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Biomedical subjects

N D Goldman

Publications and source records attributed to N D Goldman.

At least 19 recordsLinked to original sources
PubMed2001

Cost of nonmelanoma skin cancer treatment in the United States.

BACKGROUND: Despite being the most prevalent form of cancer, the economic impact of nonmelanoma skin cancer (NMSC) in the United States has not been assessed. OBJECTIVE: To determine the overall cost and to estimate the cost per episode of NMSC care in the United States in physicians' offices, outpatient surgery centers, and inpatient settings. METHODS: Data from the Medicare Current Beneficiary Study 1992-1995 were analyzed to obtain the total cost of NMSC and the cost in different settings. To normalize these data on a per episode basis, the cost in each setting was divided by the number of procedures performed in each setting obtained from the National Hospital Discharge Survey (NHDS, 1992-1997), the National Survey of Ambulatory Surgery (NSAS, 1994-1996), and the National Ambulatory Medical Care Survey (NAMCS, 1995). RESULTS: The total cost of NMSC care in the United States in the Medicare population is $426 million/year. Physician office-based procedures for NMSC accounted for the greatest percentage of money spent to treat NMSC and the greatest percentage of procedures. The average cost per episode of NMSC when performed in a physician's office setting was found to be $492. The cost per episode of care in inpatient and outpatient settings were $5537 and $1043, respectively. CONCLUSION: Compared to other cancers, the relative magnitude of NMSC treatment costs is currently small because NMSC is managed efficiently and effectively, primarily in office-based settings. Legislative or regulatory measures that discourage office treatment of NMSC will lead to increased cost.

Ambulatory Surgical Procedures↗
PubMed2000

Meta-analysis in otolaryngology.

OBJECTIVE: To examine the results of meta-analyses in otolaryngology and compare these results with the individual component studies that constitute each meta-analysis. DESIGN: A retrospective review of the literature. MAIN OUTCOME MEASURES: Studies that conducted pooled statistical systematic analyses indexed on MEDLINE for the 10-year period from January 1989 to January 1999 were selected for keyword or subject headings of meta-analysis and otolaryngology (N = 22). Analysis consisted of a modified funnel graph depiction of the individual studies that made up each meta-analysis. Each meta-analysis was evaluated for consistency among these individual studies and comparison of the median result with the weighted mean meta-analysis result. In addition, the methodologic quality of each meta-analysis was assessed in terms of the rigor with which component studies were evaluated. RESULTS: Ten (46%) of the 22 meta-analyses did not provide the individual study results that made up their meta-analyses. The results of 10 studies (46%) were similar to the median result of their individual component studies. The results of 2 studies (9%) differed from this median result, with widely heterogeneous component study results. CONCLUSIONS: A large proportion of meta-analyses in otolaryngology (46%) fail to provide the individual study results necessary to analyze the meta-analysis result critically. Most remaining studies do provide results that accurately compare with the median of their component study results. Only a small proportion of meta-analyses were found to have disparate results, and each appropriately discusses the heterogeneity of the individual studies that comprise their meta-analysis.

Evaluation Studies as Topic↗
PubMed1999

Molecular cloning and nuclear localization of a histone deacetylase homologue in Plasmodium falciparum.

Reversible acetylation of core histones plays an important role in transcriptional regulation, cell cycle progression and developmental events. The acetylation state of histones is controlled by a dynamic equilibrium between activities of histone acetylase and deacetylase enzymes. Histone deacetylase (HDAC) was recently suggested to be the target of a fungus-derived antiprotozoal agent exhibiting structural similarity to known HDAC inhibitors. We have initiated a study of HDAC of human malaria parasite, Plasmodium falciparum, to evaluate its potential as the target for novel antimalarials and its role in parasite development. We have isolated HDAC1 gene from the P. falciparum genomic and cDNA libraries. The nucleotide sequence contains no intervening sequence and its open reading frame (ORF) codes for a protein of 449 amino acid residues. We have named the protein, PfHDAC1, as the sequence shows significant homology to yeast, human and other eukaryotic HDACs. Northern blot analysis of the total RNA from different asexual and sexual stages of the parasite reveals the presence of single mRNA transcript, which is predominantly expressed in mature asexual blood stages and in gametocytes. Antiserum raised against a carboxyl terminal peptide immunoprecipitated an in vitro translated P. falciparum HDAC gene product and recognized an approximately 50 kDa protein in the Triton X-100 insoluble fraction of parasites. Immunoelectron microscopy analysis showed majority of the protein localized in the nucleus of P. falciparum. To our knowledge, this is the first HDAC gene isolated from the malaria parasite.

Amino Acid Sequence↗
PubMed1999

Isolated intracranial mucocele.

Intracranial mucoceles have been previously reported as direct extradural extensions of mucoceles of the paranasal sinuses. We describe a patient with 2 silent mucoceles isolated within the parenchyma of the frontal lobe of the brain. The patient had undergone multiple previous intranasal polypectomy and ethmoidectomy procedures, and the unsuspected mucoceles were discovered on a computed tomographic scan obtained to evaluate recurrent rhinosinusitis symptoms. Craniotomy was required for removal of the mucoceles.

Brain Diseases↗
PubMed1999

Expression and characterisation of a Plasmodium falciparum protein containing domains homologous to sarcalumenin and a tyrosine kinase substrate, eps15.

We have identified in Plasmodium falciparum a novel gene encoding a putative bi-functional protein, termed PfPast-1, from genomic and cDNA libraries. Analysis indicated that the sequence encodes a 62 kDa protein of 529 amino acid residues with two distinctive domains: a sarcalumenin-like domain of approximately 320 amino acids at the amino half of the molecule, which shares homology to a major sarcoplasmic reticulum lumenal protein, sarcalumenin, and an eps15 homology domain of about 90 amino acids located at the carboxyl terminus. The eps15 homology domain, first identified in a tyrosine kinase substrate, eps15, and found in increasing numbers of mammalian proteins, has recently been suggested as a protein-protein interaction domain involved in intracellular sorting. Genomic sequences encoding similar proteins containing both the sarcalumenin-like and eps15 homology domains have been identified in humans and Drosophila. RNA blot analysis revealed the presence of a single messenger RNA transcript approximately 3.7 kb in size, which is expressed in all the developmental stages examined with the highest level in extracellular gametes followed by erythrocytic asexual stages, and the lowest in the gametocytes. In the attempt to define its biological function, we have expressed a full-length recombinant PfPast-1 protein in Escherichia coli. Specific immune serum directed against the recombinant protein recognised a approximately 55 kDa protein in the parasite lysate. Further characterisation of PfPast-1 may help in elucidation of its functions in P. falciparum.

Amino Acid Sequence↗
PubMed1996

Regulation of human C-reactive protein gene expression by two synergistic IL-6 responsive elements.

To study the mechanism of interleukin-6 (IL-6) induction of human C-reactive protein (CRP) gene expression, we have utilized a human hepatoma (PLC/PRF/5) cell culture system to analyze the trans-acting factors which bind to the 300 bp 5'-flanking region of human CRP gene. In vitro gel mobility shift analyses and methylation interference assays demonstrated that NFIL-6 alpha interacted with two IL-6 responsive elements, and HNF-1 alpha and HNF-3/Octamer-like factors interacted with the downstream IL-6 responsive element in the human CRP promoter. In vivo functional analysis by transient transfection of plasmid constructs containing site-specific mutations in one or two IL-6 responsive elements in the CRP promoter fused to a reporter gene, chloramphenicol acetyl transferase (CAT), demonstrated that the binding of NFIL-6 alpha to two IL-6 responsive elements resulted in synergistic induction of the gene. When HNF-1 alpha or HNF-3/Octamer-like factors were independently bound to their corresponding sites, they had either a positive or negative effect, respectively, on IL-6 inducible transcriptional activity.

Base Sequence↗
PubMed1996

Cloning of a Plasmodium falciparum gene related to the human 60-kDa heat shock protein.

We have identified a gene encoding the 60 kDa heat shock protein (hsp60) from a Plasmodium falciparum blood stage cDNA library. The deduced protein sequence encodes for a polypeptide of 577 amino acids with a calculated molecular weight of 62158 Da. The primary structure of P. falciparum hsp60 contains a putative mitochondrial targeting peptide at its amino-terminus and a GGM motif at its carboxyl-terminus. The overall structure exhibits strong conservation (approximately 50%) to the hsp60 from human and other eukaryotes, but only low homology (< 30%) to a recently reported P. falciparum chaperonin 60 gene. The P. falciparum hsp60 gene is located on chromosome 10. During heat shock, the level of hsp60 transcript in blood stage parasites increases significantly and its accumulation correlates with the duration of the induction.

Amino Acid Sequence↗
PubMed1996

Stage-specific expression of a Plasmodium falciparum protein related to the eukaryotic mitogen-activated protein kinases.

We have identified a putative protein kinase gene from both Plasmodium falciparum cDNA and genomic DNA libraries. The nucleotide sequence contains an open-reading frame of 2646 bp, which codes for a predicted protein of 882 amino acid residues. Comparison of the predicted amino acid sequence with those in GenBank suggests that this gene codes for a protein similar to the mitogen-activated protein (MAP) kinase of other organisms. This MAP kinase-related protein, named PfMRP, contains the TDY dual phosphorylation site upstream of the highly conserved VATRWYRAPE sequence in subdomain VIII. PfMRP contains an unusually large and highly charged domain within its carboxyl-terminal segment, which includes two repetitive sequences of either a tetrapeptide or octapeptide motif. PfMRP gene is located on chromosome 14. Northern blot analysis of total RNA reveals the presence of a single mRNA transcript approximately 4.2 kb in length, which is predominantly expressed in gametocytes and gametes/zygotes.

Amino Acid Sequence↗
PubMed1996

Thyroid cancers. I. Papillary, follicular, and Hürthle cell.

The well differentiated thyroid carcinomas, papillary, follicular, and Hürthle cell, comprise the majority of malignant thyroid diseases. This article presents guidelines for the evaluation and treatment of these malignancies. Prognostic factors, surgical treatment of the thyroid and regional lymph nodes, postoperative detection of recurrence, and treatment of distant metastases are discussed.

Adenocarcinoma↗
PubMed1995

Microtia repair.

Management of microtia can be one of the most rewarding yet humbling challenges faced by the reconstructive surgeon. The preferred method of total auricular reconstruction is with autologous cartilage and skin, based on modifications of the methods of Tanzer and Brent. Our goals in auricular reconstruction of microtia are: (1) a satisfied patient; (2) proper positioning; and (3) a pleasing size and contour. The reconstructive process in classic microtia reconstruction can be divided into four stages. The first stage is the creation and placement of the underlying framework derived from the autologous rib cartilage of the sixth to eighth ribs. The second stage is rotation of the lobule from the microtia remnant into position inferiorly on the helical rim. The third stage is elevation by creation of an auriculocephalic angle with a skin graft. The final stage is formation of the tragus from a composite graft from the opposite ear. Atypical microtia presents distinct challenges to the reconstructive surgeon. Complete framework insertion may not be necessary with the presence of some recognizable structure. Other circumstances arise that make each reconstruction unique, such as low-lying hairline or skin shortage. The extreme situations of skin shortage will benefit from the use of a temporoparietal fascia flap. However, adherence to the well-established principles of total auricular reconstruction will lead to satisfaction of the patient, the patient's family, and the surgeon.

Cartilage↗
PubMed1990

cis-acting elements responsible for interleukin-6 inducible C-reactive protein gene expression.

To study the mechanism of induction of human C-reactive protein (CRP) gene expression, we have utilized an in vitro liver cell system to analyze the cis-acting DNA sequences located within the 5'-flanking region of human CRP gene. Stable transfection of human hepatoma cells, PLC/PRF/5, by a CRP gene construct containing the 1 kilobase pair of upstream sequence of the CRP gene demonstrated that this region contained the inducible element(s) which regulated human CRP gene transcription. Dissection of this region by 5', 3' and internal deletion constructs of upstream region of the CRP gene fused to a reporter gene, chloramphenicol acetyl transferase, indicated the presence of two inducible elements located proximal to the site of initiation of transcription, two constitutive enhancer-like elements located distal to the promoter, and a negative regulatory region located between the two inducible elements. We had previously shown that a protein factor from monocytes or HTLV1-infected T-cells, was responsible for CRP induction in hepatoma cells. We have found this factor to be synonymous with interleukin-6. By stable and transient transfection assays in hepatoma cells, recombinant interleukin-6 alone was sufficient to activate both inducible elements.

Base Sequence↗
PubMed1990

Biochemical and biological analysis of human interleukin 6 expressed in rodent and primate cells.

The cDNA for human interleukin 6 (IL 6) was stably expressed at high levels in the three mammalian cell lines COS-7, PA317, and GH3 to yield IL 6 proteins of 25 to 27, 26, 22 to 24, and 23 kDa molecular mass. Both size and relative amounts of the recombinant IL 6 (rIL 6) species produced correspond to those of natural IL 6 secreted by LPS-stimulated monocytes. Oligosaccharide analysis of recombinant IL 6 utilizing tunicamycin and endoglycosidases revealed O- and N-linked glycosylation that is comparable to that of natural IL 6 derived from human monocytes and fibroblasts. IL 6 expressed in each of the three cell lines was phosphorylated similarly to the IL 6 produced in human monocytes and fibroblasts. IL 6 secreted by the three different cell lines have marked differences in specific biological activities. COS-7 IL 6 appeared to be 12-fold more active in its hybridoma growth factor activity than that made in PA317 or GH3 cells. In contrast, PA317 and GH3 IL 6 were 230 and 6.7 times more effective than COS-7 IL 6 in inducing Ig production in CESS cells. Also, PA317 and GH3 IL 6 were more effective than COS-7 IL 6 in inducing the acute-phase protein fibrinogen in human hepatocytes. The rIL 6 species exhibited no antiviral activity.

Acute-Phase Proteins↗
PubMed1988

Monocyte-derived human B-cell growth factor identified as interferon-beta 2 (BSF-2, IL-6).

Soluble products of either Epstein-Barr virus (EBV)-infected B cells or activated monocytes promote the proliferation of EBV-infected B cells and permit their growth at low cell densities. This suggests that growth factors are important for B-cell immortalization by EBV. In this study, a monocyte-derived factor that promotes the growth of EBV-infected b cells was purified and identified as interferon-beta 2 (IFN-beta 2), which is also known as 26-kilodalton protein, B-cell differentiation factor (BSF-2), and interleukin-6 (IL-6). The purified protein has a specific activity of approximately 4 X 10(7) units per milligram of protein in assays of B-cell growth. Thus, IFN-beta 2/BSF-2 is a B-cell growth factor that promotes the proliferation of human B cells infected with EBV.

B-Lymphocytes↗
PubMed1987

Structural analysis of the locus containing the human C-reactive protein gene and its related pseudogene.

The gene for human C-reactive protein (CRP) is mapped within a 34-kilobase pair genomic DNA segment identified by chromosome walking through overlapping DNA fragments cloned into a lambda phage library. Within 16 kilobase pairs upstream and downstream of the locus for the authentic CRP gene, only one other sequence homologous to that for CRP could be found. Sequencing analysis indicates this sequence to be a pseudogene with 50-80% region-specific homology. Comparison of the authentic CRP gene cloned from genomic DNA libraries independently prepared from three patients indicates no difference in the 5' and 3' flanking region, promoter region, or coding sequence. Only a polymorphism in the length of the poly(GT) stretch located in the intron is observed. There appears to be only one gene locus and copy per haploid chromosome for the authentic CRP gene and its pseudogene.

Bacteriophage lambda↗
PubMed1987

Biosynthesis of human C-reactive protein in cultured hepatoma cells is induced by a monocyte factor(s) other than interleukin-1.

An in vitro cell culture system utilizing continuous human liver cells has been developed which, upon specific induction, will respond by synthesizing, de novo, the prototype acute phase reactant, C-reactive protein (CRP). Induction of CRP in vitro is not brought about by the types of hormones, steroids, and chemicals which affect other acute phase proteins. In particular, interleukin-1 thought to be directly responsible for acute phase induction is not found to be active. Direct testing of other purified biological response modifiers, i.e. alpha, beta, and gamma-interferon, interleukin-2, and tumor necrosis factor, demonstrates no inducing activity. However, we find that human peripheral blood monocytes, stimulated by endotoxin, produce a factor(s) which directly induces CRP synthesis in hepatoma cells. In addition, the human promyelocyte-like cell line HL-60 in the presence of phorbol ester and certain T-cell lines containing human retroviruses also produce this CRP-inducing factor(s). Isolation and partial purification of the CRP-inducing factor(s) indicate that it is a protein(s) with a molecular weight of approximately 30,000.

C-Reactive Protein↗
PubMed1985

Genomic DNA sequence for human C-reactive protein.

The gene for the prototype acute phase reactant, C-reactive protein, has been isolated from two lambda phage libraries containing inserted human DNA fragments using synthetic oligonucleotide probes. Nucleotide sequence analysis indicates that after coding for a signal peptide of 18 amino acids and the first two amino acids of the mature protein, there is an intron of 278 base pairs followed by the nucleotide sequence for the remaining 204 amino acids. The intron is unusual in that it contains on the positive strand a poly(A) stretch 16 nucleotides long and a poly(GT) region 30 nucleotides long which could adopt the Z-form of DNA. The nucleotide sequence reported here confirms the amino acid sequence of mature C-reactive protein as originally reported except that it codes for an additional 19 amino acids beginning at position 62. Thus DNA sequence analysis predicts that the mature protein consists of 206 amino acids rather than 187 as originally reported. The mRNA cap site is located 104 nucleotides from the start of the signal peptide and there is a 3' noncoding region 1.2 kilobase pairs in length. The gene has a typical promoter containing the sequences TATAAAT and CAAT 29 and 81 base pairs upstream, respectively, of the cap site.

Amino Acid Sequence↗
PubMed1985

A monoclonal antibody 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac.

Murine splenocytes immune to influenza virus-activated human T-cells were fused with SP2/0 cells, selected in chemically defined HAT media, and subcloned to yield a monoclonal antibody (MAb) termed 7G7/B6. 7G7/B6 binds to lectin- and antigen-activated T-cells, but not resting T-cells or B-lymphoblastoid lines from the same donor. 7G7/B6 immunoprecipitates a 50-55 kD band from cell surface iodinated PHA-activated T-cells or the T-cell leukemia line HUT 102B2, as shown on SDS-PAGE. Cross-clearing studies demonstrate that 7G7/B6 binds the same cell surface molecule(s) as anti-Tac, a MAb which has been shown previously to recognize the human receptor for IL-2. 35S-methionine pulse chase experiments in HUT 102B2 cells reveal that 7G7/B6 binds to an early (less than 30 min) 35-37 kD and late (greater than 4 h) 50 kD protein. Sequential immunoprecipitations demonstrate that these are identical to the molecules identified by anti-Tac under similar conditions. However, only anti-Tac coprecipitates a higher molecular band at 110 kD. 7G7/B6 and anti-Tac do not competitively inhibit the binding of each other to PHA-activated T-cells. Functional studies reveal that in contrast to anti-Tac, 7G7/B6 has almost no inhibitory effect in vitro on IL-2-driven proliferation of IL-2-dependent T-cell lines, or alloimmune cytotoxic T-cell generation (however, once generated, these cytotoxic T-cells were both 7G7/B6 and anti-Tac positive). Finally, IL-2 does not inhibit the binding of 7G7/B6 to activated T-cells under conditions which result in up to 75% inhibition of anti-Tac binding. Therefore, 7G7/B6 is another MAb recognizing the human IL-2 receptor, but binding to an epitope distinct from that recognized by either IL-2 or anti-Tac.

Antibodies, Monoclonal↗