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Biomedical subjects

D Coit

Publications and source records attributed to D Coit.

At least 19 recordsLinked to original sources
PubMed1994

Prospective evaluation of unilateral adrenal masses in patients with operable non-small-cell lung cancer. Impact of magnetic resonance imaging.

UNLABELLED: We designed a prospective study to evaluate the accuracy of magnetic resonance imaging in distinguishing a benign from a malignant adrenal mass in patients with otherwise operable non-small-cell lung cancer. METHODS: Potentially operable non-small-cell lung cancer was prospectively staged. If a unilateral adrenal mass was found by computed tomographic scanning, respiratory compensated and cardiac gated thin section magnetic resonance imaging of the adrenal glands was done. One radiologist interpreted the magnetic resonance imaging scan blinded and, on the basis of the relative signal strengths of the T1- and T2-weighted images, judged whether the adrenal mass was benign or malignant. The patients then underwent a percutaneous needle biopsy of the adrenal mass, if technically feasible. If the result of the needle biopsy was nondiagnostic or if the biopsy was not feasible, an adrenalectomy through a posterior approach was performed. RESULTS: Twenty-seven patients with a unilateral adrenal mass entered the study-11 men and 16 women whose ages ranged from 42 to 75 years (median 58 years). Four patients had epidermoid and 23 adenocarcinoma of the lung. The clinical locoregional stage was I in 9, II in 1, IIIA in 16, and IIIB in 1. Twenty-five completed the magnetic resonance imaging procedure. Five adrenal masses (19%) were metastatic non-small-cell lung cancer (adenocarcinoma = 4, epidermoid = 1); 22 masses (81%) were benign (adenoma = 20, hyperplasia = 2). There were no significant differences in age, sex, histologic type, or locoregional stage between those with a benign versus a malignant mass. However, the malignant masses were significantly larger (3.8 +/- 1.9 cm; range 2.5 to 7.1; median 3.1) than the benign masses (2.0 +/- 0.4 cm, range 1.2 to 2.8; median 2.0) (p < 0.001). Among those having magnetic resonance imaging (n = 25), the technique correctly predicted a malignant mass in the four patients with a histologically confirmed metastasis from non-small-cell lung cancer. However, among the 21 histologically benign masses, the magnetic resonance imaging was interpreted as benign in 5, malignant in 14, and indeterminate in 2. Therefore, although the false-negative rate was 0%, the false-positive rate was 67%. CONCLUSION: Most adrenal masses in patients with otherwise operable non-small-cell lung cancer are benign. Currently available magnetic resonance imaging methods cannot replace biopsy.

Adrenal Gland Diseases↗
PubMed1993

A prospective, randomized evaluation of the effect of silver impregnated subcutaneous cuffs for preventing tunneled chronic venous access catheter infections in cancer patients.

OBJECTIVE: This study was performed to evaluate the effect of a silver-impregnated cuff on the incidence of catheter-related bacteremia/fungemia or tunnel tract infection in cancer patients with chronic dual-lumen tunneled venous access catheters. SUMMARY BACKGROUND DATA: Infection is a frequent and potentially life-threatening complication of tunneled chronic cuffed silastic central venous access catheters in cancer patients. Recent experience with antimicrobial silver-impregnated cuffs placed on nontunneled percutaneously inserted central venous catheters suggests that such a cuff may render the catheter less prone to infection. METHODS: The authors prospectively randomized 200 cancer patients to receive either a dual-lumen 10 French tunneled cuffed silastic central venous access catheter or the same catheter with a second more proximal subcutaneous silver-impregnated cuff. All patients then were followed prospectively for infectious morbidity until the device was removed or the patient died. RESULTS: The hazard rate for infection/day (95% confidence limits) was 0.0022 (0.0015 to 0.0030) for standard catheters compared with 0.0027 (0.0019 to 0.0037) for catheters with silver-impregnated cuffs (p = not significant). Regression analysis of infection-free interval of both catheter types shows no difference over the lifetime of catheter as well as the over the first 48 days after insertion. CONCLUSIONS: The study indicated no effect of a silver-impregnated cuff in decreasing the incidence of catheter-related bacteremias/fungemias, tunnel infections, or the spectrum of causative microorganisms involved in cancer patients with tunneled chronic venous access catheters.

Adolescent↗
PubMed1992

A phase II trial of biochemical modulation using N-phosphonacetyl-L-aspartate, high-dose methotrexate, high-dose 5-fluorouracil, and leucovorin in patients with adenocarcinoma of unknown primary site.

BACKGROUND: 5-Fluorouracil (5-FU) has modest activity as a single agent in a number of human adenocarcinomas. The technique of biochemical modulation has been used preclinically to increase the activity of 5-FU. METHODS: With doses based on a Phase I study, the authors performed a Phase II trial in patients with advanced metastatic adenocarcinoma of an unknown primary site using N-phosphonacetyl-l-aspartate (PALA), methotrexate (MTX), 5-FU, and leucovorin. In some patients, 5-phosphoriosyl-l-pyrophosphate (PRPP) and uridine triphosphate (UTP) metabolite pools were assayed before and after PALA and MTX to assess metabolite pool shifts. RESULTS: Twenty-one patients were treated in this Phase II trial. Toxicity was tolerable. Biopsy specimens of tumor tissue showed increases in PRPP and decreases in UTP levels in two of three and three of four patients, respectively. However, only one objective response was seen, which is not different from that expected with 5-FU alone. CONCLUSIONS: Expected PRPP and UTP metabolite pool shifts were seen when biochemical modulation was performed with these drugs according to this schedule. Because toxicity was mild, more intense dose schedules of 5-FU are planned for future studies.

Adenocarcinoma↗
PubMed1992

Extraneural cysticercosis presenting as a tumor in a seronegative patient.

A case of cysticercosis involving only the sternocleidomastoid muscle of an otherwise-healthy pregnant woman is presented. An enzyme-linked immunoelectrotransfer blot assay for cysticercosis was nonreactive. The clinical features of extraneural cysticercosis are reviewed with special attention to musculocutaneous involvement. The results of serological tests for such patients may not be positive and histopathology remains the only reliable method for confirming the diagnosis of cysticercosis.

Adult↗
PubMed1991

Genetic organization and diversity of the hepatitis C virus.

The nucleotide sequence of the RNA genome of the human hepatitis C virus (HCV) has been determined from overlapping cDNA clones. The sequence (9379 nucleotides) has a single large open reading frame that could encode a viral polyprotein precursor of 3011 amino acids. While there as little overall amino acid and nucleotide sequence homology with other viruses, the 5' HCV nucleotide sequence upstream of this large open reading frame has substantial similarity to the 5' termini of pestiviral genomes. The polyprotein also has significant sequence similarity to helicases encoded by animal pestiviruses, plant potyviruses, and human flaviviruses, and it contains sequence motifs widely conserved among viral replicases and trypsin-like proteases. A basic, presumed nucleocapsid domain is located at the N terminus upstream of a region containing numerous potential N-linked glycosylation sites. These HCV domains are located in the same relative position as observed in the pestiviruses and flaviviruses and the hydrophobic profiles of all three viral polyproteins are similar. These combined data indicate that HCV is an unusual virus that is most related to the pestiviruses. Significant genome diversity is apparent within the putative 5' structural gene region of different HCV isolates, suggesting the presence of closely related but distinct viral genotypes.

Amino Acid Sequence↗
PubMed1991

Long-term vascular access via the inferior vena cava.

A prospective evaluation of long-term venous access catheters placed via the inferior vena cava was performed to determine their efficacy as well as short- and long-term morbidity. From June 1987 to May 1989, 31 catheters were placed in 26 patients, for a total of 3,503 catheter use days. All catheters were placed via an infraumbilical approach when the more conventional supraumbilical route was technically difficult, dangerous, or impossible to be used. There were a total of 14 complications in 12 episodes (one in every 701 catheter use days), six episodes of catheter occlusion or vessel thrombosis (one in every 583 catheter use days), one catheter malfunction, one episode of cuff erosion through the skin, and one catheter that migrated through the inferior vena cava into the retroperitoneum. These results compared favorably with our experience with long-term catheters of a similar type placed via a supraumbilical approach into the superior vena cava. We conclude that the infraumbilical route for long-term central venous access is safe and technically easy and should be strongly considered in patients in whom venous access via the supraumbilical approach will be technically difficult or have a high likelihood of failure.

Adolescent↗
PubMed1990

Prognosis of thick cutaneous melanoma of the trunk and extremity.

The records of 129 patients with thick cutaneous melanoma of the trunk or extremity treated at Memorial Sloan-Kettering Cancer Center, New York, NY, between 1974 and 1984 were reviewed with the aim of defining prognostic variables. All primary lesions invaded subcutaneous fat, were Clark level V, or of a Breslow thickness of 4.0 mm or greater. Treatment in all cases was by wide excision with or without split-thickness skin graft; all patients underwent regional lymph node dissection. Overall survival rate for the group was 47% at 5 years and 36% at 10 years. Factors independently predictive of survival were pathologic negative nodes (71% at 5 years compared with 28% for pathologic positive nodes) and extremity site (58% at 5 years compared with 33% for truncal site). Patients with node-negative thick cutaneous melanoma of the extremity had a 5-year survival rate of 82%. Patients with node-positive truncal thick cutaneous melanoma had a 5-year survival rate of only 8%. There was no difference between the 5-year survival rate of patients with node-negative truncal thick cutaneous melanoma, 52%, and patients with node-positive thick cutaneous melanoma of the extremity, 42%. Nearly half of the patients with thick cutaneous melanoma of the extremity and trunk present with locoregional disease, at a stage when an aggressive surgical approach is warranted. Prognostic variables of pathologic nodal status and site identify patients at risk for early systemic failure.

Age Factors↗
PubMed1990

A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma: effects of tumor burden and antigen expression.

Eighteen patients with relapsed non-Hodgkin's lymphoma (NHL) were infused with escalating doses of monoclonal antibody (mAb) OKB7, trace-labeled with iodine-131 (131I), in order to study toxicity, pharmacology, antibody localization, and dosimetry of radioiodine. OKB7 is a noncytotoxic mouse immunoglobulin G2b (IgG2b) mAb reactive with B cells and most B-cell NHL. Three patients each were treated at six dose levels ranging from 0.1 mg to 40 mg. All patients had radionuclide imaging and counting daily, had serial blood sampling to study pharmacokinetics, human antimouse antibody (HAMA), and circulating antigen, and had a biopsy of accessible lymphoma to determine delivery of isotope to tumors and assess the effect of tumor antigen expression on mAb delivery. Bone marrow biopsies were also done in the majority of patients. There was no toxicity. Serum clearance showed a median early phase half-life of 1.9 hours and a later phase half-life of 21.7 hours. Median total body clearance half-life was 22 hours. Pharmacokinetics were not dose-related. HAMA was detected in five patients. Circulating blocking antigen was detected in the serum of four patients, but at levels that were of pharmacologic consequence only in one. Biopsied tumor tissue from five patients did not express OKB7 antigen. No significant uptake of antibody was seen in these tumor sites. Mean total uptake of isotope into lymphoma measured in biopsies correlated linearly over the 400-fold increase in injected mAb dose. However, the percent of injected dose found per gram of tumor was unrelated to dose, but correlated inversely with tumor burden. In two patients with minimal tumor burden, 1.0 mg and 5.0 mg doses of OKB7 resulted in tumor to body radioisotope dose ratios of 22 and 7, which would theoretically permit tolerable delivery of 4,400 and 1,400 rads to these tumors, respectively, if OKB7 were conjugated with higher doses of 131I.

Adult↗
PubMed1988

Resolution of the two components of macrophage inflammatory protein 1, and cloning and characterization of one of those components, macrophage inflammatory protein 1 beta.

A number of macrophage-derived mediators have been implicated in the vascular changes of inflammation. We recently reported the isolation of a novel monokine, macrophage inflammatory protein 1 (MIP-1), which causes local inflammatory responses in vivo, and induces superoxide production by neutrophils in vitro. Purified native MIP-1 comprises two peptides with very similar physical characteristics. We report here the resolution of MIP-1 into component peptides by SDS-hydroxylapatite chromatography, and compare the NH2-terminal sequences of the two peptides, now referred to as MIP-1 alpha and MIP-1 beta. A synthetic oligonucleotide probe pool corresponding to the NH2-terminal amino acid sequence of MIP-1 beta was used to isolate a cDNA clone containing its coding sequence. The sequence codes for a 109 amino acid-long polypeptide, of which 69 amino acids correspond to the mature product. Comparison of this MIP-1 beta cDNA with our previously cloned MIP-1 alpha sequence reveals that the MIP-1 peptides, members of a growing family of potential inflammatory mediators, are distinct but highly homologous (58.9% sequence identity) products of different genes.

Animals↗
PubMed1988

Synthesis and assembly of a functionally active recombinant platelet-derived growth factor AB heterodimer.

A Chinese hamster ovary cell line that stably expresses transfected human platelet-derived growth factor (PDGF) A and B chain precursors was established. All three dimeric combinations of PDGF chains were produced by this cell line; their biosynthesis, assembly, and processing were followed by pulse-chase analyses. PDGF-AA, PDGF-AB, and PDGF-BB were processed to Mr values of about 30,000 and were accumulated in these forms in the medium. In addition, PDGF-BB was further processed to a 24-kDa component, which remained cell-associated. The major secreted component was PDGF-AB, which was purified and shown to have structural and functional characteristics indistinguishable from PDGF-AB purified from human platelets.

Animals↗
PubMed1988

Cloning and characterization of a cDNA for murine macrophage inflammatory protein (MIP), a novel monokine with inflammatory and chemokinetic properties.

In the course of studies on cachectin/TNF being conducted in our laboratory, a novel macrophage product has been detected and characterized. Termed macrophage inflammatory protein or MIP, this protein appears to be an endogenous mediator of the inflammatory events induced by endotoxin. A cDNA cloned probe for this protein has been isolated from a lambda gt10 phage library prepared from poly(A)+ RNA obtained of endotoxin-induced RAW264.7 cells. The sequence codes for a 92 amino acid-long polypeptide, of which 69 amino acids correspond to the mature product. The sequence predicts a molecular weight of 7,889 and structural analysis of the protein indicates a characteristic signal sequence alpha-helix and a hydrophobic core. Sequence data also confirm no sequence similarity to any other protein listed in the Dayhoff data base.

Amino Acid Sequence↗
PubMed1983

Chemical synthesis of a gene for human epidermal growth factor urogastrone and its expression in yeast.

We have chemically synthesized and expressed in yeast a gene coding for human epidermal growth factor (urogastrone), a 53-amino-acid polypeptide that has been shown to promote epithelial cell proliferation and to inhibit gastric acid secretion. The synthetic gene, consisting of 170 base pairs, was designed with yeast-preferred codons and assembled by enzymatic ligation of synthetic fragments produced by phosphoramidite chemistry. The DNA synthesis protocol used allows for facile synthesis of oligonucleotides larger than 50 bases. Yeast cells were transformed with plasmids containing the synthetic gene under control of a yeast glyceraldehyde-3-phosphate dehydrogenase gene promoter and were shown to synthesize a biologically active human epidermal growth factor.

Amino Acid Sequence↗
PubMed1981

Human prolactin. cDNA structural analysis and evolutionary comparisons.

Prolactin (Prl), growth hormone, and chorionic sommatomammotropin form a set (the "Prl set") of hormones which is thought to have evolved from a common ancestral gene. This assumption is based on several lines of evidence: overlap in their biological and immunological properties, similarities in their amino acid sequences, and homologies in the nucleic acid sequences of their structural genes. In the current study we report the cloning, amplification in bacteria, and sequence analysis of DNA complementary to Prl mRNA isolated from human pituitary Prl-secreting adenomas. The cloned DNA contains 914 bases, which includes the entire coding sequence of human prePrl as well as portions of the 5- and 3'-untranslated regions of the mRNA. The amino acid sequence predicted by our data differs from a previously reported amino acid sequence in 8 positions. With the results of this study we can now compare in one species the nucleotide sequences of the structural gene coding for each of the hormones of the Prl set. The sequence divergence at replacement sites is used to establish an evolutionary clock for the Prl set of genes. Using this clock, we postulate that the chromosomal segregation of human Prl and human growth hormone occurred about 392 million years ago and that growth hormone and chorionic sommatomammotropin underwent an intrachromosomal recombination within the last 10 million years.

Adenoma↗
PubMed1981

Cloning of bovine prolactin cDNA and evolutionary implications of its sequence.

Prolactin, growth hormone, and chorionic somatomammotropin (placental lactogen) constitute a set of related polypeptides believed to derive from a common evolutionary ancestor protein. We have cloned and sequenced DNA complementary to the mRNA coding for bovine prolactin. This cDNA contains 702 bases corresponding to 10 amino acids in the leader peptide, all 199 amino acids of the hormone, and 75 nucleotides in the 3' untranslated region of the mRNA. Nucleotide sequence analysis of this cDNA permitted the identification of 10 amino acids in the signal peptide, plus the correction or elucidation of amino acid assignments at 16 sites where aspartic and glutamic acids had not been distinguished from their amides by amino acid sequencing. Codon usage in bovine prolactin mRNA is nonrandom, but, similarly to rat and human prolactins, it does not exhibit the strong preference for G or C in codon third positions seen in bovine, rat, and human growth hormone mRNAs. The translational termination signal in bovine prolactin in UAA, also the same as in rat and human prolactins and differing from the UAG "stop" codon used in bovine, rat, and human growth hormones and human chorionic somatomammotropin. The amino acid and mRNA nucleotide sequences of bovine, rat, and human prolactins and growth hormones were compared by several techniques based on various theories of molecular evolution. The comparison of prolactin to growth hormone is consistent in all three species, suggesting that the genes for these two hormones diverged about 350 million years ago. However, comparisons among the three prolactins or among the three growth hormones to determine the times of evolutionary divergence of the three species generated values that were inconsistent with each other and with the fossil record. Analysis of these discrepancies suggests that the genes for prolactin and growth hormone may now be evolving by different mechanisms.

Amino Acid Sequence↗