Biomedical subjects

T C King

Publications and source records attributed to T C King.

At least 19 recordsLinked to original sources

PubMed1996

Synchronous colon carcinomas: molecular-genetic evidence for multicentricity.

BACKGROUND: The synchronous presentation of multiple colonic adenocarcinomas is an unusual, but well-recognized event accounting for approximately 2-11% of these neoplasms. Synchronous tumors may have a different biology and prognosis than solitary tumors. Evidence based on measurement of DNA ploidy suggests that a significant percentage of synchronous tumors have a common clonal origin, probably resulting from translumenal metastasis. METHODS: Fifteen synchronous colorectal cancers (30 tumors) were examined for histologic differences as well as genetic mutations. p53 gene abnormalities were detected by polymerase chain reaction (PCR) followed by single-strand conformation polymorphism analysis. Ki-ras mutations were detected by PCR followed by oligonucleotide-specific hybridization. RESULTS: p53 gene mutations were detected in 12 of 30 tumors. In only one case was the same p53 mutation present in both tumors from one patient. Similarly, Ki-ras mutations were observed in 9 of 30 tumors. Concordant Ki-ras mutations were observed in only one case, which was also concordant for p53 mutation. CONCLUSION: Because p53 and Ki-ras mutations tend to occur fairly early in tumor development, it seems likely that cases discordant for p53 and Ki-ras mutations represent independently developing tumor foci. Taken together, these findings strongly suggest that the great majority of synchronous colonic adenocarcinomas arise as independent neoplasms and their worsened prognosis is not a result of unusually early metastatic spread.

Adenocarcinoma↗

PubMed1996

Extramedullary myeloid cell tumors arising in the setting of chronic myelomonocytic leukemia. A report of two cases.

We report two cases of extramedullary myeloid cell tumor that arose in patients with chronic myelomonocytic leukemia. In both cases, the tumors were difficult to recognize histologically because the neoplasms lacked cytological evidence of granulocyte maturation, such as cytoplasmic granulation or eosinophilic myelocytes, and the Leder stains for chloroacetate esterase were negative. Immunohistochemical studies were necessary to establish the correct diagnosis. The neoplastic cells in both tumors expressed myeloperoxidase, lysozyme, and CD43 and were negative for B-cell, T-cell, and other nonhematopoietic antigens tested. We report these cases to emphasize that extramedullary myeloid cell tumors may rarely precede transformation to acute myeloid leukemia in patients with chronic myelomonocytic leukemia. Extramedullary myeloid cell tumors of monocytic lineage may be difficult to recognize in routine and Leder-stained sections, and immunohistochemical studies may be essential for establishing the diagnosis.

Aged↗

PubMed1996

Monoclonal B-cell population mimicking lymphoma in a patient with multiple sclerosis.

BACKGROUND: Diagnosis of intraparenchymal brain lesions has usually required invasive diagnostic procedures, because too few cells are shed into cerebrospinal fluid to permit cytologic diagnosis. Polymerase chain reaction technology makes it possible to identify cell populations that are present at a much lower frequency than traditional techniques. CASE REPORT: A young woman presented with multiple brain lesions raised the question of primary central nervous system lymphoma. Polymerase chain reaction analysis of cerebrospinal fluid showed evidence of a monoclonal B-cell population heightening suspicion of lymphoma. Brain biopsy showed acute demyelination most consistent with multiple sclerosis. CONCLUSION: Although T-cell restriction has been demonstrated in multiple sclerosis lesions, the finding of a monoclonal B-cell population was unexpected and to our knowledge has not been previously reported. This case emphasizes that monoclonality is not always indicative of a neoplastic process, particularly in the central nervous system.

Adult↗

PubMed1995

Retrospective diagnosis of sickle cell-hemoglobin C disease and parvovirus infection by molecular DNA analysis of postmortem tissue.

A previously healthy 30-year-old African-American woman presented with a history of sickle cell trait and a nonspecific prodromal illness with severe bone pain. She experienced rapid clinical deterioration with seizures and cardiorespiratory arrest leading to death. Autopsy showed necrotic bone marrow with extensive bone marrow emboli. Parvovirus infection was documented by polymerase chain reaction (PCR) although diagnostic intranuclear inclusions or giant pronormoblasts were not present. The diagnosis of sickle cell-hemoglobin C disease (hemoglobin SC disease) was also established postmortem by DNA sequencing of PCR products. This case illustrates the use and versatility of PCR for analysis of formalin-fixed paraffin-embedded autopsy tissue.

Adult↗

PubMed1995

Lymphoma of the mucosa-associated lymphoid tissue of the lung. A multifocal case of common clonal origin.

Low-grade B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) are extranodal tumors that tend to be localized. In this case report, the authors describe an unusual multifocal pulmonary MALT lymphoma, which presented radiologically as three discrete lesions involving two separate lobes of the lung, in addition to numerous separate macroscopic and microscopic foci of disease. The lesions were composed of centrocyte-like cells and cytologically bland plasma cells surrounding reactive lymphoid follicles with focal areas resembling lymphoid interstitial pneumonia (LIP). Immunohistochemical studies demonstrated a predominance of immunoglobulin kappa light chain positive plasma cells in the largest lesion. A polymerase chain reaction (PCR) assay demonstrated conserved immunoglobulin heavy chain gene rearrangements in the large tumor nodules as well as microscopic foci resembling LIP. This case illustrates the utility of PCR for identifying the clonal nature of lymphoid lesions that are too small or heterogeneous to unequivocally assess by other means.

Base Sequence↗

PubMed1995

Isolated metastasis to a pulmonary hamartoma.

Intrapulmonary hamartomas are the most common benign pulmonary neoplasm, and malignant degeneration is exceedingly rare. Only a minority produce symptoms, and their major clinical significance is their ability to simulate a malignant pulmonary neoplasm in radiologic studies. Here we report a case of apparently localized prostatic adenocarcinoma with isolated metastasis to an intrapulmonary hamartoma. The pulmonary lesion was identified during staging and was ultimately resected. Prostatic adenocarcinoma involved the hamartoma extensively but did not involve adjacent lung tissue. The hamartoma was otherwise typical with predominantly cartilaginous differentiation. The malignant glands within the hamartoma showed strong reactivity for prostate specific antigen, excluding the possibility of malignant change within the hamartoma. To our knowledge, metastasis to a pulmonary hamartoma has not been previously reported, and this case raises several issues. The pattern of tumor spread suggests an affinity of the tumor cells for the hamartoma. The known propensity of prostatic adenocarcinoma to metastasize to osseous sites might underlie its apparent tropism for the cartilaginous milieu of a pulmonary hamartoma. Accurate pathologic staging of this patient's prostatic adenocarcinoma prevented a needless radical prostatectomy, and complete cancer staging may require histologic examination of clinically typical pulmonary hamartomas.

Adenocarcinoma↗

PubMed1992

Occult diaphragm injuries at celiotomy for left chest stab wounds.

No dependable test exists for diagnosis of diaphragmatic injury in asymptomatic patients with thoraco-abdominal stab wounds. Forty-one consecutive patients with anterior stab wounds of the lower left chest were treated in a 30-month period. In the 21 patients seen during the first 15 months, operations were reserved for those with peritoneal signs or continuing blood loss. Ten of these 21 patients (48%) required celiotomy; 2 patients (10%) had isolated diaphragm injuries and there was one negative celiotomy. Of the eleven patients who were not explored, 2 (18%) returned within 18 months after injury with an incarcerated diaphragmatic hernia. During the subsequent 15 months, the next 20 patients were managed by routine celiotomy in a prospective study. The admission systolic blood pressure and incidence of pneumothorax, celiotomy, diaphragm injury, isolated diaphragm injury, and unnecessary celiotomy in these two groups were compared. Ten patients in the prospective group (50%) were found to have isolated diaphragm injuries (P less than 0.005) and 7 (35%) had negative celiotomies (P less than 0.02). The true incidence of occult diaphragm injuries may be underestimated. In the prospectively studied group, the policy of routine celiotomy for anterior stab wounds of the lower left chest resulted in recognition and repair of a fivefold greater number of isolated diaphragm injuries. In the absence of a reliable, noninvasive test to diagnose penetration of the diaphragm, celiotomy should be considered in light of the risks of late strangulation.

Adolescent↗

PubMed1991

Therapeutic management of ocular squamous cell carcinoma in the horse: 43 cases (1979-1989).

The records of 50 horses with ocular squamous cell carcinoma (OSCC) presented to the University of Florida Veterinary Medical Teaching Hospital over an 11 year period were reviewed to determine the influence of therapy on the outcome of the case. Follow-up information was obtained for 43 of the 50 cases. The disease was more prevalent in the light horse breeds; however, the draft breeds also were at risk. There was no sex predisposition and the average age was 11.8 years. Tumour recurrence was significant when surgery alone was performed. The eyelid and nictitating membrane were the primary sites for tumor recurrence. Cases in which adjunctive therapy was used correlated with a lower rate of recurrence.

Age Factors↗

PubMed1991

Evaluation of a topically administered carbonic anhydrase inhibitor (MK-927) in normotensive and glaucomatous beagles.

A new topically administered anhydrase inhibitor, MK-927, was evaluated for its ocular hypotensive activity in normotensive and glaucomatous Beagles. Single- and multiple-dose studies were performed. Six concentrations of the drug were evaluated in the single-dose study and the 2% solution was used for multiple-dose evaluation. The decrease in intraocular pressure (IOP) was greater in glaucomatous Beagles at the higher concentrations of the drug. The 2 and 4% solutions of MK-927 significantly lowered IOP (mean, 5 mm of Hg; SEM +/- 1.6 and SEM +/- 1.2, respectively) in normotensive and glaucomatous Beagles. In the multiple-dose study, IOP was significantly decreased in the normotensive (mean, 4 mm of Hg; SEM +/- 0.74) and glaucomatous Beagles (mean, 9 mm of Hg; SEM +/- 1.2). The maximal effect was observed by day 4. A contralateral effect was found in glaucomatous Beagles, with the maximal effect on day 4.

Administration, Topical↗

PubMed1990

Hydroxyethyl starch macromolecules reduce myocardial reperfusion injury.

We assessed the value of a fraction of hydroxyethyl starch (HES Pz) in reducing the myocardial reperfusion injury in a canine open-chest model in which 1 hour of left anterior descending coronary artery occlusion was followed by 24 hours of reperfusion. Three treatment infusions (5% of blood volume) were compared: Ringer's lactate, serum albumin, and HES Pz (70% of the macromolecules between 100,000 and 1,000,000 d). When compared with Ringer's lactate and albumin, HES Pz significantly reduced the ratio of 24-hour infarct size to pretreatment area at risk (3% vs 19% and 16%, respectively) and myocardial water content (0.5% vs 3% and 1%). Potassium content differences between injured and normal myocardium were significantly less in the infarct regions of animals receiving HES Pz. In the canine model, HES Pz reduced 1-hour myocardial ischemia reperfusion injury significantly.

Animals↗

PubMed1990

Integration of quality assurance activities into a computerized patient data management system in an intensive care unit.

A prototype computer-based patient data management system (PDMS) was developed for a surgery-anesthesiology intensive care unit (ICU) to reduce the time and staff needed to implement quality assurance (QA) functions. Goals of the system were to make QA functions routine and minimally intrusive to the daily operation of the ICU. PDMS collects general data (eg, admissions and discharges, lengths of stay, and bed utilization rates) and specialized data (eg, specific indicators) unique to the ICU and performs prospective monitoring for the occurrence of specific events (occurrence screening) and retrospective examinations of patient records (targeted reviews). Preliminary results suggest that PDMS facilitates the acquisition and analysis of QA data and reduces the time needed to acquire these data. Research to validate these claims and efforts to improve and expand the prototype system with a permanent production system are in progress.

Analgesics↗

PubMed1989

Structure of the NGFI-A gene and detection of upstream sequences responsible for its transcriptional induction by nerve growth factor.

The NGFI-A gene encodes a "zinc-finger" protein that is rapidly induced by nerve growth factor (NGF) in PC12 rat pheochromocytoma cells. The complete exon/intron organization and nucleotide sequence of the rat NGFI-A gene have been determined. The gene spans 3789 nucleotides (nt) and is interrupted by a single intron at nt 588. All three zinc-finger DNA-binding domains are contiguously coded for within the 3' exon; this is in contrast to the structure described by others for the Xenopus laevis transcription factor TFIIIA gene. To analyze the transcription of this gene, we have determined the transcription start site and nucleotide sequence of the 5' flanking region. Transfection of PC12 cells with a fragment from the 5' flanking region linked to the chloramphenicol acetyltransferase (CAT) gene revealed that it contains an element which imparts an NGF-inducible phenotype to the normally silent CAT gene. Several regions with homologies to recognizable sequence elements are present in this fragment, including a TATA box at nt -27, serum response elements at nt -84, -106, -370, and -408, a cAMP-responsive element at nt -140, and a transcription factor Sp1-binding site at nt -286. These results establish the genomic structure of this mammalian multifinger protein and demonstrate that an NGF-responsive element lies upstream of the NGFI-A gene.

Adrenal Gland Neoplasms↗

PubMed1989

A biophysical approach to capillary permeability.

In this preliminary report, the capillary leakage that occurs after scald injury is considered a biophysical phenomenon and is treated by sealing the "pores," or endothelial gaps, in the capillary membranes with biodegradable macromolecules of the appropriate size and shape. We have measured albumin leakage from standardized scald burns in the rat jejunum with and without variously sized fractions of intravenous macromolecules of hydroxyethyl starch (HES) used as a sealing agent. The observed reduction of albumin leakage from injured capillaries was attributed to the sealing effect. The fraction HES (Fm) with molecular weights of 100,000 to 300,000 daltons performed significantly better (p less than 0.05) as a sealing agent when compared with HES (F1) fraction molecular weights of 300,000 to 3.4 million daltons, HES (Fs) molecular weight less than 50,000 daltons, and two control groups receiving the intravenous Ringer's lactate solution or serum albumin 5%. This capillary sealing phenomenon was shown to be independent of colloid osmotic pressure effect. It is believed to be related to the size and the shape of the noncharged macromolecules.

Animals↗

PubMed1988

Papillary cystadenoma of the mesosalpinx in von Hippel-Lindau disease.

Papillary cystadenoma of the epididymis is an occasional finding in men with von Hippel-Lindau disease. To date, an analogous lesion has not been described in women with the syndrome. We report a case of an asymptomatic papillary cystadenoma of the mesosalpinx found incidentally during surgery for a renal cell carcinoma in a woman with von Hippel-Lindau disease. This finding supports the notion that similar lesions may arise in both men and women with von Hippel-Lindau disease, perhaps from embryologically related portions of the urogenital tract.

Adnexal Diseases↗

PubMed1987

The bovine mitochondrial endonuclease prefers a conserved sequence in the displacement loop region of mitochondrial DNA.

The purified endonuclease of bovine heart mitochondria shows a remarkable preference for a specific site in bovine mtDNA. This site was identified using a recombinant DNA template which includes a 4.9-kilobase portion of the 16-kilobase bovine mitochondrial sequence encompassing all of the displacement loop region. The endonucleolytic target corresponds to an evolutionarily conserved sequence tract of 12 consecutive guanine residues that is found in an otherwise highly divergent domain of the mitochondrial displacement loop region. The preference for this site is several hundred-fold greater than other less favored sites. Unlike other less prominent cleavage loci, the conserved sequence tract is readily nicked in either or both DNA strands, even at 0 degrees C. These findings suggest that there is a specific interaction of the endonuclease with this site in vivo that may be important for mtDNA replication.

Animals↗

PubMed1987

Mapping of control elements in the displacement loop region of bovine mitochondrial DNA.

The genomes of mammalian mitochondria are duplex DNA circles. The two major transcriptional promoters and the origin of DNA replication for one DNA strand are located in a single region which contains no structural genes and occupies about 6% of the genome. This region is called the displacement loop (D-loop) region since it is often found as a novel triplex structure in which the heavy strand of the genome has been partially replicated. This nascent single-stranded DNA segment remains hybridized to the light strand, displacing the heavy strand of the genome over much of the D-loop region. The promoters and the sites of initiation of D-loop DNA synthesis have been mapped in the human and mouse genomes and may show limited sequence conservation. We have mapped these sites in the bovine mitochondrial genome. Some features are conserved between all three species; however, the promoters and the sites of initiation of D-loop DNA synthesis show no primary sequence homology among all species. This lack of sequence homology is in contrast to the greater than 80% sequence conservation which has been reported in portions of the D-loop region which are located distal to the origin of DNA replication and far from the transcriptional promoters. These results imply that closely related species may have developed different means of controlling mitochondrial gene expression.

Animals↗

PubMed1987

Mitochondrial DNA displacement loop structure depends on growth state in bovine cells.

One portion of the mitochondrial genome of mammals contains no structural genes. This so-called displacement loop (D-loop) region includes the two major transcriptional promoters and one of the origins of DNA replication. The D-loop region is often found in a novel triplex structure in which a discrete single-stranded DNA segment is hybridized to one strand of the genome displacing the other strand. The significance of this triplex structure and the possible function of the single-stranded D-loop segment have remained obscure. Here we show that the locations of the major 5' termini of D-loops in growing and nongrowing bovine cells differ by 46 nucleotides. The location of bovine D-loop 5' termini is dependent on the cell cycle but is not directly linked to nuclear DNA replication. The nature of D-loop 5' termini in growing cells is altered by inhibitors of cytoplasmic protein synthesis but not by inhibitors of mitochondrial protein synthesis. Changes in D-loop 5' termini correlate with alterations in transcripts from one of the transcriptional promoters. These findings implicate D-loops in the control of bovine mitochondrial gene expression and suggest mechanisms by which this control might by accomplished.

Animals↗

PubMed1987

Purification and characterization of the potent endonuclease in extracts of bovine heart mitochondria.

A potent endonuclease identified in a crude fraction of soluble proteins from bovine heart mitochondria has been purified 2500-fold and partially characterized. Physical studies of the enzyme indicate a Stokes radius of 30.3 A and a sedimentation coefficient, S20 degrees, w, of 4.1 yielding a native molecule weight of 59,000 and a frictional coefficient of 1.2. Analysis of extensively purified fractions by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals a major band at 29,000 Da accounting for 50% of the total protein and suggesting a dimeric subunit structure. The endonuclease maintains two distinct pH optima: pH 5.1-5.5 and 7-8. Both acid and neutral activities nick supercoiled M13 circular double-stranded replicative form I DNA and fragment single-stranded DNA templates to generate 5'-phosphoryl-3'-hydroxyl breaks. The endonuclease requires a divalent cation (preferring Mn2+ over Mg2+) and is sensitive to N-ethylmaleimide and moderate levels of salt. Analysis of the digestion products of double-stranded DNA after prolonged nuclease treatment yields a mixture of oligonucleotides, 13% of which are di- and trinucleotides. Despite the enzyme's ability to degrade DNA to oligonucleotides under some conditions, a strikingly nonrandom pattern of cleavage is observed when a restriction fragment composed of bovine D-loop DNA is used as a template. In this case, a strong preference for guanine tracts is seen.

Animals↗