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D H Smith

Publications and source records attributed to D H Smith.

At least 253 records · Page 14Linked to original sources
PubMed1985

Evaluation of complement fixation procedures for the diagnosis of visceral leishmaniasis.

Three complement fixation (CF) procedures were evaluated for their ability to detect serum antibodies to visceral leishmaniasis. These tests differ in their use of buffers, volumes of complement and sensitized erythrocyte concentrations, incubation times and percentage haemolysis endpoints. Freeze-thawed sonicates of Leishmania donovani promastignotes were used as antigen. Test sensitivity was determined using sera from 46 Kenyans with parasitologically proven leishmaniasis. The frequencies of positive reactions in all three tests were 96-97% and positive antibody titres ranged from 1:16 to 1:4096. Specificity was determined with 20 sera from healthy individuals with no known exposure to leishmaniasis. The frequencies of false positive reactions were 0-10% in the control sera, with titres up to 1:16. No cross-reactions were observed with sera from patients with bacterial, fungal and other parasitic diseases. In replicate experiments, 99-100% of the sera tested were within one titre dilution of each other. All three CF procedures provide very good sensitivity, specificity and low cross-reactivity and are statistically similar in their capacity to diagnose visceral leishmaniasis.

Adolescent↗
PubMed1985

Design of anticancer drugs using modeling techniques.

Flexibility of intercalation site geometries within a B-DNA helix was investigated in the twist-shift plane using energy minimization methods. The parameters optimized included sugar conformation, the glycosidic angles and phosphodiester torsion angles. Our calculations show several regions of energetically favorable intercalation geometries in the twist-shift plane. Modeling studies using interactive computer graphics and electrostatic potential surface compatibility provided initial hypotheses for the structures of the drug-DNA complexes. These hypotheses were supported and extended by energy minimizations of these complexes. Binding positions, conformational features and relative minimum binding energies of two anticancer drugs, mitoxantrone and bisantrene, were computed for intercalation complexes with DNA in the theoretically defined intercalation sites. Mitoxantrone intercalates DNA from the minor groove and the side chain OH or NH groups are involved in hydrogen bonds with the main chain phosphate groups of DNA, thereby cross-linking the complementary strands. The hydroxyl groups of mitoxantrone can also participate in hydrogen bonding with phosphate oxygens of another chain, thereby cross-linking DNA helices. Bisantrene intercalates DNA favorably from the major groove and the NH group of the dihydroimidazole ring can participate in hydrogen bonding with the phosphate oxygens of the backbone. These models are consistent with the physicochemical and electron microscopic studies of the interaction of mitoxantrone and bisantrene with DNA. Our results are now being used to guide the design of novel anticancer drugs that should interact with DNA in a manner similar to that proposed for our representative drugs.

Anthracenes↗
PubMed1985

Vector expression of adenovirus type 5 E1a proteins: evidence for E1a autoregulation.

We transiently expressed adenovirus type C E1a proteins in wild-type or mutant form from plasmid vectors which have different combinations of E1a and simian virus 40 enhancer elements and which contain the DNA replication origin of SV40 and can replicate in COS 7 cells. We measured the levels of E1a mRNA encoded by the vectors and the transition regulation properties of the protein products. Three vectors encoded equivalent levels of E1a mRNA in COS 7 cells: (i) a plasmid encoding the wt 289-amino acid E1a protein (this complemented the E1a deletion mutant dl312 for early region E2a expression under both replicative and nonreplicative conditions); (ii) a vector for the wt 243-amino acid E1a protein (this complemented dl312 weakly and only under conditions of high multiplicities of dl312); (iii) a mutant, pSVXL105, in which amino acid residues-38 through 44 of the 289-amino acid E1a protein (which includes two highly conserved residues) are replaced by 3 novel amino acids (this also complemented dl312 efficiently). A fourth vector, mutant pSVXL3 with which linker substitution shifts the reading frame to encode a truncated 70-amino acid fragment from the amino terminus of the 289-amino acid protein, was unable to complement dl312. Surprisingly, pSVXL3 overexpressed E1a mRNA approximately 30-fold in COS 7 cells in comparison with the other vectors. The pSVXL3 overexpression could be reversed by cotransfection with a wt E1a vector. We suggest that wt E1a proteins regulate the levels of their own mRNAs through the recently described transcription repression functions of the 289- and 243-amino acid E1a protein products and that pSVXL3 fails to autoregulate negatively.

Adenovirus Early Proteins↗
PubMed1985

A pilot study of adjuvant therapy in patients with cervical cancer at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy.

The prognosis after surgical therapy (radical hysterectomy and pelvic lymphadenectomy) of stages IB and IIA carcinoma of the cervix is affected by several histopathologic findings within the resected specimen. Patients at high risk of recurrence include those with involved pelvic lymph nodes, lymphatic or vascular invasion in the cervix, tumor size greater than 4 cm, grade 3 lesions, adenosquamous histology, parametrial invasion, and evidence of locally metastatic (noncontiguous) disease. We report the results of adjuvant chemotherapy (cisplatin and bleomycin) and pelvic radiotherapy in 32 patients with cervix cancer deemed to be at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy. The continuous disease-free survival rate for the 32 evaluable patients in 84% at a mean and median follow-up time of 28 months. Three patients are dead of disease and two patients are alive after treatment of local recurrences giving a survival rate of 91%. The two patients who are alive after disease recurrence demonstrated only locally recurrent disease while the three patients who have died with recurrent disease relapsed both locally and systemically. Complications of this treatment program were not significantly greater than those observed in prior studies using the combination of surgery and adjuvant radiotherapy without chemotherapy. When compared with the results from historical controls in a large series of similar patients at the same institution, the results in this pilot study are encouraging and would seem to justify a randomized prospective clinical trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Cloning, nucleotide sequence, and expression in Escherichia coli of the exotoxin A structural gene of Pseudomonas aeruginosa.

A 2760-base pair DNA segment of the Pseudomonas aeruginosa strain PA103 chromosome encoding the exotoxin A (ETA) structural gene has been cloned in Escherichia coli and the nucleotide sequence has been determined. Analysis of the 5'- and 3'-flanking regions indicate that ETA is translated from a monocistronic message. Comparison of the deduced NH2-terminal amino acid sequence with that determined by sequence analysis of the secreted protein indicates that ETA is made as a 638 amino acid precursor from which a highly hydrophobic leader peptide of 25 amino acids is removed during the secretion process. Data are presented that indicate a COOH-terminal location of the ADP-ribosylation activity of the molecule. Expression of the ETA coding sequence in E. coli under control of the E. coli trp promoter, but not the ETA promoter, results in the production of enzymatically and immunologically active protein. However, most of this material appears to be neither processed nor secreted. Comparison of the ETA amino acid and nucleotide sequences to those of diphtheria toxin revealed no significant homologies, indicating that these functionally similar toxins evolved from different genes.

ADP Ribose Transferases↗
PubMed1984

A complement fixation test for visceral leishmaniasis using homologous parasite antigen I.

The complement fixation test using homologous parasite antigen was evaluated in 60 individuals with confirmed visceral leishmaniasis and compared with the results obtained in individuals with other parasitic and infectious diseases; 88% of the confirmed cases of visceral leishmaniasis were positive whilst no positive reactions were observed in individuals with other infectious and parasitic diseases. The specificity was partially compromised by anticomplementary activity in 5%, limited to individuals with visceral leishmaniasis, and doubtful (2%) or sero-negative (7%) results.

Antigens, Protozoan↗
PubMed1984

A complement fixation test for visceral leishmaniasis using homologous parasite antigen II. Results in an endemic area in Kenya.

Further studies of the complement fixation test using homologous parasite antigen in an endemic area for visceral leishmaniasis have showed that 82% of individuals with proven visceral leishmaniasis were positive initially whilst 92% were positive at some stage during their illness. Titres fell slowly following effective treatment and anticomplementary activity, confined to confirmed visceral leishmaniasis, was usually lost during treatment. Individuals with alternative causes of hepatosplenomegaly from the same population were negative apart from those with a presumptive diagnosis of visceral leishmaniasis but without parasitological confirmation. Less than 1% of people in the same endemic area without visceral leishmaniasis were positive, suggesting that preliminary serodiagnostic investigation would limit the need for invasive investigation under field conditions.

Adolescent↗
PubMed1984

Haematuria occurring during antirheumatoid therapy.

One hundred and ninety-one patients treated with gold and penicillamine over a seven-year period were reviewed retrospectively for the occurrence of haematuria. Over this period 10% had shown haematuria, and in over half of these an identifiable cause was found. In the remaining patients, a clear relationship with their treatment seemed likely in only two. Penicillamine therapy was discontinued in all patients with unexplained haematuria, but two patients have continued to show haematuria. Gold therapy has been continued in the presence of haematuria without ill effect. There has been no deterioration in renal function in those patients who have continued to show unexplained haematuria and at no time was proteinuria an accompanying feature.

Adult↗
PubMed1984

Cloning and sequencing of the xylose isomerase and xylulose kinase genes of Escherichia coli.

A 4.2-kilobase-pair fragment of the Escherichia coli chromosome which contains the genes for xylose isomerase and xylulose kinase was cloned into plasmid pBR322. The hybrid plasmid (designated pECX14) complements strains deficient in either or both of the two enzymes. Deletion derivatives of pECX14 were used to localize the two genes on the cloned fragment. The entire nucleotide sequence of the cloned fragment was determined. Open reading frames which, if translated, would encode proteins of molecular weights 54,000 and 52,000 were found. These were identified as the isomerase and kinase structural genes, respectively.

Aldose-Ketose Isomerases↗
PubMed1984

Enteric fistulas encountered on a gynecologic oncology service from 1969 through 1980.

In the 12 year period from 1969 to 1980, 56 patients with a total of 68 enteric fistulas were seen at the Gynecology Service of the Memorial Sloan-Kettering Cancer Center. Prior therapy was common, with 98 per cent of the patients having had previous surgical treatment and 88 per cent of the patients had had prior surgical treatment and radiation therapy. Management consisted of three phases: stabilization, definition and surgical therapy. Of the surgically treated patients, 89 per cent had successful fistula closure. Although TPN as a primary therapy was unsuccessful, adequate nutrition was essential in the management of these patients. In our series, surgical care was the final step in successful management. Of the possible types of operation, those providing total exclusion of the fistula from the intestinal stream proved to be most effective.

Colectomy↗
PubMed1983

Identification and nucleotide sequence of a human locus homologous to the v-myc oncogene of avian myelocytomatosis virus MC29.

Avian myelocytomatosis virus MC29 is a replication-defective acute leukaemia virus which induces a variety of tumours in chickens including sarcomas, renal and hepatic carcinomas, and myelocytomatosis. The oncogenic potential of the virus is mediated by the gene v-myc, acquired from sequences (c-myc) present in normal uninfected chicken DNA. Sequences closely related to chicken c-myc have been highly conserved throughout evolution, from Drosophila to vertebrates. The hypothesis that c-myc may be involved in neoplastic transformation has been strengthened by the finding that B-cell lymphomas induced in chickens by avian leukosis virus (ALV) are often associated with increased expression of c-myc resulting from integration of the ALV provirus adjacent to the c-myc gene. More recently, it has been demonstrated that the malignant human cell line HL-60, derived from the peripheral blood leukocytes of a patient with acute promyelocytic leukaemia, expresses elevated levels of myc-related mRNA associated with an amplification of the c-myc gene. To explore the relationship of the human cellular myc gene with the corresponding viral oncogene from MC29, and to provide a framework for the analysis of the mechanism and significance of c-myc amplification in human tumours, we have isolated and determined the nucleotide sequence of a genomic clone prepared from a normal human library which contains all domains sharing homology with v-myc.

Amino Acid Sequence↗
PubMed1983

Ultrasonic signs of imminent ovulation.

Two consistent signs of imminent ovulation in the Graafian follicle have been identified using ultrasound. These signs are a line of decreased reflectivity around the follicle and a crenation pattern within the follicle. The signs may be useful in programs such as in vitro fertilization and artificial insemination, in which timing of ovulation is critical.

Female↗
PubMed1983

The prediction of pregnancy failure by measurement of pregnancy-associated plasma protein A (PAPP-A) following in vitro fertilization and embryo transfer.

Circulating PAPP-A was measured serially in five patients following successful IVF-ET. PAPP-A concentrations were consistently normal in all three patients in whom pregnancies progressed normally to term. Depressed levels of PAPP-A were observed in one patient who miscarried spontaneously at 17 weeks' gestation despite ultrasound evidence of normal fetal development. Circulating PAPP-A was not detected in the fifth patient, whose tubal pregnancy ruptured at 8 weeks. These data are discussed in relation to surveillance of pregnancies following IVF-ET.

Abortion, Spontaneous↗
PubMed1983

Nucleotide sequence to the v-myc oncogene of avian retrovirus MC29.

Avian myelocytomatosis viruses are retroviruses whose oncogene (v-myc) induces an unusually wide variety of tumors, including carcinomas, endotheliomas, sarcomas, and myelocytomatoses. The viral gene v-myc arose by transduction of an undetermined portion of a cellular gene known as c-myc. In order to facilitate further studies of the functions of v-myc and c-myc and to permit detailed comparisons between the two genes, we have determined the nucleotide sequence of v-myc in the genome of the MC29 strain of myelocytomatosis virus. The v-myc domain in MC29 virus encodes a hydrophilic polypeptide with a molecular weight of 47,000, fused to a portion of the polyprotein encoded by the viral structural gene gag. The carboxyl-terminal half of the v-myc polypeptide is rich in basic amino acid residues. This feature may account for the DNA-binding properties of the hybrid gag-myc-encoded protein which would have a molecular weight of approximately 100,000, in accord with results from previous studies of the protein encoded by v-myc. The junctions between v-myc and the genome of the transducing virus are apparent but reveal no clues to the mechanism by which transduction might occur.

Amino Acid Sequence↗