Biomedical subjects

H O Smith

Publications and source records attributed to H O Smith.

At least 37 records · Page 2Linked to original sources

PubMed1998

The malaria genome sequencing project.

An international consortium of genome centres, advanced development teams and funding agencies has begun the task of sequencing the genome of the parasite Plasmodium falciparum, the most important cause of human malaria. Sequencing is proceeding chromosome by chromosome, and the annotated sequence of chromosome 2 is nearly finished. With the continual release of sequence data as they are generated, malaria researchers have access to a steady stream of genomic sequences and will soon have the complete annotation of all of the estimated 5000-7000 P. falciparum genes. The task will then be how to best apply these data to the development of new anti-malarial drugs, vaccines and diagnostic tests. This review provides a brief overview of the Malaria Genome Sequencing Project and suggests potential directions for future malaria research.

Journal Article↗

PubMed1998

Sequencing the genome of Plasmodium falciparum.

Advances in microbial genomic sequencing have the potential to revolutionize the control of infectious diseases. Recently, a consortium of researchers and funding agencies from the United States and Great Britain have embarked on a project to sequence the genome from Plasmodium falciparum, the most important cause of human malaria. The Malaria Genome Sequencing Project has reached an important milestone with the completion of the entire DNA sequence and annotation of chromosome 2, a 950 kilobase chromosome of Plasmodium falciparum. This review article will provide an overview of the malaria genome sequencing project, highlight progress in the field of microbial sequencing, and suggest new directions for future malaria research.

Journal Article↗

PubMed1998

A new transformation-deficient mutant of Haemophilus influenzae Rd with normal DNA uptake.

Haemophilus influenzae Rd is a gram-negative natural transformer. A mutant strain, RJ248, that has normal DNA uptake and translocation but whose transformation frequency is 300 times lower than that of wild-type H. influenzae and whose phage recombination is 8 times lower was isolated. The affected gene, comM, is induced during competence development in wild-type H. influenzae but not in RJ248.

DNA Transposable Elements↗

PubMed1997

Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi.

The genome of the bacterium Borrelia burgdorferi B31, the aetiologic agent of Lyme disease, contains a linear chromosome of 910,725 base pairs and at least 17 linear and circular plasmids with a combined size of more than 533,000 base pairs. The chromosome contains 853 genes encoding a basic set of proteins for DNA replication, transcription, translation, solute transport and energy metabolism, but, like Mycoplasma genitalium, it contains no genes for cellular biosynthetic reactions. Because B. burgdorferi and M. genitalium are distantly related eubacteria, we suggest that their limited metabolic capacities reflect convergent evolution by gene loss from more metabolically competent progenitors. Of 430 genes on 11 plasmids, most have no known biological function; 39% of plasmid genes are paralogues that form 47 gene families. The biological significance of the multiple plasmid-encoded genes is not clear, although they may be involved in antigenic variation or immune evasion.

Biological Transport↗

PubMed1997

The complete genome sequence of the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus.

Archaeoglobus fulgidus is the first sulphur-metabolizing organism to have its genome sequence determined. Its genome of 2,178,400 base pairs contains 2,436 open reading frames (ORFs). The information processing systems and the biosynthetic pathways for essential components (nucleotides, amino acids and cofactors) have extensive correlation with their counterparts in the archaeon Methanococcus jannaschii. The genomes of these two Archaea indicate dramatic differences in the way these organisms sense their environment, perform regulatory and transport functions, and gain energy. In contrast to M. jannaschii, A. fulgidus has fewer restriction-modification systems, and none of its genes appears to contain inteins. A quarter (651 ORFs) of the A. fulgidus genome encodes functionally uncharacterized yet conserved proteins, two-thirds of which are shared with M. jannaschii (428 ORFs). Another quarter of the genome encodes new proteins indicating substantial archaeal gene diversity.

Archaeoglobus fulgidus↗

PubMed1997

The complete genome sequence of the gastric pathogen Helicobacter pylori.

Helicobacter pylori, strain 26695, has a circular genome of 1,667,867 base pairs and 1,590 predicted coding sequences. Sequence analysis indicates that H. pylori has well-developed systems for motility, for scavenging iron, and for DNA restriction and modification. Many putative adhesins, lipoproteins and other outer membrane proteins were identified, underscoring the potential complexity of host-pathogen interaction. Based on the large number of sequence-related genes encoding outer membrane proteins and the presence of homopolymeric tracts and dinucleotide repeats in coding sequences, H. pylori, like several other mucosal pathogens, probably uses recombination and slipped-strand mispairing within repeats as mechanisms for antigenic variation and adaptive evolution. Consistent with its restricted niche, H. pylori has a few regulatory networks, and a limited metabolic repertoire and biosynthetic capacity. Its survival in acid conditions depends, in part, on its ability to establish a positive inside-membrane potential in low pH.

Antigenic Variation↗

PubMed1997

In vitro Tn7 mutagenesis of Haemophilus influenzae Rd and characterization of the role of atpA in transformation.

Haemophilus influenzae Rd is a gram-negative bacterium capable of natural DNA transformation. The competent state occurs naturally in late exponential growth or can be induced by a nutritional downshift or by transient anaerobiosis. The genes cya, crp, topA, and sxy (tfoX) are known to function in the regulation of competence development. The phosphoenolpyruvate:carbohydrate phosphotransferase system functions to maintain levels of cyclic AMP necessary for competence development but is not directly involved in regulation. The exact signal(s) for competence and the genes that mediate the signal(s) are still unknown. In an effort to find additional regulatory genes, H. influenzae Rd was mutated by using an in vitro Tn7 system and screened for mutants with a reduced ability to induce the competence-regulatory gene, comA. Insertions in atpA, a gene coding for the alpha subunit of the F1 cytoplasmic domain of the ATP synthase, reduce transformation frequencies about 20-fold and cause a significant reduction in expression of competence-regulatory genes, while the expression of constitutive competence genes is only minimally affected. In addition, we found that an insertion in atpB, which encodes the a subunit of the F0 membrane-spanning domain, has a similar effect on transformation frequencies.

Bacterial Proteins↗

PubMed1996

A new strategy for genome sequencing.

Existing approaches to sequencing the human genome are based on the assumption that each region to be sequenced must first be mapped. But there is a simpler strategy in which any number of laboratories can cooperate.

Animals↗

PubMed1996

Endodermal sinus tumor and embryonal carcinoma of the ovary in a 53-year-old woman.

BACKGROUND: Germ cell tumors, the most common ovarian malignancies in females under the age of 21, are rare in older women. We report an unusual case of a mixed embryonal carcinoma and endodermal sinus germ cell tumor in a perimenopausal patient and review the differential diagnosis and management of these malignancies with respect to age. CASE: A 53-year-old woman complaining of irregular menses and pelvic pain was found to have a large pelvic mass and a positive pregnancy test. Subsequent investigation revealed a large left adnexal mass, and an elevated beta-HCG and alpha-AFP. At laparotomy, a mixed germ cell tumor was found. The patient was treated with multiagent chemotherapy and currently is without evidence of disease. CONCLUSION: Although rare, the diagnosis of germ cell tumor should be considered in older women presenting with a large pelvic mass. The treatment and prognosis is similar regardless of age, except that reproductive-sparing surgery is not a priority in the older patient.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Role of the two-component signal transduction and the phosphoenolpyruvate: carbohydrate phosphotransferase systems in competence development of Haemophilus influenzae Rd.

Haemophilus influenzae Rd becomes competent for transformation by nutritional downshift or transient anaerobic growth through a process that requires cyclic AMP receptor protein and adenylate cyclase. Insertion mutations in crr or ptsI of the phosphoenolpyruvate:carbohydrate phosphotransferase system lowered transformation frequencies, and the effect was reversed by the addition of cyclic AMP. However, insertions into H. influenzae homologs of two-component signal transduction genes had no effect on competence.

Haemophilus influenzae↗

PubMed1996

Laparoscopic surgery in patients with a ventriculoperitoneal shunt. A case report.

BACKGROUND: Ventriculoperitoneal shunts have afforded many patients the opportunity to expect a normal lifespan. Since laparotomy is more likely to be associated with adhesion formation, potentially reducing the functional capacity of ventriculoperitoneal shunts, laparoscopy may be a preferable surgical alternative. CASE: A 64-year-old woman presented with a pelvic mass requiring surgical evaluation to rule out ovarian cancer. She had a ventriculoperitoneal shunt. Diagnostic laparoscopy was performed without complication. However, due to the significant adhesions from previous surgery, the mass could not be safely evaluated, and the procedure was completed by laparotomy. CONCLUSION: This is the first report of laparoscopy for a pelvic mass in an adult with a ventriculoperitoneal shunt. Laparoscopy is preferable to laparotomy for the replacement or repair of ventriculoperitoneal shunts. Also, laparoscopy should be considered for other problems requiring surgical intervention.

Female↗

PubMed1996

Ovarian cancer incidence and mortality in American Indian, Hispanic, and non-Hispanic white women in New Mexico.

Although ethnic and racial differences in ovarian cancer incidence and mortality have been reported worldwide, few published data have addressed the epidemiology of ovarian cancer among U.S. American Indians and Hispanics. We reviewed ovarian cancer incidence and survival data from New Mexico's population-based cancer registry collected from 1969 to 1992, and examined state vital records data for ovarian cancer deaths collected from 1958 to 1992, focusing on ethnic differences in occurrence and outcomes of ovarian malignancies. Non-Hispanic white women had age-adjusted incidence rates that were slightly higher (13.3/100,000) than rates for American Indians (11.4) and Hispanics (10.7) over the 24-year period. Ovarian cancer mortality rates were also higher for non-Hispanic whites than for minority women. Neither incidence rates nor mortality rates for ovarian cancer improved over the span of the study period. In addition, the stage at diagnosis did not shift substantially over time for any of the ethnic groups studied, nor did the distribution of various histopathological types shift proportionately. Only slight improvement was observed in 5-year survival over the time period of the study, with greater gains among younger (50 years old or less) versus older women. Ethnic differences in ovarian cancer incidence and mortality were apparent in our population-based data. However, our analysis indicated no reduction in ovarian cancer incidence or mortality in our state over the past quarter century and only slight improvement in 5-year survival.

Adenocarcinoma↗

PubMed1995

The minimal gene complement of Mycoplasma genitalium.

The complete nucleotide sequence (580,070 base pairs) of the Mycoplasma genitalium genome, the smallest known genome of any free-living organism, has been determined by whole-genome random sequencing and assembly. A total of only 470 predicted coding regions were identified that include genes required for DNA replication, transcription and translation, DNA repair, cellular transport, and energy metabolism. Comparison of this genome to that of Haemophilus influenzae suggests that differences in genome content are reflected as profound differences in physiology and metabolic capacity between these two organisms.

Antigenic Variation↗

PubMed1995

Frequency and distribution of DNA uptake signal sequences in the Haemophilus influenzae Rd genome.

The naturally transformable, Gram-negative bacterium Haemophilus influenzae Rd preferentially takes up DNA of its own species by recognizing a 9-base pair sequence, 5'-AAGTGCGGT, carried in multiple copies in its chromosome. With the availability of the complete genome sequence, 1465 copies of the 9-base pair uptake site have been identified. Alignment of these sites unexpectedly reveals an extended consensus region of 29 base pairs containing the core 9-base pair region and two downstream 6-base pair A/T-rich regions, each spaced about one helix turn apart. Seventeen percent of the sites are in inverted repeat pairs, many of which are located downstream to gene termini and are capable of forming stem-loop structures in messenger RNA that might function as signals for transcription termination.

Base Composition↗

PubMed1995

A prospective randomized comparison of an attached silver-impregnated cuff to prevent central venous catheter-associated infection.

The VitaCuff catheter, a specialized central venous catheter (CVC) with an attached silver-impregnated cuff, is designed to permit percutaneous placement and prolonged venous access. A prospective randomized study was undertaken comparing the VitaCuff with standard triple lumen catheters to determine if the VitaCuff reduces infection during extended use. All consenting patients underwent percutaneous placement of subclavian lines. By study design, control and VitaCuff catheters could remain in site for up to 7 and 14 days, respectively. Cultures were obtained from the preinsertion skin site, and upon removal, from the skin, hubs, infusates, CVC tip, and cuff. Statistical methods included chi 2, the Student t test, and the log-rank test on Kaplan-Meier estimates. Of 133 patients completing this study, 64 patients (48.1%) underwent VitaCuff placement and 69 patients (51.8%) served as controls. In 124 patients (93.2%), the indication for catheter placement was for perioperative care. Overall, 67 patients (50.4%) required central venous access > 7 days, necessitating > or = 1 additional line in 29 patients (21.8%). The incidence of pneumothorax per patient from the initial central line insertion was 4/104 (3.85%), significantly lower than the 4/29 (13.8%) incidence during secondary catheter placement (P = 0.046). Culture results upon catheter removal demonstrated a reduction in colonization of skin sites and hubs for the VitaCuff patients, but not for catheter tips or infusates. Regardless of the type of catheter used, colonization was dependent upon duration of insertion. The incidence of catheter-related sepsis was 6.8%, and did not differ significantly between the study groups. Multiple CVC insertions increase the incidence of pneumothorax. Because VitaCuff catheters permit extended access up to 14 days without increasing the incidence of sepsis, we recommend their use in patients who require prolonged CVC access.

Catheterization, Central Venous↗

PubMed1995

Cutaneous metastases from squamous cell carcinoma of the vulva. A case report and review of the literature.

Cancer of the vulva, the fourth most common malignancy of the female genital tract, accounts for approximately 4% of all gynecologic malignancies. Only one prior case of a cutaneous metastasis from a vulvar cancer has been previously reported and involved a FIGO Stage III (T2N1M0) lesion. We report a patient with Stage II (T2N0M0) vulvar carcinoma who developed cutaneous metastases. This case demonstrates the ability of vulvar carcinoma to disseminate hematogenously, despite complete surgical resection with negative skin margins, and negative lymph nodes. In addition, this case emphasizes the importance of careful and close follow-up of all patients with vulvar carcinoma.

Carcinoma, Squamous Cell↗

PubMed1995

The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma.

Colony-stimulating factor 1 (CSF-1) is a homodimeric growth factor that humorally regulates the growth and differentiation of mononuclear phagocytes, and locally regulates maternal-fetal interactions during pregnancy. It exerts these actions through a transmembrane tyrosine kinase receptor, colony-stimulating factor 1 receptor (CSF-1R), the product of the c-fms proto-oncogene. Recent studies have demonstrated overexpression of CSF-1 and its receptor in breast, ovarian, and endometrial adenocarcinomas. To further investigate the possible role of CSF-1 and its receptor in the pathogenesis of endometrial adenocarcinoma, a prospective study was undertaken to study CSF-1 expression in benign and neoplastic endometrial epithelium and to compare serum CSF-1 levels in endometrial adenocarcinoma patients with healthy perimenopausal women. The mean serum levels of CSF-1 in 71 patients with endometrial cancer (4.9 +/- 1.8 microgram/liter) were significantly elevated compared with levels found in the 32 controls (3.5 +/- 1.1 microgram/liter). Within the endometrial adenocarcinoma group, circulating CSF-1 levels were significantly elevated in patients with large tumor volume, high grade, myometrial invasion, residual disease, and circulating CA-125 levels. High serum levels of serum CSF-1 were associated with elevated serum CA19-9 and CA-125 levels. Immunohistochemistry results revealed in tumor epithelium intense staining for CSF-1R (27 of 54 cases, 50%) and elevated staining for CSF-1 (41 of 54 cases, 75.9%), with intense staining of CSF-1 in 16 of 54 cases (29.6%). Staining was significantly greater in intensity and number of cells involved in malignant compared with benign epithelium for CSF-1R and CSF-1 (P = 0.05 and <0.0001, respectively). A positive correlation between amount and intensity of CSF-1 and CSF-1R staining in endometrial adenocarcinoma tissue was also demonstrated (P = 0.007). CSF-1 and CSF-1R mRNA was also detected in the tumor samples, confirming the expression of the protein in these tissues. Reverse transcription-PCR demonstrated the presence of mRNA for both the transmembrane and secreted forms of CSF-1 in all tumors analyzed. These results therefore support the hypotheses that CSF-1 and CSF-1R are overexpressed in endometrial adenocarcinoma, that levels of expression significantly correlate with clinicopathological risk factors for poor outcome, and that CSF-1 in association with its receptor via autocrine, juxtacrine, and/or paracrine interactions has a causal role in endometrial adenocarcinoma development and proliferation.

Adenocarcinoma↗

PubMed1994

Distinctive flow histogram pattern in molar pregnancies with elevated maternal serum human chorionic gonadotropin levels.

BACKGROUND: Flow cytometric analysis of trophoblastic tissue has shown that most partial hydatidiform moles (PMs) are triploid, whereas most complete moles (CMs) are diploid or tetraploid. Ploidy analysis can support a diagnosis of CM or PM. However, in some cases, a precise diagnosis cannot be rendered. METHODS: This study examined DNA flow histograms in 86 cases of histologically diagnosed moles and nonmoles to identify patterns specific to moles to eliminate indeterminate diagnoses. Forty hydropic abortions, 17 CMs, and 29 PMs were analyzed, and results were correlated with microscopic appearance and maternal serum human chorionic gonadotropin (HCG) levels. RESULTS: Analysis of nondiploid histologic moles in which the initial maternal serum HCG level was greater than 150,000 mIU/ml showed similar histograms in 12 of 14 cases. In these 12 specimens, a distinct aneuploid peak could not be delineated from multiple cell populations between the G0/G1 and G2/M or G0/G1diploid and G0/G1aneuploid peaks. This commonly appeared as a slope rising toward the tetraploid region. S-phase fraction values showed a trend toward higher values in the moles versus nonmoles, but the difference was not statistically significant. CONCLUSIONS: This sloping histogram pattern may reflect progression from a single aneuploid to multiple aneuploid populations. Its statistically significant correlation (P < 0.001) with high maternal serum HCG values suggests the presence of a highly metabolically active population of aneuploid trophoblast. Because it appears specific to nondiploid moles, recognition of the pattern will aid in the distinction of mole from hydropic spontaneous abortion.

Abortion, Spontaneous↗