MNNG-HOS. One allele is the previously characterized TPR-MET oncogene and the other is found on a der(7)t(1;7)(q23;q32) marker chromosome. These data and in situ chromosomal hybridization analysis would indicate that MET and, therefore, the cystic fibrosis locus are located at bands q31-q32 on human chromosome 7. Using somatic cell hybrids, we show that the chromosome containing the TPR-MET oncogene is grossly rearranged and contains both the upstream and downstream portions of the MET protooncogene locus. These results demonstrate that the TPR-MET oncogene rearrangement involving chromosomes 1 and 7 is either due to an insertion of TPR sequences into the MET locus or is more complex. We also show that the upstream MET protooncogene locus is deleted on der(7), while the downstream portion is retained. We cannot exclude that this is due to an interstitial chromosomal deletion or to a more complex rearrangement, but if MET maps at the breakpoint in der(7), then the 3' end of the MET transcription unit should be oriented towards the centromere. We also show that other DNA restriction fragment length polymorphism markers tightly linked with the inheritance of cystic fibrosis are deleted on der(7).
Distribution of 10-formyltetrahydrofolate synthetase in eubacteria.
The distribution of 10-formyltetrahydrofolate synthetase, which activates formate for use as a one-carbon donor in a variety of biosynthetic reactions, was determined for a variety of eubacteria. Organisms from several genera were found to lack detectable synthetase activity; however, all organisms tested were found to contain 5,10-methylenetetrahydrofolate dehydrogenase activity.
Regulation of cholesterol metabolism in fetal rabbit aorta: role of amniotic fluid factors.
This study shows that amniotic fluid enhances cholesterol esterification in arterial wall, as measured by in vitro assay of acyl-CoA:cholesterol acyltransferase (ACAT) activity and by incorporation of oleic acid to cholesteryl esters in cultured fetal aortas and smooth muscle cells. This property is mostly evident in the fraction of molecular weight greater than 100,000, and it is abolished by delipidation, indicating that stimulating factor is probably lipoprotein in nature. Despite an increased cholesterol esterification by the presence of amniotic fluid in medium of cultured fetal aortas, the content of cholesterol and cholesteryl esters was much lower. The cellular structures are better preserved in explants cultured with amniotic fluid than in control animals. This study indicates that amniotic fluid contains factors that may have a pronounced effect on arterial wall during development.