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Biomedical subjects

J M Becker

Publications and source records attributed to J M Becker.

At least 181 records · Page 10Linked to original sources
PubMed1985

Biological activity and conformational isomerism in position 9 analogues of the des-1-tryptophan,3-beta-cyclohexylalanine-alpha-factor from Saccharomyces cerevisiae.

Analogues of the des-1-tryptophan,3-beta-cyclohexylalanine-alpha-factor of Saccharomyces cerevisiae, where the glycyl residue of position 9 was replaced by D-Ala, L-Ala, D-Leu, and L-Leu, were synthesized and evaluated by morphogenesis assays and circular dichroism spectroscopy. Synthesis was accomplished in solution phase with mixed anhydrides and p-nitrophenyl active esters as the coupling agents. All crude dodecapeptides were purified to greater than 98% homogeneity by preparative high-performance liquid chromatography on a reversed-phase column. The Gly9, D-Ala9, and D-Leu9 analogues elicited morphogenic alterations in MATa strains of S. cerevisiae at concentrations of 1-2 micrograms/mL and exhibited similar CD patterns in both trifluoroethanol and tris(hydroxymethyl)aminomethane buffer, pH 7.4. In contrast, the L-Ala9 and L-Leu9 analogues were more than 200 times less active in the morphogenesis assay and had markedly different CD spectra. These results demonstrate that the position 9 residue plays an important role in determining the biological activity and solution conformation of alpha-factor. We suggest the presence of a type II beta-turn in the Lys7-Gln10 region when the alpha-factor assumes its biologically active conformation.

Alanine↗
PubMed1985

Structure-activity relationships in the dodecapeptide alpha-factor of Saccharomyces cerevisiae: position 6 analogues are poor inducers of agglutinability.

Five des-Trp1,Cha3,X6 analogues of alpha-factor, where X = Ala, Val, Ile, Nle, or D-Leu and X = Leu in the natural alpha-factor sequence, were prepared by solution-phase techniques utilizing isobutyl chloroformate or 1-hydroxybenzotriazole accelerated active esters as the coupling agents. Purification to 98% or greater homogeneity was accomplished by high-performance liquid chromatography on a reversed-phase muBondapak C18 column with methanol/water/trifluoroacetic acid as the mobile phase. Three of the synthesized analogues (X6 = Val, Ile, Nle) induced morphogenesis and increased agglutinability in a cells. These substitutions demonstrate that a gamma-branched side chain at position 6 is not essential for biological activity. All of the active analogues induced morphogenesis at lower concentrations than they induced enhanced agglutinability. These results and other structure-activity relationships [Baffi, R. A., Shenbagamurthi, P., Terrance, K., Becker, J. M., Naider, F., & Lipke, P. (1984) J. Bacteriol. 158, 1152-1156] indicate that the agglutination and morphological responses to alpha-factor can be varied independently. Replacement of Leu6 with Ala or D-Leu resulted in inactive analogues that were not antagonistic for alpha-factor activity. Cell-mediated hydrolysis experiments indicated that the biological activities of the alpha-factor analogues are independent of their rates of degradation. All position 6 analogues were hydrolyzed more slowly than the parent compound, suggesting that the enzyme which degrades alpha-factor is highly specific for the native structure.

Agglutination↗
PubMed1985

Effect of alcohol on cyclical myoelectric activity of the opossum sphincter of Oddi.

Ethyl alcohol may adversely affect pancreatic function by perturbing sphincter of Oddi (SO) or duodenal motor activity. The aim of this study was to identify the effect of ingested alcohol on the SO, duodenal, and gastric myoelectric activity in conscious opossums. In five adult opossums bipolar stranded stainless-steel wire electrodes were implanted on the SO, gastric antrum, and duodenum. After a 2-week recovery period, each animal underwent eight 8-hr recording sessions while fasted and awake. After two fasting cycles of the migrating myoelectric complex, animals were randomly fed either 10 ml of a 30% ethyl alcohol solution or 10 ml of water via an esophageal tube, and recordings continued for 4-6 hr. During the control state, cyclical myoelectric spike activity was recorded from the SO, gastric antrum, and duodenum with a mean +/- SD cycle length of 7.35 +/- 15.0 min, 74.3 +/- 10.1 min, and 94.8 +/- 8.7 min, respectively. With alcohol, SO and duodenal cycle lengths were unchanged while gastric cycle length decreased. However, alcohol effected a significant increase in peak SO spike burst frequency with no corresponding change in gastric or duodenal spike burst frequency. An equivalent volume of water had no influence on sphincter of Oddi myoelectric activity. It is concluded that ingested alcohol induces increased myoelectric activity from the opossum SO, independent of changes in activity of the duodenum or stomach. Since the SO plays a major role in metering bile and pancreatic flow into the duodenum, this may be a factor in alcohol-induced pancreatitis.

Ampulla of Vater↗
PubMed1985

Synthesis and biological activity of N epsilon-acyl derivatives of a Saccharomyces cerevisiae mating pheromone.

We report a general method for acylation of the N epsilon-amino group of the lysyl residue in peptides. The procedure involves acylation using p-nitrophenyl esters and 1-hydroxybenzotriazole in organic solvents to yield a series of fatty acyl mating pheromones of Saccharomyces cerevisiae. The fatty acyl group does not influence coupling of peptide fragments. Biological activities of the synthesized alpha-factor mating pheromones derivatized with acetyl, butyryl, caprylyl and lauryl groups are nearly equivalent to the activity of unacylated alpha-factor. The N epsilon-stearyl-alpha-factor is biologically inactive. The procedures reported in this communication can be used to increase hydrophobicity of lysine-containing peptides when the lysyl group is not essential for activity.

Animals↗
PubMed1985

Basal-cell carcinoma resulting from radiation therapy for hypertrophic tonsils.

Benign dermatologic conditions are no longer treated with therapeutic radiation because of the late complications that can result. One of the most serious complications that may occur is the development of skin cancer of various types. In this report, a patient received radiation for hypertrophic tonsils and later developed basal-cell carcinomas in the irradiated areas.

Basal Cell Carcinoma↗
PubMed1985

The ileoanal J pouch: radiographic evaluation.

Endorectal ileoanal pull-through offers an attractive alternative to proctocolectomy and ileostomy for patients with ulcerative colitis, Gardner syndrome, and familial polyposis. To our knowledge, a careful radiographic analysis of the ileum, ileal pouch, and ileoanal anastomosis after ileoanal pull-through has not been reported. Thirty-two patients with ulcerative colitis, Gardner syndrome, and familial polyposis underwent colectomy, mucosal proctectomy, and endorectal ileoanal pull-through of a 15-cm ileal "J" pouch and loop ileostomy. Twenty-five (78%) of 32 of all the pouches radiographically demonstrated spiral folds extending from the middle of the pouch to the pectinate line. Other radiographic features included a mesenteric mass effect, pseudopolyps, and a central lucency that indicated intrapouch sutures. Radiographs provide useful information in the postoperative management of the ileal pull-through.

Adult↗
PubMed1984

Anal sphincter function after colectomy, mucosal proctectomy, and endorectal ileoanal pull-through.

Anal sphincter function in patients before and after colectomy, mucosal proctectomy, and endorectal ileoanal pull-through was assessed prospectively. In 21 patients with ulcerative colitis, Gardner's syndrome, or familial polyposis, anorectal manometry was performed before and eight weeks after ileoanal pull-through. The mean +/- SEM maximal anal sphincter resting pressure decreased from 86 +/- 5 to 68 +/- 4 mm Hg after operation. The net change in pressure with squeeze, however, was greater after ileoanal pull-through than before operation (100 +/- 9 v 92 +/- 7 mm Hg). In 19 of 21 patients after operation, balloon dilation of the ileal pouch resulted in relaxation of the internal anal sphincter and contraction of the external anal sphincter. Mean +/- SEM 24-hour stool frequency decreased from 7.6 +/- 0.6 at one month to 6.2 +/- 0.5 at three months. It was concluded that ileoanal pull-through preserves continence and an acceptable stool frequency by maintaining nearly normal anal sphincter function.

Adolescent↗
PubMed1984

Different structure-function relationships for alpha-factor-induced morphogenesis and agglutination in Saccharomyces cerevisiae.

Eight synthetic analogs of the mating pheromone alpha-factor-induced morphogenesis and increased agglutinability in a cells. Most analogs induced increased agglutinability at lower concentrations than those at which they induced morphogenesis, but the ratio of the potencies for the two effects varied 140-fold among different analogs. Morphological response to pheromone required exposure for at least 90 min, but increased agglutinability followed exposures of 20 s. Two synthetic analogs induced neither response. In competition experiments, both of these analogs prevented induction of increased agglutinability and morphogenesis by active alpha factor. The inactive peptides blocked increased agglutinability at lower concentrations than those at which they blocked morphogenesis. alpha factors exhibited different structure-function relationships for morphogenesis as compared with agglutinability. Thus, response of Saccharomyces cerevisiae to alpha factor is complex and may be mediated by more than one receptor.

Agglutination↗
PubMed1984

Prognostic factors in pancreatic abscess.

Pancreatic abscess is a highly lethal sequela of pancreatitis. The purpose of this study was to identify clinical and laboratory factors associated with the antecedent episode of pancreatitis or at the time of manifestation of a pancreatic abscess and factors related to its treatment that might have prognostic significance. The records of 66 consecutive patients with pancreatic abscess seen between 1966 and 1980 were reviewed. Factors adversely affecting survival included: severity of precipitating pancreatitis (p less than 0.03); sepsis and pulmonary dysfunction (p less than 0.05); and persistent postoperative sepsis (p less than 0.001). All four patients who were treated nonsurgically died. Of 62 patients treated surgically, 80% experienced serious complications, 31% required reoperations, and 40% died. No single surgical procedure, including marsupialization, proved to be superior. Surgical drainage offers the only possibility of survival for patients with pancreatic abscess. More thorough elimination of all focuses of infection is required, however, to reduce the high morbidity and mortality rates associated with persistent postoperative sepsis.

Abscess↗
PubMed1983

Structure-activity relationships in the dodecapeptide alpha factor of Saccharomyces cerevisiae.

Ten analogues of His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr, the dodecapeptide alpha factor of Saccharomyces cerevisiae, were synthesized by conventional solution phase techniques and purified by using high-performance liquid chromatography. The dodecapeptide was also synthesized attached at its carboxyl terminus to poly(ethylene oxide), a macromolecular protecting group. Analogues in which Lys6 or His1 was modified exhibited high biological activity as evidenced by their ability to elicit aberrant morphologies in a cells of S. cerevisiae. These results suggest that neither a free alpha-amine nor a protonatable side chain at position 6 is necessary for biological activity of the dodecapeptide alpha factor. Although Ala2- and Phe2-dodecapeptides were not biologically active, they competed with the natural alpha factor and several active analogues. Thus binding of the alpha factor is not sufficient to elicit a biological response; it appears that the side chain in position 2 is critical for triggering morphological alterations in a cells.

Chromatography, High Pressure Liquid↗
PubMed1983

Inclusion cyst of the tunica albuginea: demonstration by ultrasound.

A 35-year-old man discovered a 1-cm nodule at the upper pole of the left testicle after blunt focal trauma. While the pain, tenderness, and location suggested hematoma or appendiceal torsion, the demonstration by ultrasound of the size, cystic nature, and extraparenchymal location was consistent with the rarely documented cyst of the tunica albuginea.

Adult↗
PubMed1983

Family conflict, psychopathology, and dangerous behavior by schizophrenic inpatients.

Data supporting the hypothesis that history of severe discipline and parental conflict in childhood is related to current violence were obtained in a study of 100 schizophrenic inpatients. In addition to a relation between inpatient violence and degree of schizophrenic symptoms, inpatient assaults and other dangerousness measures were positively and significantly correlated with severity of parental discipline, especially involving the father, and with degree of family conflict, particularly fights between parents and others outside the home.

Conflict, Psychological↗
PubMed1983

Design of anticandidal agents: synthesis and biological properties of analogues of polyoxin L.

Six analogues of polyoxin L were synthesized from uridine. All of these analogues inhibited chitin synthetase from Candida albicans. Derivatization of the amine terminus of the polyoxin analogues resulted in loss of activity, and analogues containing aromatic amino acid residues were the most efficient inhibitors of chitin synthetase. The concentration of tryptophanyl uracil polyoxin C, 8, which caused 50% inhibition of chitin synthetase activity, was 1.6 X 10(-6) M. This was virtually identical with the activity found for polyoxin D. None of the inhibitors effectively competed with the entry of (Met)3 into C. albicans. All of the analogues caused severe morphological distortions of the yeast in culture, and a number of analogues killed C. albicans at millimolar concentrations. The results suggest that chitin synthetase inhibitors may have potential as anticandidal drugs.

Antifungal Agents↗
PubMed1983

Transduodenal sphincteroplasty and transampullary septectomy for postcholecystectomy pain.

Ninety-two patients underwent a transduodenal sphincteroplasty and transampullary septectomy (extended papilloplasty) for chronic, incapacitating upper abdominal pain over an 11-year period. Seventy-nine had a prior cholecystectomy; 42 of 56 patients with reported pathology had documented gallstone disease. Serious morbidity included two moderately severe cases of postoperative pancreatitis and a pulmonary embolus. There were no deaths. Operative findings revealed stenosing papillitis (n = 45), transampullary septitis (n = 40), and papillary dysfunction (n = 7). Histologic examination of septal biopsy specimens revealed inflammation in 34 cases and fibrosis in 19 cases. There were no microscopic abnormalities in 39 biopsy specimens. The results at 1 to 10 years in 83 patients is as follows: good in 36 patients (no pain--43%), fair in 27 patients (occasional pain--33%), and poor in 20 patients (unrelieved by the procedure--24%). Patients with prior sphincteroplasty (12 of 15 with a fair to good result) benefitted the most from the procedure. Those who underwent concomitant cholecystectomy responded poorly. Risk factors for failure include alcoholism, drug addiction, mental illness, and duodenal ulcer disease. The finding of papillary cholesterolosis at operation also was accompanied by a less than optimal result. Transduodenal sphincteroplasty with transampullary septectomy provides long-term benefit to carefully selected patients with chronic abdominal pain after cholecystectomy.

Abdomen↗