Medilas Nd:YAG laser in oral cavity cancer.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
D D Patel
Publications and source records attributed to D D Patel.
Plasma prolactin as an indicator of disease progression in advanced breast cancer.
Serial plasma prolactin levels were measured in 144 breast cancer patients (premenopausal [PR-M], N = 64; postmenopausal [PO-M], N = 80) and compared with respective controls. Patients with breast cancer were grouped into those who (1) developed distant metastasis, (2) developed local recurrence, (3) stable disease, and (4) responded to the various therapeutic modalities at the end of 2 years. The authors' analysis showed excellent correlation between serial plasma prolactin changes and the response to therapy or progression of disease in patients with advanced breast carcinoma.
Biomarkers, Tumor↗
Fine structure mapping and phenotypic analysis of five temperature-sensitive mutations in the second largest subunit of vaccinia virus DNA-dependent RNA polymerase.
We have used plasmid clones spanning the region encoding the 132-kDa subunit of the cowpox virus RNA polymerase (CPV rpo 132) to marker rescue each of five vaccinia virus (VV) temperature sensitive (ts) mutants, ts 27, ts 29, ts 32, ts 47, and ts 62, which together constitute a single complementation group. The experiments fine-map the vaccinia mutations to a 1.3-kb region containing the 3' end of the CPV rpo 132 gene. Phenotypic characterization shows that all five mutants are affected to varying extents in their ability to synthesize late viral proteins at the nonpermissive temperature, similar to other ts mutants with lesions in the 22- and the 147-kDa subunits of the VV RNA polymerase. Two mutants, ts 27 and ts 32, exhibit a delay in the synthesis of late viral proteins at both the permissive and the nonpermissive temperatures. We conclude that the five VV mutants affect the 132-kDa subunit of the VV RNA polymerase. Additional genetic experiments demonstrate intragenic complementation between ts 62 and three other members of this complementation group, ts 27, ts 29, and ts 32.
Animals↗
Defective processing and binding of low-density lipoprotein receptors in fibroblasts from a familial hypercholesterolaemic subject.
The properties of the low-density lipoprotein (LDL) receptor were studied in skin fibroblasts from a homozygous familial hypercholesterolaemic subject, MM (MM cells), who exhibits a defect in the processing of the precursor form of the receptor. Despite the prolonged half-life of the precursor (3 h), essentially all was eventually processed to the mature form, which was degraded with a half-life of approximately 6 h. The receptor content of the MM cells, determined by radioimmunoassay, was slightly lower than normal and by immunoblotting it was estimated that 55% was present as the mature form at equilibrium. The mature receptor reached the cell surface and was internalized and recycled apparently normally, with about 60% accessible to pronase at any time. Immunoblotting, immunoassay and surface labelling with 125I all indicated that the cells contained twice as much surface receptor protein as would be expected from the binding of LDL. Maximum heparin-releasable LDL binding to MM cells was 20% of normal and the apparent affinity for LDL was reduced. The cells did not show the marked increase in affinity and reduction in binding exhibited by normal cells when cooled to 4 degrees C. Also, neither the apparent affinity of the receptors nor the maximum binding at 37 degrees C was greatly affected by an antibody that has been shown to reduce the affinity and halve the binding of normal cells. The results suggest that the mutation in the LDL receptor gene of these cells affected the ability of the receptors to bind LDL in a similar manner to the antibody, possibly by promoting aggregation of receptors on the cell surface, and halving the amount of LDL bound.
Adult↗
Identification of a point mutation in growth factor repeat C of the low density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia that affects ligand binding and intracellular movement of receptors.
The coding region of the low density lipoprotein (LDL)-receptor gene from a patient (MM) with homozygous familial hypercholesterolemia (FH) has been sequenced from six overlapping 500-base-pair amplified fragments of the cDNA from cultured skin fibroblasts. Two separate single nucleotide base changes from the normal sequence were detected. The first involved substitution of guanine for adenine in the third position of the codon for amino acid residue Cys-27 and did not affect the protein sequence. The second mutation was substitution of thymine for cytosine in the DNA for the codon for amino acid residue 664, changing the codon from CCG (proline) to CTG (leucine) and introducing a new site for the restriction enzyme PstI. MM is a true homozygote with two identical genes, and the mutation cosegregated with clinically diagnosed FH in his family in which first cousin marriages occurred frequently. The amino acid change occurs in the center of growth factor repeat C in the epidermal growth factor precursor-homology domain of the protein, a region of highly conserved sequence between bovine and human LDL receptors, and results in slowed, but complete, maturation of the precursor to the mature form of the receptor and, despite its remoteness from the ligand-binding domain, in impaired binding of LDL. LDL receptors in MM's skin fibroblasts bind less LDL than normal and with reduced affinity. Thus this naturally occurring single point mutation affects both intracellular transport of the protein and ligand binding and occurs in growth factor-like repeat C, a region that has not previously been found to influence LDL binding.
Amino Acid Sequence↗
The second-largest subunit of the poxvirus RNA polymerase is similar to the corresponding subunits of procaryotic and eucaryotic RNA polymerases.
We have characterized the poxvirus gene encoding the second-largest subunit of the viral DNA-dependent RNA polymerase. This gene, designated rpo132, is located in the HindIII A fragment of the DNA of the Brighton Red strain of cowpox virus. A similar gene is located in the corresponding position in the HindIII A fragment of the DNA of the Western Reserve strain of vaccinia virus. The rpo132 gene is transcribed throughout the viral multiplication cycle. It has two transcriptional start sites; one is operative at late times only, and the other (80 base pairs downstream) is operative both at early times and at late times. Neither early nor late transcripts originating from the latter RNA start site contain long 5'-terminal poly(A) sequences. The rpo132 gene has the capacity to encode primary gene products of two types. The RNA transcripts whose 5' ends correspond to the early RNA start site can encode a 133-kilodalton (kDa) protein. The RNA transcripts whose 5' ends correspond to the early RNA start site can encode a 132-kDa protein. Transcripts of the latter type are more abundant, suggesting that the 132-kDa protein is the major primary product of this gene. The predicted amino acid sequences of both gene products share extensive similarities with the amino acid sequences of the second-largest subunits of the following enzymes: the RNA polymerase of Escherichia coli, the RNA polymerase II of Saccharomyces cerevisiae, and the RNA polymerase II of Drosophila melanogaster. This result provides further evidence of relatedness between multisubunit DNA-dependent RNA polymerases.
Amino Acid Sequence↗
Surgically removed adrenal myelolipoma with pre-operative diagnosis--a case report.
Explore the source record for details and available documents.
Adrenal Gland Neoplasms↗
Low-density-lipoprotein-receptor mRNA content of fibroblasts from normal and familial hypercholesterolaemic subjects.
The amount of mRNA for the low-density-lipoprotein (LDL) receptor in cultured human fibroblasts was estimated by hybridization of the poly(A)-rich RNA fraction with a DNA probe, using the recovery of beta-actin mRNA to correct for losses. During incubation of the cells with lipoprotein-deficient serum (LPDS) both the LDL-receptor mRNA content and the rate of receptor protein synthesis increased fourfold during the first 16 h and then fell by approximately 50% during the next 24 h. The content of beta-actin mRNA fell by a similar amount, so that the ratio of receptor/beta-actin mRNAs rose and then remained constant. The fall in beta-actin mRNA content during incubation with LPDS was not prevented by the addition of cholesterol to the medium. In cells from a homozygous familial hypercholesterolaemic (FH) subject that bound 20% of the normal amount of LDL, the content of LDL-receptor mRNA and the changes during incubation with LPDS or free sterols were similar to normal. Cells from a familial hypercholesterolaemic subject that produced no immunodetectable receptor protein produced a small amount of receptor mRNA of apparently normal size which responded in the same way as in normal cells to LPDS and free sterols.
Actins↗
Increased frequency of sister chromatid exchanges in lymphocytes of breast cancer patients.
Spontaneous and mitomycin-C (MMC)-induced rates of sister chromatid exchanges (SCEs) were studied in peripheral blood lymphocytes (PBLs) of 40 patients with cancer of the breast and 40 healthy female volunteers as controls. Spontaneous SCE per cell value in PBL cultures was 7.72 for the breast cancer patients, which was significantly higher (p less than 0.001) than the 6.28 SCEs per cell scored for the controls. Eight of the patients were studied a second time, 3 to 6 months following surgical removal of the tumour. A significant (p less than 0.05) reduction in SCE per cell value was observed following mastectomy. MMC-induced frequencies of SCE remained comparable in patients and controls. Cellular kinetics, calculated as average generation time (AGT) from the frequency of cells in M1, M2 and M3 cycles, were comparable in patients and controls.
Adult↗
An antibody to the low-density lipoprotein (LDL) receptor that partially inhibits the binding of LDL to cultured human fibroblasts.
A monoclonal antibody, raised initially against pure bovine low-density lipoprotein (LDL) receptor, was found to bind saturably to LDL receptors on the surface of cultured human fibroblasts. It was apparently internalized by the cells but rapidly returned to the surface and was not significantly degraded. LDL did not affect the binding of antibody. However, the antibody reduced both the apparent affinity of the receptor for LDL and the amount of LDL bound. In the presence of antibody, the concentration of LDL required for one-half maximum binding increased from 14.5 nM to 22.3 nM at 37 degrees C and from 2.8 nM to 11.5 nM at 4 degrees C. Maximum heparin-releasable binding of LDL was reduced by 56% at 37 degrees C and by 36% at 4 degrees C. Fab fragments halved the affinity at both temperatures without affecting the maximum amount of LDL bound. At 4 degrees C, maximum heparin-releasable LDL binding was the same as that of antibody and of Fab fragments. At 37 degrees C, heparin-releasable binding of LDL and binding of Fab fragments were double that at 4 degrees C, whereas binding of antibody remained unchanged. The results suggest that the antibody bound to a site on the receptor remote from the LDL binding region and that intact antibody recycled with the receptor. It halved LDL binding and degradation at 37 degrees C and reduced binding at 4 degrees C, probably through a different mechanism. The possibility that both cooling and antibody led to receptor aggregation is discussed.
Antibodies, Monoclonal↗
Virulence genes of poxviruses and reoviruses.
Identification of viral genes that specify virulence, however defined, is of critical importance for the design of viral vaccines. In particular, the targeted development not only of avirulent vaccine strains but also of viruses to be used as carriers for foreign genes depends on the inactivation or deletion of genes that harm the host. This paper illustrates approaches to identifying viral pathogenesis genes in two model systems involving cowpox virus and reovirus, respectively.
Base Sequence↗
A poxvirus-derived vector that directs high levels of expression of cloned genes in mammalian cells.
High levels of expression of cloned genes have been obtained in mammalian cells by using poxvirus-derived insertion/expression vectors. These vectors employ the cis-acting element (CAE I) that directs the transcription of one of the most strongly expressed genes of cowpox virus. This gene (the 160K gene) encodes the 160-kDa protein that is the major component of the A-type cytoplasmic inclusions. Its counterpart in vaccinia virus (VV) is the 94K gene contained in the HindIII A fragment of the viral DNA. Two insertion vectors have been constructed; each is designed to allow cloned genes to be placed immediately downstream of a modified version of CAE I within a poxvirus genome. One vector, p1200, enables the CAE I-cloned-gene constructs to be inserted into the thymidine kinase gene of VV. This vector was used to create a VV recombinant that directed expression of the chloramphenicol acetyltransferase (CAT) gene. The other vector, p2101, enables the CAE I-cloned-gene constructs to be inserted into the VV 94K gene. The prototype of this vector was used to create a VV recombinant that directed expression of a hybrid CAT-lacZ gene. Infection of cultured human cells with these recombinants led to high levels of synthesis of either the CAT gene product or the CAT-lacZ gene product. Each of these proteins was produced in quantities that were easily detected by Coomassie blue staining of total cell proteins resolved by polyacrylamide gel electrophoresis. We estimate that these vectors are capable of directing the synthesis of milligram amounts of gene product per 10(9) mammalian cells.
Animals↗
Correlation of steroid receptors with histopathologic characteristics in breast carcinoma.
Estrogen and progesterone receptors were correlated to histologic variables in 288 breast cancer patients from western India. The progesterone receptors (PR) were significantly elevated as compared to estrogen receptors (ER) amongst primary pre- and peri-menopausal breast carcinomas. ER positivity was correlated significantly to nuclear grade. Lymphatic invasion and vascular permeation were not found to be linked to ER, while PR positivity could be linked to lymphatic invasion and inversely to vascular permeation. Higher frequency of ER positivity was observed in lobular carcinomas. PR concentrations of the tumor had better correlations with histologic variables as compared to ER.
Adult↗
Serum sialic acid forms as markers for head and neck malignancies.
The value of protein-bound (PSA), lipid-bound (LSA) and free sialic acid (FSA) levels in the serum as marker was assessed together with its use as a prognostic indicator for head and neck cancers in 165 patients followed-up for over 18 months. Elevated PSA levels were found in 57% of patients with benign disorders, 52% with primary head and neck cancers, and 75% with metastatic cancer. Strong correlation was found between PSA and the regression/progression of the disease. The PSA level essentially returned to normal in patients with favorable prognosis and PSA levels showed a tendency to increase or remain at high levels in patients with a poor prognosis. These results suggest that PSA level is a better prognostic indicator in head and neck cancers, for which there is no available tumor marker.
Biomarkers, Tumor↗
Messenger RNAs of a strongly-expressed late gene of cowpox virus contain 5'-terminal poly(A) sequences.
We have identified and characterized one of the most strongly-expressed genes of cowpox virus (CPV). This is the gene encoding the major protein component of the A-type inclusion bodies produced by this virus. This gene (designated the 160K gene) is transcribed late during the infection. Analyses of its mRNAs showed that these late RNAs, unlike all other characterized late mRNAs of poxviruses, are uniform in length. However, the most remarkable feature of the mRNAs of the 160K gene is the structure of their 5'-termini. Most of these mRNAs have 5'-terminal poly(A) sequences containing 5-21 residues. Furthermore, these 5'-terminal poly(A) sequences are not complementary to the corresponding region of the template strand of the viral DNA. Instead, the nucleotide sequences of the mRNA and the viral DNA diverge at the site of the three As in the sequence 5'-TAAATG-3' containing the gene's initiation codon. Consequently, the poly(A) provides the leader sequences of these mRNAs. These unusual 5'-terminal structures suggest that the late mRNAs of pox-virus genes are generated by a novel process.
Amino Acid Sequence↗
Regulation of synthesis and cell content of the low-density-lipoprotein receptor protein in cultured fibroblasts from normal and familial hypercholesterolaemic subjects.
Incorporation of [35S]methionine into low-density-lipoprotein (LDL) receptors by normal fibroblasts and those from a homozygous familial hypercholesterolaemic (FH) subject who produced defective but immunoprecipitable receptor proteins of normal size, was compared with the ability of the cells to bind LDL and their content of LDL receptor protein determined using a double-antibody radioimmunoassay. The FH cells produced precursor protein with a longer half-life (3-4 h) than normal cells (40 min), most of which was eventually processed to a mature form of the receptor. Total receptor half-life was similar to normal (approx. 12 h) and LDL binding about 20% of normal. Incubation of normal fibroblasts with lipoprotein-deficient serum (LPDS) led to an increase in the amount of LDL receptor protein in the cells which was closely followed by the increase in their ability to bind LDL. Receptor synthesis increased rapidly at first, but then fell by more than 60% before remaining constant. The peak of synthesis coincided with the greatest rate of increase in receptor content. At equilibrium in LPDS receptor synthesis, LDL binding and receptor protein content were all approximately 3.3-fold higher than in cells maintained in 10% foetal calf serum (FCS). The FH cells also responded to LPDS with a rise and fall in the rate of receptor synthesis. They did not compensate for their inefficiency in producing active receptors with an increase in total receptor content. In LPDS, peak synthesis and maximum receptor content of the FH cells were similar to normal. In FCS receptor synthesis and content were well below maximum so that they did not fully employ even the low capacity for LDL uptake of which they were capable. With both types of cell, inhibition of mevalonic acid and cholesterol synthesis with compactin delayed, but did not prevent the secondary fall in the rate of receptor synthesis, again suggesting a regulatory role for some factor not directly related to cholesterol metabolism.
Acetates↗
Non-saturable degradation of LDL by monocyte-derived macrophages leads to a reduction in HMG-CoA reductase activity with little synthesis of cholesteryl esters.
In monocyte-derived macrophages from both normal and familial hypercholesterolaemic (FH) subjects, degradation of low density lipoprotein (LDL) through non-saturable pathways produced the same fall in 3-hydroxy-3-methylglutaryl-CoA reductase activity as receptor-mediated degradation of acetylated LDL, yet did not lead to as great an increase in incorporation of [14C]oleate into cholesteryl esters. Studies using FH cells showed that the simultaneous addition of LDL did not reduce oleate incorporation resulting from degradation of acetylated LDL, and that there was a similar relationship for both lipoproteins between the increase in net oleate incorporation and the increase in the cholesteryl ester content of the cells. FH cells maintained in serum-free medium accumulated more free cholesterol than cells in lipoprotein-deficient serum when incubated with LDL but not when incubated with acetylated LDL. The results suggest that the cholesterol released from non-saturable degradation of LDL is more easily removed from the cells by acceptors in the medium than cholesterol released from receptor-mediated uptake of acetylated LDL, and is not readily available for esterification.
Cholesterol Esters↗
Prognosis in breast carcinoma utilizing plasma carcinoembryonic antigen and histologic characteristics of the primary tumor.
Plasma carcinoembryonic antigen (CEA) concentrations in 128 patients with breast cancer were measured preoperatively. The data were related to the histologic features of the primary breast carcinoma and to the clinical follow-up data. Analysis of the plasma CEA values did not show a significant correlation with the histologic type and the histologic and nuclear grade of the primary tumor (n = 73) as well as to the presence or absence of keratin, necrosis, desmoplasia, tubule formation and mucin production. Furthermore, the results indicated that high CEA values (more than 10 ng/ml) may be associated with distant metastasis and not with the metastatic spread to lymph nodes. High CEA levels were also associated with reduced survival of the patients. This study confirms our previous report suggesting that high CEA levels are correlated with tumors of endodermal origin, whereas the CEA levels were within the normal range in the tumors of ectodermal origin. In agreement with other studies, however, it was found that the predictive value of plasma CEA concentrations in general is weak, so that the use of CEA measurement for prognosis is of limited value.
Breast Neoplasms↗