Allergic contact dermatitis from tall oil in undiluted soluble oils used as releasing fluids.
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Dermatitis, Allergic Contact↗
Biomedical subjects
H Nelson
Publications and source records attributed to H Nelson.
Altered distribution of the yeast plasma membrane H+-ATPase as a feature of vacuolar H+-ATPase null mutants.
The effect of vacuolar H(+)-ATPase (V-ATPase) null mutations on the targeting of the plasma membrane H(+)-ATPase (Pma1p) through the secretory pathway was analyzed. Gas1p, which is another plasma membrane component, was used as a control for the experiments with Pma1p. Contrary to Gas1p, which is not affected by the deletion of the V-ATPase complex in the V-ATPase null mutants, the amount of Pma1p in the plasma membrane is markedly reduced, and there is a large accumulation of the protein in the endoplasmic reticulum. Kex2p and Gef1p, which are considered to reside in the post-Golgi vesicles, were suggested as required for the V-ATPase function; hence, their null mutant phenotype should have been similar to the V-ATPase null mutants. We show that, in addition to the known differences between those yeast phenotypes, deletions of KEX2 or GEF1 in yeast do not affect the distribution of Pma1p as the V-ATPase null mutant does. The possible location of the vital site of acidification by V-ATPase along the secretory pathway is discussed.
Cell Membrane↗
The family of SMF metal ion transporters in yeast cells.
Metal ions are vital for all organisms, and metal ion transporters play a crucial role in maintaining their homeostasis. The yeast (Saccharomyces cerevisiae) Smf transporters and their homologs in other organisms have a central role in the accumulation of metal ions and their distribution in different tissues and cellular organelles. In this work we generated null mutations in each individual SMF gene in yeast as well as in all combinations of the genes. Each null mutation exhibited sensitivity to metal ion chelators at different concentrations. The combination of null mutants DeltaSMF1 + DeltaSMF2 and the triple null mutant Delta3SMF failed to grow on medium buffered at pH 8 and 7.5, respectively. Addition of 5 microm copper or 25 microm manganese alleviated the growth arrest at the high pH or in the presence of the chelating agent. The transport of manganese was analyzed in the triple null mutant and in this mutant expressing each Smf protein. Although overexpression of Smf1p and Smf2p resulted in uptake that was higher than wild type cells, the expression of Smf3p gave no significant uptake above that of the triple mutant Delta3SMF. Western analysis with antibody against Smf3p indicated that this transporter does not reach the plasma membrane and may function at the Golgi or post-Golgi complexes. The iron uptake resulting from expression of Smf1p and Smf2p was analyzed in a mutant in which its iron transporters FET3 and FET4 were inactivated. Overexpression of Smf1p gave rise to a significant iron uptake that was sensitive to the sodium concentrations in the medium. We conclude that the Smf proteins play a major role in copper and manganese homeostasis and, under certain circumstances, Smf1p may function in iron transport into the cells.
Amino Acid Sequence↗
Cloning and expression of cDNAs encoding plant V-ATPase subunits in the corresponding yeast null mutants.
Complementation of yeast null mutants is widely used for cloning of homologous genes from heterologous sources. We have used this method to clone the relevant V-ATPase genes from lemon fruit and Arabidopsis thaliana cDNA libraries. The pH levels are very different in the vacuoles of the lemon fruit and the A. thaliana, yet both are the result of the activity of the same enzyme complex, namely the V-ATPase. In order to investigate the mechanism that enables the enzyme to maintain such differences in pH values, we have compared the subunit composition of the V-ATPase complex from both sources. Towards this end, we have constructed a cDNA library from lemon fruit and cloned it into a similar shuttle vector to the one of the A. thaliana cDNA library, which is commercially available. In this work, we report the cloning and expression of VMA10 from both sources, two isoforms of the lemon proteolipid (VMA3) and the lemon homologue of yeast VPH1/STV1 subunit, LEMAC.
Amino Acid Sequence↗
Exclusion limits on the WIMP-nucleon cross section from the cryogenic dark matter search.
The Cryogenic Dark Matter Search (CDMS) employs Ge and Si detectors to search for weakly interacting massive particles (WIMPs) via their elastic-scattering interactions with nuclei while discriminating against interactions of background particles. CDMS data, accounting for the neutron background, give limits on the spin-independent WIMP-nucleon elastic-scattering cross section that exclude unexplored parameter space above 10 GeV/c2 WIMP mass and, at >75% C.L., the entire 3sigma allowed region for the WIMP signal reported by the DAMA experiment.
Journal Article↗
Wound recurrences following laparoscopic-assisted colectomy for cancer.
OBJECTIVES: To determine the incidence and clinical relevance of wound recurrences (WRs) following laparoscopic-assisted colectomy for cancer; to analyze the most recent experimental studies examining possible pathogenic mechanisms; and to delineate possible prevention strategies. DATA SOURCES: A MEDLINE search was conducted using the words "colectomy," "laparoscopy," and "recurrence, local." Additional articles were retrieved by cross-referencing. STUDY SELECTION: All clinical and experimental studies retrieved were reviewed and subjectively selected according to their relevance for clinical practice. DATA EXTRACTION: Clinical data from 1990 to 2000 with series analyzing 50 or more patients were preferentially considered. Experimental data were considered based on the most rigorous study designs and the potential impact of experimental findings on clinical practice. DATA SYNTHESIS: The incidence of WRs in large series and based on current techniques is comparable to what has been reported for WR following open colectomy. While the pathogenesis of early WR occurrences remains unclear, experience and appropriate training in laparoscopic-assisted colectomy are essential to minimize the incidence of WRs. Results from experimental studies are still controversial, and available data from prospective randomized clinical trials are still limited. CONCLUSIONS: Results from prospective randomized trials are needed to provide definitive answers regarding the incidence and survival impact of WRs. Until then, WR may be considered a technical complication following laparoscopic-assisted colectomy.
Animals↗
Laparoscopic right colectomy: five-step procedure.
The advanced laparoscopic skills required for laparoscopic resection of the colon and rectum have precluded wide dissemination of this procedure. By applying certain key principles, laparoscopic right hemicolectomy can be made simple, reproducible, easy to teach, easy to learn, and cost-effective.
Colectomy↗
Safety and advantages of laparoscopic vs. open colectomy in the elderly: matched-control study.
PURPOSE: The aim of this study was to determine rates of complications and extent of benefits for laparoscopic-assisted colectomy compared with open colectomy in patients older than age 75. METHODS: Forty-two patients undergoing laparoscopic-assisted colectomy (1992-1998) were matched to 42 open colectomy patients for gender, age, year of surgery, operating surgeon, and procedure. Health status (American Society of Anesthesiology score), previous abdominal surgery, conversion rate, surgical outcome, and need for assistance at admission and dismissal (independence vs. home with assistance vs. nursing facilities) were reviewed. RESULTS: Mean ages were 81.2 and 80.5 years for laparoscopic-assisted colectomy and open colectomy, respectively (P = not significant). Twenty-one laparoscopic-assisted colectomy and 23 open colectomy patients were females. American Society of Anesthesiology scores were comparable, as were rates of previous abdominal surgery (57 percent for laparoscopic-assisted colectomy vs. 62 percent for open colectomy; P = not significant). Mean operative times were longer for laparoscopic-assisted colectomy (190 minutes for laparoscopic-assisted colectomy vs. 142 minutes for open colectomy; P < 0.001); operating room times progressively decreased from 221 minutes in 1992 to 1995 to 147 in 1998 for laparoscopic right hemicolectomy (P < 0.001). The conversion rate for laparoscopic-assisted colectomy was 14.3 percent. There were no deaths in either group, and laparoscopic-assisted colectomy was associated with fewer morbidities (14.3 percent for laparoscopic-assisted colectomy vs. 33.3 percent for open colectomy; P = 0.04), narcotic usage (2.7 vs. 4.8 days; P < 0.001), time to return to bowel movements (3.9 vs. 5.9 days; P < 0.001), and length of hospital stay (6.5 vs. 10.2 days; P < 0.001). Independent status at admission in 37 laparoscopic-assisted colectomy and 38 open colectomy patients was maintained at discharge by 35 laparoscopic-assisted colectomy vs. 29 open colectomy patients (P = 0.025). CONCLUSIONS: Laparoscopic-assisted colectomy is safe and beneficial, including preservation of postoperative independence, to the elderly when compared with open colectomy.
Aged↗
Sacropelvic resection for recurrent anorectal cancer. A multidisciplinary approach.
A multimodal approach including preoperative external beam radiation, surgical resection, and intraoperative electron radiation was used in 23 patients with locally advanced anal or recurrent rectal cancers involving the sacrum. The proximal extent of complete sacral resection was S2 in three patients, S3 in 12 patients, S4 in two patients, and S5 in one patient. The tumor was confined to the anterior sacral cortex in five patients. The resection was marginal in 10, contaminated marginal in 11, and intralesional in two patients. At 19 to 54 months of followup, five patients are alive without evidence of disease and four are alive with disease. Twelve patients died of their disease, and two died of other causes. There was a mean survival of 32.9 months for the patients who were alive at followup. Kaplan-Meier survival for all patients was 82% at 1 year and 73% at 2 years, with death of disease as an endpoint. Thirteen (57%) patients had another local recurrence develop at a mean of 17.2 months. Eight (35%) patients had metastatic disease develop at a mean of 16.3 months. Proper patients selection is important in ensuring a favorable outcome from this aggressive surgery.
Adenocarcinoma↗
The cellular biology of proton-motive force generation by V-ATPases.
The vacuolar H(+)-ATPase (V-ATPase) is one of the most fundamental enzymes in nature. It functions in almost every eukaryotic cell and energizes a wide variety of organelles and membranes. In contrast to F-ATPases, whose primary function in eukaryotic cells is to form ATP at the expense of the proton-motive force, V-ATPases function exclusively as ATP-dependent proton pumps. The proton-motive force generated by V-ATPases in organelles and across plasma membranes of eukaryotic cells is utilized as a driving force for numerous secondary transport processes. The enzyme is also vital for the proper functioning of endosomes and the Golgi apparatus. In contrast to yeast vacuoles, which maintain an internal pH of approximately 5. 5, it is believed that the vacuoles of lemon fruit may have a pH as low as 2. Similarly, some brown and red algae maintain an internal pH as low as 1 in their vacuoles. It was yeast genetics that allowed the identification of the special properties of individual subunits and the discovery of the factors that are involved in V-ATPase biogenesis and assembly. Null mutations in genes encoding V-ATPase subunits of Saccharomyces cerevisiae result in a phenotype that is unable to grow at high pH and is sensitive to high and low metal-ion concentrations. Treatment of these null mutants with ethyl methanesulphonate causes mutations that suppress the V-ATPase null phenotype, and these cells are able to grow at pH 7.5. The suppressor mutants were denoted as svf (Suppressor of V-ATPase Function). The svf mutations are recessive: crossing the svf mutants with their corresponding V-ATPase null mutants resulted in diploid strains that were not able to grow at pH 7.5. A novel gene family in which null mutations cause pleiotropic effects on metal-ion resistance or on the sensitivity and distribution of membrane proteins in different targets was discovered. We termed this gene family VTC (Vacuolar Transporter Chaperon) and discovered four genes in S. cerevisiae that belong to the family. Inactivation of one of them, VTC1, in the background of V-ATPase null mutations resulted in an svf phenotype that was able to grow at pH 7.5. Apparently, Vtc1p is one of a few membrane organizers that determine the relative amounts of different membrane proteins in the various cellular membranes. We utilize the numerous yeast mutants generated in our laboratory to identify the specific organelle whose acidification is vital. The interaction between V-ATPase and the secretory pathway is investigated.
Amino Acid Sequence↗
Benefits of laparoscopic-assisted colectomy for colon polyps: a case-matched series.
OBJECTIVE: To clarify the true benefits of laparoscopic-assisted colectomy by comparing clinical outcomes from a series of laparoscopic right colectomies with matched open colectomies, all performed for the singular indication of polyp not amenable to colonoscopic removal. PATIENTS AND METHODS: A retrospective case-matched study was performed of consecutive patients undergoing laparoscopic-assisted right hemicolectomy for polyps between January 1992 and July 1997. Each case was matched to a control undergoing the equivalent open procedure for the same indication during the same time period. RESULTS: Thirty-eight patients undergoing laparoscopic-assisted right hemicolectomy for polyps were identified, and matches were found. The conversion rate was 18.4% (7/38), 21.4% early in the series and 10% in later experience. Operative times were longer for laparoscopic-associated colectomy (median, 208 minutes vs 150 minutes, P < .001). Laparoscopic-assisted colectomy resulted in shorter postoperative ileus (time to flatus, 3.0 vs 4.0 days, P < .001; time to bowel movement, 3.5 vs 5.0 days, P < .001) and in earlier tolerance of regular diet (3.5 vs 6.0 days, P < .001). Fewer days of narcotic administration were required by the laparoscopic group (3.0 vs 4.5 days, P < .001). This resulted in a significantly shorter length of hospital stay (4.0 vs 7.0 days, P < .001). There was no significant difference in the incidence of postoperative complications. CONCLUSIONS: Laparoscopic right hemicolectomy has significant patient benefits. These benefits are apparent when procedures of equal complexity and equivalent indications are compared. Laparoscopic-assisted resection has become our preferred approach for polyps not amenable to colonoscopic polypectomy.
Aged↗
Laparoscopic colon and rectal surgery.
There are disparate variables available to appraise the quality of the laparoscopic colorectal surgery. Currently available data suggest that laparoscopic colectomy can be completed safely in most cases. It is feasible and offers patient-related benefits similar to those described for other laparoscopic procedures. The framework, within which the quality of laparoscopic colon and rectum surgery is appraised and judged, is discussed with an emphasis on diverse outcomes used to measure quality.
Benchmarking↗
Laparoscopic approach to colon cancer.
At present, the laparoscopic approach for colon cancer must be regarded as a developmental procedure. Although laparoscopic colectomy has repeatedly been demonstrated to be feasible, safe, and reasonable, analysis of cancer control, health care costs, and quality of life are needed. Questions remain, particularly with respect to recurrence and survival outcomes. All current clinical trials should be viewed as early and inconclusive, despite optimism expressed by some and pessimism by others. Therefore, patients undergoing laparoscopic colectomy for carcinoma should be enrolled in prospective randomized trials. This is the only manner of conclusively resolving current controversies. The authors have enthusiasm for the future of laparoscopic colectomy for cancer even though it is necessary to wait for results from the controlled trials.
Colonic Neoplasms↗
Effects of laparoscopy on tumor growth.
Laparoscopic resections of colon cancer may affect survival. To address the effects of pneumoperitoneum on tumor cell biology, we developed an experimental model. Mice were injected with colonic tumor cells. Local and systemic effects of pneumoperitoneum were evaluated. Treated mice were randomly assigned to a control group, an open cecectomy group, or a laparoscopic-simulated cecectomy group. When a tumor inoculum was injected into the peritoneal cavity, the frequency of tumors was not significantly different for mice in the laparoscopic-simulated and open cecectomy groups (60% vs 62%, respectively). There was no significant difference in survival time between the laparoscopic-simulated and open cecectomy groups, with median survivals of 24 days versus 22 days, respectively. Finally, when tumor cells were injected subcutaneously, the frequency of tumor nodules and the size and weight of tumors were not different between the two surgical groups. Laparoscopic-simulated cecectomy does not appear to adversely effect local factors or favorably affect systemic factors influencing tumor growth or survival.
Adenocarcinoma↗
Yeast SMF1 mediates H(+)-coupled iron uptake with concomitant uncoupled cation currents.
Yeast membrane proteins SMF1, SMF2, and SMF3 are homologues of the DCT1 metal ion transporter family. Their functional characteristics and the implications of these characteristics in vivo have not yet been reported. Here we show that SMF1 expressed in Xenopus oocytes mediates H(+)-dependent Fe(2+) transport and uncoupled Na(+) flux. SMF1-mediated Fe(2+) transport exhibited saturation kinetics (K(m) = 2.2 microM), whereas the Na(+) flux did not, although both processes were electrogenic. SMF1 is also permeable to Li(+), Rb(+), K(+), and Ca(2+), which likely share the same uncoupled pathway. SMF2 (but not SMF3) mediated significant increases in both Fe(2+) and Na(+) transport compared with control oocytes. These data are consistent with the concept that uptake of divalent metal ions by SMF1 and SMF2 is essential to yeast cell growth. Na(+) inhibited metal ion uptake mediated by SMF1 and SMF2 expressed in oocytes. Consistent with this, we found that increased sensitivity of yeast to EGTA in the high Na(+) medium is due to inhibition of SMF1- and SMF2-mediated metal ion transport by uncoupled Na(+) pathway. Interestingly, DCT1 also mediates Fe(2+)-activated uncoupled currents. We propose that uncoupled ion permeabilities in metal ion transporters protect cells from metal ion overload.
Animals↗
A novel family of yeast chaperons involved in the distribution of V-ATPase and other membrane proteins.
Null mutations in genes encoding V-ATPase subunits in Saccharomyces cerevisiae result in a phenotype that is unable to grow at high pH and is sensitive to high and low metal-ion concentrations. Treatment of these null mutants with ethylmethanesulfonate causes mutations that suppress the V-ATPase null phenotype, and the mutant cells are able to grow at pH 7.5. The suppressor mutants were denoted as svf (suppressor of V-ATPase function). The frequency of svf is relatively high, suggesting a large target containing several genes for the ethylmethanesulfonate mutagenesis. The suppressors' frequency is dependent on the individual genes that were inactivated to manifest the V-ATPase null mutation. The svf mutations are recessive, because crossing the svf mutants with their corresponding V-ATPase null mutants resulted in diploid strains that are unable to grow at pH 7.5. A novel gene family in which null mutations cause pleiotropic effects on metal-ion resistance or sensitivity and distribution of membrane proteins in different targets was discovered. The family was defined as VTC (Vacuolar Transporter Chaperon) and it contains four genes in the S. cerevisiae genome. Inactivation of one of them, VTC1, in the background of V-ATPase null mutations resulted in svf phenotype manifested by growth at pH 7.5. Deletion of the VTC1 gene (DeltaVTC1) results in a reduced amount of V-ATPase in the vacuolar membrane. These mutant cells fail to accumulate quinacrine into their vacuoles, but they are able to grow at pH 7.5. The VTC1 null mutant also results in a reduced amount of the plasma membrane H(+)-ATPase (Pma1p) in membrane preparations and possibly mis-targeting. This observation may provide an explanation for the svf phenotype in the double disruptant mutants of DeltaVTC1 and DeltaVMA subunits.
Amino Acid Sequence↗
Carcinogen exposure, p53 alteration, and K-ras mutation in synchronous multiple primary lung carcinoma.
BACKGROUND: Synchronous multiple primary lung tumors (SMPLT) have been estimated to occur in 1% of lung carcinoma patients. Criteria for SMPLT diagnosis include different cancer histologies, location in different lobes of the lung, or genetic discordance. Patients with SMPLT have a poor clinical prognosis with decreased 5-year disease survival, despite diagnosis at an early stage. Field cancerization (the induction of somatic mutation in large clones of epithelial cells after carcinogen exposure) has been proposed to be an integral process involved in the development of SMPLT. Host factors also may contribute to the development of SMPLT. METHODS: The authors investigated the occurrence of p53 and K-ras alterations in tumors from SMPLT patients and also studied the association between carcinogen exposure and polymorphic metabolic traits in SMPLT patients, comparing these patients with individuals with one primarily lung tumor. RESULTS: In a case-control study of lung carcinoma susceptibility, 6 patients were identified whose 33 multiple tumors met the criteria of SMPLT. The incidence was 3.6% (16 of 451 patients), which was higher than many previously published series. Among the multiple tumors, 73% (24 of 33 tumors) were adenocarcinomas. Patients with SMPLT smoked more (73.0 pack-years vs. 56.2 pack-years; P = 0.07) and longer (45.8 years vs. 37.0 years; P < 0.03) than patients with only 1 tumor. For those patients who stopped smoking, patients with SMPLT had stopped smoking more recently than those with a single primary tumor (3.4 years vs. 7.3 years; P = 0.08). A total of 39% of SMPLT tumors (13 of 33 tumors) had detectable p53 alterations; 36% had genetic changes in p53 measured by polymerase chain reaction-single strand conformation polymorphism, and 33% showed positive immunostaining for p53 protein. This was comparable to the occurrence of p53 mutations and immunostaining in single tumor cases (30%). Age, gender, family history of cancer, and the prevalence of polymorphic metabolic traits previously associated with lung carcinoma susceptibility did not differ among SMPLT patients compared with patients with a single tumor. CONCLUSIONS: The patients with SMPLT had significantly more tobacco exposure, and their tumors apparently had independently arising p53 and K-ras mutations, suggesting that field cancerization may be important in lung carcinogenesis.
Adenocarcinoma↗
The incidence and clinical consequences of treatment-related bowel injury.
OBJECTIVE: To assess the frequency and clinical features of treatment-induced bowel injury in rectal carcinoma patients receiving perioperative external beam radiotherapy (EBRT). The frequency of and factors associated with treatment-induced intestinal injury have previously not been well quantified for rectal cancer patients. Postoperative adjuvant chemoirradiation is recommended for Stage II and III rectal cancers, making such data of significant interest. METHODS AND MATERIALS: The records of 386 consecutive patients undergoing radiotherapy with or without chemotherapy (CT) for rectal carcinoma between 1981-90 were reviewed. Eight-two patients were excluded for receiving nontherapeutic EBRT or modalities other than EBRT. RESULTS: Symptomatic acute treatment-related enteritis (within 30 days of EBRT +/- CT) was diagnosed in 13 patients, 3 of whom developed chronic bowel injury. Chronic treatment-related enteritis was identified in 18 patients and reoperation was required in 17 (5% of the 304 patients with complete follow-up). Chronic proctitis was documented in 38 patients, including 3 patients with small bowel injury. The probability of developing treatment-induced bowel injury at 5 years following treatment was 19%. Variables associated with an increased risk of bowel injury using multivariate analysis were transanal excision (p = 0.002), escalating radiation dose (p = 0.005), and increasing age (p = 0.01). Twenty of the affected patients required operative treatment, and 2 deaths resulted from treatment-induced enteritis. CONCLUSION: Patients with rectal carcinoma treated with EBRT +/- CT have the risk of developing treatment-induced bowel injury. The pelvic radiation dose should be limited to < or = 5040 cGy unless small bowel can be displaced. Reperitonealization of the pelvis, or other surgical methods of excluding the small intestine should be used whenever possible.
Aged↗