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Biomedical subjects

G R Smith

Publications and source records attributed to G R Smith.

At least 109 records · Page 6Linked to original sources
PubMed1996

Renal failure in Wilms' tumor patients: a report from the National Wilms' Tumor Study Group.

This report defines the incidence and determines the etiology of renal failure (RF) in patients undergoing treatment for Wilms' tumor (WT). The database of the National Wilms' Tumor Study (NWTS) was searched to identify all children reported to have developed chronic renal failure. There were 55 patients found to have RF. Of these, 39 patients had bilateral tumors, 15 with unilateral disease and one with a WT in a solitary kidney. The median interval from diagnosis to the onset of renal failure was 21 months. The incidence of RF in bilateral WT was 16.4% for NWTS-1 & -2, 9.9% for NWTS-3, and 3.8% for NWTS-4. The incidence of RF in unilateral WT remained stable. The most common etiologies of RF were: bilateral nephrectomy for persistent or recurrent tumor (24 pts), Drash syndrome (12 pts), progressive tumor in the remaining kidney (5 pts), radiation nephritis (6 pts), and other causes (5 pts). The etiology of renal failure was not reported in three children. Children with unilateral WT and a normal contralateral kidney have a very low incidence of RF, and this review does not support a recommendation for parenchymal sparing procedures in these patients. Children with bilateral WT are at risk for the development of RF, and parenchymal sparing procedures are warranted.

Child↗
PubMed1996

Sequence diversity in the NIb coding region of eight sugarcane mosaic potyvirus isolates infecting sugarcane in Australia.

We have sequenced the NIb coding region of sugarcane mosaic potyvirus strain SC (SCMV-SC) and eight field isolates of SCMV from Australia. This region comprised 1563 nucleotides and encoded a putative protein of 521 amino acids containing the consensus motif GDD. The protease cleavage sites between the NIa/NIb and the NIb/coat protein were found to be Q/C and Q/A, respectively. The SCMV sequences were most similar to sorghum mosaic potyvirus with identities of 70% and 78% at the nucleotide and amino acid levels, respectively. When the sequences were compared to each other, there was a maximum of 3.3% variation between isolates at the nucleotide level and a maximum of 0.8% at the amino acid level. Phylogenetic analysis of the sequences indicated the field isolates were grouped according to their geographical location. The SCMV sequence with most homology to all other isolates has been selected to generate constructs for replicase-mediated resistance.

Amino Acid Sequence↗
PubMed1996

Requirement of S. pombe exonuclease II, a homologue of S. cerevisiae Sep1, for normal mitotic growth and viability.

Exonuclease II (ExoII) from Schizosaccharomyces pombe is a 5'-->3' single-stranded DNA exonuclease. We have cloned its gene, exo2, whose nucleotide sequence revealed that ExoII is a homologue of the multifunctional Saccharomyces cerevisiae Sep1 protein (also called Kem1, Xrn1, Rar5, Dst2). S. pombe exo2 null mutants were cold-sensitive for growth, had increased cell size at the restrictive temperature, were hypersensitive to the mitotic inhibitor thiabendazol and to caffeine, and died rapidly in stationary phase. Many of these phenotypes are similar to those of sep1 (kem1 or xrn1) mutants of S. cerevisiae. In contrast, the exo2 mutation had only a moderate effect on progression through meiosis and no significant effect on meiotic recombination. We discuss possible functions of the multifunctional ExoII protein.

Amino Acid Sequence↗
PubMed1996

Oral vaccination against pseudotuberculosis.

Yersinia pseudotuberculosis strain M5 (serogroup IA), isolated from the faeces of a mara, was of considerable virulence for mice by intravenous inoculation, but of low virulence by oral administration, almost always producing no more than a transient infection, mainly of the mesenteric lymph nodes. Oral infection of mice with strain M5, either with a single dose of culture per os or by the administration of dilute culture in drinking water, protected strikingly against the illness and death normally produced by oral infection with virulent strains. Lesions of pseudotuberculosis frequently developed in vaccinated mice as a result of challenge, but such lesions often became sterile. Strain M5 gave protection against four heterologous strains (two serogroup IA, two serogroup IB). These results are of interest in relation to the possible immunization of (1) feral animals, living free in the wild or in animal reserves, and (2) some captive wild species in zoological collections or laboratories.

Administration, Oral↗
PubMed1996

Renal salvage procedures in patients with synchronous bilateral Wilms' tumors: a report from the National Wilms' Tumor Study Group.

Synchronous bilateral Wilms' tumor accounts for 4% to 6% of all Wilms' tumors. Renal salvage procedures (partial nephrectomy and enucleation) have been recommended to conserve renal parenchyma. The objective of this study was to review the results of renal salvage operations performed in children who had bilateral neoplasms. The authors reviewed the records of 98 children enrolled in the Fourth National Wilms' Tumor Study who had synchronous bilateral tumors and underwent renal salvage procedures. One hundred thirty-four kidneys were managed with renal salvage procedures. Complete excision of gross disease was accomplished in 118 (88%) of the 134 kidneys. Local tumor recurrence in the remnant kidney or tumor bed occurred in 11 cases (8.2%). Overall, 72% of the kidneys were preserved, and the 4-year survival rate was 81.7%. The surgical morbidity after a salvage procedure was comparable to that of a complete nephrectomy in patients with unilateral Wilms' tumor. Although the incidence of positive surgical margins is worrisome, it did not invariably lead to local recurrence in the remnant kidney or the tumor bed.

Biopsy↗
PubMed1996

Does this treatment work? Validation of an outcomes module for alcohol dependence.

The purpose of this study was to evaluate the outcomes of routine care administered to alcohol-dependent inpatients. The authors sought to validate a self-administered instrument that measures the types and extent of care delivered, the outcomes of that care, and casemix characteristics that influence the outcomes of care. Seventy-eight patients who were beginning inpatient treatment for alcohol dependence were recruited; 85% were followed 5 months later to examine cross-sectional and longitudinal relationships to gold standard assessments. The self-administered module demonstrated excellent agreement with structured interview assessments of diagnosis (kappa = .81), remission (kappa = .83), and change in severity of alcohol-related problems (r = .66 to .87). Casemix variables, particularly baseline severity, predicted change in alcohol consumption and functional status. The baseline module required 20 minutes for the average patient and 5 minutes for the average clinician to complete, with less than 2% missing data. Results indicated that the module measures key constructs with sufficient precision to assist clinicians and researchers in characterizing the degree to which routine inpatient care for alcohol dependence "works" in their patient population. The entire module is in the public domain and available free of charge to interested users.

Adult↗
PubMed1996

Variation among VA hospitals in length of stay for treatment of depression.

OBJECTIVE: The purpose of the study was to determine the degree of interhospital variation in length of stay for patients treated for depressive disorders in Department of Veterans Affairs (VA) medical centers and to identify the number of hospitals with significantly longer or shorter than average lengths of stay (outlier hospitals). METHODS: The sample included 6,374 veterans discharged from acute psychiatric inpatient units at 107 medical centers in 1992 with a primary diagnosis of major depressive disorder or depressive disorder not otherwise specified. To identify statistical outliers, the average length of stay at each medical center was compared with the overall sample mean while controlling for differences in case mix between hospitals. RESULTS: Patients' demographic characteristics, treatment history, and severity of illness all significantly predicted length of stay at the patient level. After case mix factors were controlled for statistically, approximately 29 percent of the medical centers were found to have mean lengths of stay significantly different (p < .01) from the sample mean. Specifically, 15 percent of the medical centers were short-stay outliers, and 14 percent were long-stay outliers. CONCLUSIONS: Despite the fact that the treatment regimen for depression is relatively standardized and all VA medical centers operate under the same administrative model and reimbursement system, a high degree of interhospital variation was found in treatment duration for depression. Results led to the tentative postulation that variations in treatment duration reflect differences in physicians' practice styles. Substantial opportunities may exist for reducing expenditures for the treatment of depression within the VA health care system.

Adult↗
PubMed1996

Assessment tools in psychiatry.

With the advent of managed care, administrators of mental health care will need to implement outcomes measurement systems that will provide information for cost control and quality improvement. These systems must take into account the changes occurring in the delivery of mental health care, such as the broad range of settings in which mental health care occurs, and allow for the measurement of outcomes over time. A useful system must also be flexible, allowing measures to tailor the system to individual needs. Two types of systems are currently being used. Simple systems measure general outcomes, such as patient satisfaction, at baseline and discharge. More complex systems are disorder-specific and can be used to compare different types of treatments or different groups of patients. The simple systems are less costly but are not as useful to quality improvement. The disorder-specific systems are more expensive, but the information gathered with these systems can be used in quality management. As implementation of these systems becomes more commonplace, challenges such as lack of standardization, patient reluctance to fill out forms, and the need for sensitive measurement instruments will need to be addressed.

Humans↗
PubMed1996

Multiple carpometacarpal dislocations. A case report and review of treatment.

Carpometacarpal dislocations of the ulnar four joints are rare injuries that are usually associated with high-energy trauma. Given the small number of cases reported, there exists some controversy regarding their optimal management. The case of a 27-year-old man who sustained a dorsal dislocation (without associated fractures) of the ulnar four carpometacarpal joints as a result of a fall from a height is presented. The literature regarding these hand injuries is reviewed, and the need for anatomic reduction and stabilization is discussed.

Acetabulum↗
PubMed1995

Monomeric RecBCD enzyme binds and unwinds DNA.

RecBCD enzyme is a multifunctional nuclease that is essential for the major pathway of homologous genetic recombination in Escherichia coli. It has a potent helicase activity that uses ATP hydrolysis to unwind very long stretches of DNA. The functional form of RecBCD enzyme has been unclear, since M(r) of 250,000-655,000 have been previously reported. We have isolated two oligomeric forms of the enzyme, one (monomeric) containing a single copy of the RecB, RecC, and RecD polypeptides, and the other (dimeric) containing two copies of each polypeptide. We show here that the monomeric form of the enzyme (M(r) approximately 330,000) can form a stable initiation complex on the end of ds DNA. Depending on the nature of the ds end, KD estimates ranged from approximately 0.1 nM to approximately 0.7 nM in the presence of Mg2+ ions, which enhanced but was not required for binding. We further showed that the complex of monomeric RecBCD enzyme and a ds DNA end was competent to unwind DNA. A general model for the action of helicases has been proposed that uses repeated conformational changes between two states of a complex between DNA and a dimeric form of the enzyme. Our results make such a model unlikely for RecBCD enzyme.

Base Sequence↗
PubMed1995

Strand specificity of nicking of DNA at Chi sites by RecBCD enzyme. Modulation by ATP and magnesium levels.

RecBCD enzyme is essential for the major pathway of homologous recombination of linear DNA in Escherichia coli. It is a potent nuclease and helicase and, during its unwinding of double-stranded DNA, makes single-strand scissions in the vicinity of Chi recombination hot spots. We report here that both the strand that is cut and the position of the cuts relative to Chi depended on the ATP to Mg2+ ratio. With ATP in excess, Chi-dependent nicks occurred, as we have previously reported, four to six nucleotides to the 3'-side of the Chi octamer (5'-GCTGGTGG-3') and were detected only on the strand bearing that sequence. Three differences were seen with Mg2+ in excess. 1) Chi-dependent 3'-ends were produced on the GCTGGTGG-containing strand closer to and within the Chi octamer. 2) Chi-dependent cuts occurred on the complementary DNA strand. 3) RecBCD enzyme destroyed the 3'-terminated strand of DNA from its entry point up to the vicinity of the Chi site, as others have previously reported. We show here that, with Mg2+ in excess, the enzyme continued to travel along DNA, after encountering a Chi site, releasing both strands of the DNA distal to Chi as single strands. We discuss potential biological consequences of these two modes of RecBCD enzyme-Chi interaction.

Adenosine Triphosphate↗
PubMed1995

A role for exonuclease I from S. pombe in mutation avoidance and mismatch correction.

Exonuclease I (Exo I) from Schizosaccharomyces pombe, a 5'-->3' double-stranded DNA exonuclease, is induced during meiotic prophase I. The exo1 gene is a member of a family of related DNA repair genes, including RAD2/rad13/xpgc and YKL510/rad2, conserved from yeast to humans. An exo1 mutant displays a mutator phenotype and alters activity of the ade6-M387 marker effect. These results suggest that Exo I acts in a pathway that corrects mismatched base pairs.

Alleles↗
PubMed1995

The initiation and control of homologous recombination in Escherichia coli.

The chromosome of Escherichia coli recombines at low frequency when it is an intact circle but recombines at high frequency when it is broken, for example by X-rays, or when a linear DNA fragment is introduced into the cell during conjugation or transduction. The high recombinogenicity of double-strand (ds) DNA ends is attributable to RecBCD enzyme, which acts on ds DNA ends and is essential for recombination and ds DNA break repair. RecBCD enzyme initiates DNA unwinding at ds DNA ends, and its nuclease activity is controlled by Chi sites (5' G-C-T-G-G-T-G-G 3') in such a way that the enzyme produces a potent single-stranded DNA substrate for homologous pairing by RecA and single-stranded DNA binding proteins. We discuss a unifying model for recombination and ds DNA break repair, based upon the enzymic activities of these and other proteins and upon the behaviour of E. coli mutants altered in these proteins.

Escherichia coli↗
PubMed1995

A trial of the effect of a standardized psychiatric consultation on health outcomes and costs in somatizing patients.

BACKGROUND: Patients who somatize but who do not meet criteria for somatization disorder are common in the community. Virtually no research has been conducted to determine how to treat these patients. METHODS: We conducted a randomized controlled clinical trial of a psychiatric consultation intervention we had previously shown to improve the management of somatization disorder. The study population included 51 physicians treating 56 somatizing patients who had a history of seeking help for six to 12 lifetime unexplained physical symptoms. At the onset of the experiment, physicians randomized to the treatment condition received a consultation letter recommending a specific management approach; physicians randomized to the control/crossover condition received the consultation letter after 12 months. Data on health outcomes and charges were collected every 4 months for 2 years after randomization for 96% of subjects who entered the study. RESULTS: Patients of physicians who received the intervention reported significantly increased physical functioning, an improvement that remained stable during the year after the intervention. The intervention reduced annual medical care charges by $289 (95% confidence interval, $40 to $464) in 1990 constant dollars, which equates to a 32.9% reduction in the annual median cost of their medical care. CONCLUSIONS: Somatizing patients with a lifetime history of six to 12 unexplained physical symptoms reported better physical functioning after their primary care physician was provided appropriate treatment recommendations via a psychiatric consultation. Such a consultation is cost-effective because it reduces subsequent charges for medical care, while improving health outcomes in a chronically impaired population.

Adult↗
PubMed1995

Molecular cloning of the meiosis-induced rec10 gene of Schizosaccharomyces pombe.

The meiotic recombination gene rec10, which encodes a region-specific activator of recombination in Schizosaccharomyces pombe, has been cloned by genetic complementation and its nucleotide sequence determined. The rec10 gene was identified in a 5.6-kb cloned fragment by partial-deletion and insertion experiments. The nucleotide sequence of 3.5 kb of this clone revealed an open reading frame (ORF) encoding a 791 amino-acid polypeptide for the rec10 gene product. During meiosis, thermally induced in a temperature-sensitive pat1-114 mutant, the transcript of rec10 was induced to a maximal level at 2-3 h but was present at much lower levels before and after this time. The transient induction of the rec10 transcript and the rec10 mutant phenotype suggest that the rec10 gene product is involved primarily in the early steps of meiotic recombination localized to chromosome III in S. pombe.

Amino Acid Sequence↗
PubMed1995

Expression, purification, and use as an antigen of recombinant sugarcane mosaic virus coat protein.

A high titre (1:10,000) antiserum was raised in a rabbit against the coat protein of sugarcane mosaic potyvirus (SCMV), by injecting a preparation of recombinant coat protein purified from a fusion protein expressed in E. coli. The fusion protein consisted of the MalE maltose binding protein (MBP) and the viral coat protein separated by the protease factor Xa cleavage site. The fusion protein was encoded by the plasmid pMAL-cCPM, which was constructed by cloning a modified coat protein gene to the 3' end of the MBP/factor Xa coding region. The coat protein gene was modified by site-directed mutagenesis so that the ATG start codon in the original construct was replaced by the codon AGC, deleting the NcoI restriction site (C/CATGG) and creating a unique Eco47III site (AGC/GCT). Endonuclease restriction with Eco47III resulted in a DNA fragment with GCT as the first three nucleotides. This triplet encodes alanine, which is the proposed N-terminal amino acid residue of the mature native coat protein. This modified coat protein coding region was ligated directly behind the nucleotide code for the amino acid recognition sequence for factor Xa. Expression was induced with IPTG and the recombinant fusion protein was extracted from the bacterial lysate by amylose resin column affinity chromatography and the two domains separated by factor Xa proteolysis. The coat protein was then purified from the maltose binding protein by ion exchange chromatography in buffer containing 6 M urea. A highly purified sample which contained 150 micrograms of both full-length and truncated coat proteins, was recovered from a litre of bacterial broth. The antiserum reacted with native coat protein in SCMV-infected sugarcane, and with recombinant coat proteins expressed in E. coli and sugarcane protoplasts with little or no cross-reaction with sugarcane proteins.

Amino Acid Sequence↗