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S K Mann

Publications and source records attributed to S K Mann.

At least 37 records · Page 2Linked to original sources
PubMed1989

Molecular analysis of a developmentally regulated gene required for Dictyostelium aggregation.

We have previously shown that the developmentally regulated gene D2 is induced during aggregation by pulses of cAMP, which act via the cell surface receptor and consequent signal transduction pathways (W. Rowekamp and R.A. Firtel, 1980, Dev. Biol. 79, 409-418; S.K.O. Mann and R.A. Firtel, 1987, Mol. Cell. Biol. 7, 458-469; S.K.O. Mann, C. Pinko, and R.A. Firtel, 1988, Dev. Biol., in press). In this manuscript, we compare the complete derived amino acid sequence for D2 to two cloned and sequenced eukaryotic esterases and examine the requirement of the D2 gene product for development. Amino acid sequence data comparisons suggest that D2 encodes a serine esterase with strong sequence identity to Torpedo acetylcholine esterase and a Drosophila esterase. The protein has a putative leader sequence, suggesting that it is shunted into vesicles. Using an antisense gene construct driven by a Discoidin I promoter, whose transcriptional activity depends on the growth conditions of the cells, we show that inhibition of D2 mRNA accumulation results in an abnormal developmental program that includes the absence of normal streaming and incomplete aggregate formation and subsequent development. We suggest that D2 encodes an esterase function required for proper aggregation and subsequent development.

Acetylcholinesterase↗
PubMed1989

Two-phase regulatory pathway controls cAMP receptor-mediated expression of early genes in Dictyostelium.

Two classes of early genes in Dictyostelium are differentially regulated by extracellular pulses of cAMP interacting with its cell-surface receptor, conditions that also regulate chemotaxis and aggregation. The pulse-repressed genes, such as K5, are induced shortly after the onset of starvation and are repressed a few hr later during aggregation by cAMP pulses. The pulse-induced genes (including D2, M3, and those encoding contact sites A, the G alpha protein subunit G alpha 2, and the cell-surface cAMP receptor) are maximally induced just prior to aggregation by pulses of cAMP and are subsequently repressed by sustained moderate levels of cAMP--conditions that exist sequentially in development. In this manuscript, we further analyze the requirement for cAMP pulses and characterize a requirement for protein synthesis for the expression of these two classes of genes. Our results indicate that the control of expression of both the pulse-induced and pulse-repressed genes requires other developmentally regulated factors in addition to starvation and cAMP pulses. We also identified another early gene, F9, whose expression is stimulated upon starvation, is not responsive to cAMP, and is hyperstimulated by cycloheximide, in a manner similar to the cycloheximide stimulation of c-fos and other serum-induced genes in mammalian cells. Examination of the kinetics of expression of the pulse-induced genes in a mutant blocked in the cAMP relay pathway indicates that their expression is controlled by a two-phase process. The first phase requires starvation and CMF, an extracellular conditioned medium factor, and results in a low level of expression. The second phase requires establishment of the cAMP signal-relay system and induces the genes to a high level. Both phases require prior and concomitant protein synthesis. Some of the members of the pulse-induced class encode elements of the cAMP signal-relay system that controls aggregation, indicating a feedback autoregulation. The two-phase process might allow the "finetuning" of the level of expression of genes involved in aggregation.

Adenylyl Cyclases↗
PubMed1988

Control of early gene expression in Dictyostelium.

We have examined the expression of a cAMP pulse-repressed and two cAMP pulse-induced genes in response to cAMP and caffeine under a number of different physiological conditions, and in several classes of development mutants altered in cAMP-mediated signal transduction pathways. The data presented help characterize the mutants with regard to early gene expression. Analysis of the data indicates that full induction of the pulse-induced or repression of the pulse-repressed genes requires cycles of activation and adaptation of the cAMP receptor but does not require a rise in intracellular cAMP. Comparison of the results obtained between different mutant classes suggests that repression and activation of the two classes of genes can be uncoupled, implying that different intracellular mechanisms control these processes. In addition, we examined the effects of caffeine and show that it can induce pulse-induced mRNA accumulation in the absence of cAMP.

Caffeine↗
PubMed1988

cAMP regulation of early gene expression in signal transduction mutants of Dictyostelium.

We have examined the regulation of three early developmentally regulated genes in Dictyostelium. Two of these genes (D2 and M3) are induced by pulses of cAMP and the other (K5) is repressed. Expression of these genes has been examined in a number of developmental mutants that are specifically blocked in various aspects of the signal transduction/cAMP relay system involved in aggregation and control of early development. The mutant strains include Synag mutants, which are blocked in receptor-mediated activation of adenylate cyclase and do not relay cAMP pulses; FrigidA mutants, which are blocked in receptor-mediated activation of both adenylate cyclase and the putative phosphoinositol bisphosphate (PIP2) turnover pathway and appear to be mutations in the gene encoding one of the G alpha protein subunits; and a StreamerF allele, which lacks cGMP-specific cGMP phosphodiesterase. From the analysis of the developmental expression of these genes under a variety of conditions in these mutant strains, we have drawn a number of conclusions concerning the modes of regulation of these genes. Full induction of D2 and M3 genes requires cAMP interaction with the cell surface receptor and an "oscillation" of the receptor between active and adapted forms. Induction of these genes does not require activation of the signal transduction pathway that leads to adenylate cyclase activation and cAMP relay, but does require activation of other receptor-mediated intracellular signal transduction pathways, possibly that involving PIP2 turnover. Likewise, repression of the K5 gene requires pulses of cAMP. Expression of this gene is insensitive to cAMP pulses in FrigidA mutants, suggesting that a signal transduction pathway is necessary for its repression. Results using the StreamerF mutant suggest that the rise in cGMP in response to cAMP/receptor interactions may not be directly related to control of the pulse-induced genes. In addition, we have examined the effect of caffeine, which M. Brenner and S.D. Thomas (1984, Dev. Biol., 101, 136-146) showed preferentially blocks the cAMP relay system by blocking receptor-mediated activation of adenylate cyclase. We show that in many of the mutants and in an axenic wild-type strain, caffeine causes the induction of pulse-induced gene expression to almost wild-type levels or in some cases to higher than wild-type levels. Our data suggest that caffeine works by activating some step in the signal transduction pathway that must lie downstream from both the receptor and at least one of the G proteins and thus has effects other than simply blocking the receptor-mediated cAMP relay system.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1987

Cyclic AMP regulation of early gene expression in Dictyostelium discoideum: mediation via the cell surface cyclic AMP receptor.

We examined two sets of genes expressed early in the developmental cycle of Dictyostelium discoideum that appear to be regulated by cyclic AMP (cAMP). The transcripts of both sets of genes were not detectable in vegetative cells. During normal development on filter pads, RNA complementary to these genes could be detected at about 2 h, peaked around 6 to 8 h, and decreased gradually thereafter. Expression of these genes upon starvation in shaking culture was stimulated by pulsing the cells with nanomolar levels of cAMP, a condition that mimics the in vivo pulsing during normal aggregation. Expression was inhibited by caffeine or by continuous levels of cAMP, a condition found later in development when in vivo expression of these genes decreased. The inhibition of caffeine could be overcome by pulsing cells with cAMP. These results suggest that the expression is mediated via the cell surface cAMP receptor, but does not require a rise in intracellular cAMP. mRNA from a gene of the second class was induced upon starvation, peaked by 2.5 h of development, and then declined. In contrast to the other genes, its expression was maintained by continuous levels of cAMP and repressed by cAMP pulses. These and other results on a number of classes of developmentally regulated genes indicates that changing levels of cAMP, acting via the cell surface cAMP receptor, are involved in controlling these groups of genes. We also examined the structure and partial sequence of the cAMP pulse-induced genes. The two tandemly duplicated M3 genes were almost continuously homologous over the sequenced portion of the protein-coding region except for a region near the N-terminal end. The two M3 genes had regions of homology in the 5' flanking sequence and showed slight homology to the same regions in gene D2, another cAMP pulse-induced gene. D2 showed extremely significant homology over its entire sequenced length to an acetylcholinesterase. The results presented here and by others suggest that expression of many early genes in D. discoideum is regulated via the cell surface cAMP receptor. We expect that many of these genes may play essential roles in early Dictyostelium development and could code for elements of the cAMP signal transduction pathway involved in aggregation.

Amino Acid Sequence↗
PubMed1984

Nasoenteral feeding tube insertion via fiberoptic endoscope for enteral hyperalimentation.

Total parenteral nutrition can maintain good nutritional status in selected patients. However, it can be accompanied by serious complications. It is generally agreed that enteral alimentation is more economical and safer. Gut should be used for nutritional replenishment whenever feasible. However, large-bore nasogastric feeding tubes can cause problems. Even fine-bore nasogastric tubes can cause aspiration pneumonia in obtunded and debilitated patients. In some patients it is clearly desirable to have the tip of the feeding tube in the distal duodenum or proximal jejunum. Previously described methods for placement of nasoenteral tubes may be unsatisfactory. We describe a safe, simple, and reliable method for endoscopic insertion of fine-bore nasoenteral feeding tube. We have used this method on 15 patients without complication.

Aged↗
PubMed1981

Infecundity and dominant lethal mutations induced in Musca domestica L. by sodium azide (NaN3).

Results of our study suggest that sodium azide is effective in the induction of sterility and dominant lethal mutations in both sexes of M. domestica L. When treated males were crossed with nontreated females, 100% dominant lethal mutations and 72.3% infecundity were found, whereas in the crosses of nontreated males and treated females, 82.5% dominant lethal mutations and 33.1% infecundity were found. This showed that males are more sensitive to sodium azide than females.

Animals↗
PubMed1980

Fiberoptic colonoscopic study of experimental chemical colitis.

Acute diffuse chemical colitis was produced in rats with a high degree of reproducibility by the intracolonic administration of 10% acetic acid. The evolution and progression of this colitis was followed by performing serial fiberoptic colonoscopy using a needlescope and biopsy. Hyperemia appeared at 10 hours and ulcerations appeared at 24 hours in acetic acid-treated animals. After 3 days, the ulcers were covered with a yellowish exudate. At 8 weeks there was endoscopic and histologic healing of the lesions. No changes occurred in the saline-treated animals. Concomitant topical applications of epsilon-aminocaproic acid protected against acetic acid-induced injury.

Aminocaproates↗
PubMed1979

Effect of lactulose, neomycin and antacid on colonic pH recorded continuously with an implanted electrode.

Colonic pH was continuously monitored by a pH electrode implanted in the transverse colon of rats over a 24-hour period. Lactulose significantly reduced the colonic pH to 5.37 +/- .39 from a fasting value of 6.77 +/- .75. Pretreatment with neomycin or concomitant use of a nonabsorbable antacid prevented lactulose-induced reduction in the colonic pH. The clinical implication of the study is that combined use of lactulose with neomycin or high doses of non-absorbable antacids in the treatment of chronic portasystemic encephalopathy may be undesirable.

Animals↗
PubMed1979

Pancreatic Ascites.

Ascites occurring in patients with a history of alcoholism is usually due to cirrhosis but clinically significant ascites also occurs in association with pancreatic disease. We reviewed 265 cases of pancreatitis over a five-year period. There were 129 blacks and 136 Caucasians. Ages ranged from 19-86 years with a mean of 46.2 years. Eight of these cases (3%) were found to have pancreatic ascites. The initial serum and urinary amylase had no prognostic value regarding the subsequent development of pancreatic ascites. The mean ascitic fluid amylase was 14,426 Somogyi units (range 1,279-67,774). The mean ascitic fluid protein was 4.6 gm./100ml. (range 1.4-7.2). High enzyme and protein concentration in the ascitic fluid are characteristic of pancreatic ascites. Out of eight cases, two were associated with a pseudocyst, three with hemorrhagic pancreatitis and three with acute edematous pancreatitis. Four of these eight (50%) died. Pancreatic ascites is a distinct clinical entity which should be differentiated from cirrhotic, tuberculous or malignant ascites.

Adult↗