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Biomedical subjects

J M Becker

Publications and source records attributed to J M Becker.

At least 145 records · Page 8Linked to original sources
PubMed1989

Hepatic hemangioendotheliomas in infancy.

Multicentric hepatic hemangioendotheliomas are vascular lesions of the liver that usually present in the infant with hepatomegaly, high output congestive heart failure and cutaneous hemangiomas. The diagnosis, pathologic and physiologic conditions and treatment were discussed. Two of the patients we studied and 117 from the literature were reviewed. A total of 38 patients survived and 57 died with or without medical treatment. Thirteen patients survived and five died after ligation of the hepatic artery. Five patients survived and three died after embolization of the hepatic artery. (formula; see text) Of 119 patients with MHH, 81 (68 per cent) had congestive heart failure; 40 survived and 41 died. Of 56 patients with localized hepatic angiomas, 19 had congestive heart failure. Only two of the patients died of heart failure. Fifty localized hepatic angiomas in infancy that were treated with local resection or lobectomy were reviewed. Forty-six patients survived and four died of hemorrhage. Four patients survived and two died with or without medical treatment. Plans for management of multiple hepatic hemangioendotheliomas and localized hepatic angiomas in infancy were proposed.

Embolization, Therapeutic↗
PubMed1988

Peptide analogues compete with the binding of alpha-factor to its receptor in Saccharomyces cerevisiae.

alpha-Factor, a secreted tridecapeptide pheromone, is required for mating between the a- and alpha-haploid mating types of Saccharomyces cerevisiae. An analogue of alpha-factor, [DHP8,DHP11,Nle12] tridecapeptide (where DHP represents 3,4-dehydro-L-proline and Nle represents norleucine), was catalytically reduced in the presence of 3H gas to produce a radiolabeled pheromone with high specific activity, purity, and biological activity. Association and dissociation kinetics indicated values of 4.9 x 10(4) M-1 s-1 for k1 and 1.1 x 10(-3) s-1 for k-1. Saturation binding studies gave an equilibrium dissociation constant equal to 2.3 x 10(-8) M, which approximated the kinetically derived KD of 2.2 x 10(-8) M. These values compare favorably to the previously determined KD of 6 x 10(-9) M (Jenness, D.D., Burkholder, A.C., and Hartwell, L.H. (1986) Mol. Cell. Biol. 6, 318-320). Scatchard analysis and dissociation in the presence of excess unlabeled ligand indicated interaction with a homogeneous population of noninteracting binding sites (13,000 sites/cell). A number of alpha-factor analogues, previously investigated for their structure-function relationships (Naider, F., and Becker, J.M. (1986) CRC Crit. Rev. Biochem. 21, 225-249), were used to compete with [3H]alpha-factor binding. Four tridecapeptides having conservative amino acid replacements bound strongly to the receptor. In contrast, [Phe3]alpha-factor and 10 des-Trp1-alpha-factor analogues bound to the receptor 1-3 orders of magnitude less effectively than did alpha-factor itself. The binding constants for all active pheromones correlated with biological activity. However, des-Trp1[Phe3]alpha-factor and des-Trp1-[Ala3]alpha-factor, which were not biologically active, still competed with alpha-factor binding, indicating that these analogues fail to induce a secondary signal necessary for biological response to the pheromone. One analogue, des-Trp1-[Cha3,L-Ala9]alpha-factor (where Cha represents cyclohexylalanine), was not biologically active and did not demonstrate binding to the receptor, whereas des-Trp1-[Cha3,D-Ala9]alpha-factor was active and bound to the receptor. This finding suggests that a type II beta-turn is necessary for binding of alpha-factor to its receptor and for subsequent biological activity.

Binding, Competitive↗
PubMed1988

Guanine nucleotide regulation of adenylate cyclase in permeabilized cells of Saccharomyces cerevisiae.

Adenylate cyclase in permeabilized cells of Saccharomyces cerevisiae was examined. Among various permeabilization procedures, including organic solvents, detergents and other reagents, dimethylsulfoxide (DMSO) and digitonin treatments resulted in the highest recovery of adenylate cyclase activity. Incubation of cells at 30 degrees C with digitonin at 0.01% to 0.1%, or DMSO at 20% to 40% for 15 to 30 min gave optimal adenylate cyclase activity. The enzyme activity in digitonin-permeabilized cells could be supported only by Mn2+, whereas Mg2+ with or without guanine nucleotides did not support cyclase activity. DMSO-permeabilized cells exhibit efficient Mn2+- and Mg2+/Gpp[NH]p-dependent stimulation. Furthermore, digitonin added to yeast membranes at a 1:50 detergent to protein ratio (w/w) abolishes guanyl nucleotide regulation without significantly affecting the Mn2+-supported cyclase activity. The superiority of DMSO is further supported by the fact that recovery of adenylate cyclase activity is better in the DMSO-treated cells than in the digitonin-treated cells. DMSO most probably causes less disturbance of the fabric of the native cell. We conclude that digitonin, but not DMSO, uncouples the catalytic unit of adenylate cyclase from the regulatory GTP binding (ras) proteins.

Adenosine Triphosphate↗
PubMed1988

Experimental ileal J-pouch construction. A comparison of three techniques.

Endorectal ileal pouch-anal anastomosis has become the surgical alternative of choice for patients requiring colectomy for ulcerative colitis or familial polyposis coli. The optimal method of ileal pouch construction has not been determined. In this study, a canine preparation was used to compare the immediate results of three different techniques of ileal J-pouch construction. The three methods studied were two-layer hand-suturing (HS), stapling through enterotomies placed laterally on the ileal limbs (LS), and stapling via an apically placed enterotomy (AS). All three techniques resulted in watertight reservoirs. Ease of construction was scored significantly differently among the pouch variations (AS greater than LS greater than HS). Construction time was significantly less for both of the stapled reservoirs than for the HS pouch. Capacity of the AS pouch was significantly greater than the HS reservoir. This study suggests that stapling the ileal J-pouch through a single apical enterotomy should be the preferred technique during colectomy, mucosal proctectomy, and ileal pouch-anal anastomosis.

Anal Canal↗
PubMed1988

Postprandial sphincter of Oddi myoelectric activity and gallbladder emptying.

Feeding initiates gallbladder emptying and bile delivery into the duodenum. It is not yet defined how the sphincter of Oddi regulates flow of bile into the duodenum during gallbladder emptying. The aim of this study was to assess postprandial spike burst activity in the sphincter of Oddi, while quantitating gallbladder emptying with noninvasive radioisotope imaging. Six adult opossums were prepared with bipolar electrodes in the sphincter of Oddi. After 2 weeks of recovery the animals were fasted overnight and positioned under a gamma camera, and myoelectric recordings were begun. After two cycles of the migrating motor complex (MMC), 2 mCi 99Tc-HIDA was infused intravenously and permitted to concentrate in the gallbladder for a period of 30 min. Subsequently, a 30-ml liquid meal, containing 0.9 g protein, 3.5 g carbohydrate, and 3.3 g fat, was instilled into the stomach. Sphincter of Oddi myoelectric activity (spike bursts/min) and gallbladder emptying (expressed as percentage of original 99Tc counts in the gallbladder) were measured at intervals for 120 min following feeding. Feeding resulted in prompt gallbladder emptying. Sphincter of Oddi spike burst activity was not altered significantly in the first 30 min after feeding, suggesting that motor activity in the sphincter of Oddi does not initially influence bile flow. Subsequently, spike burst activity increased progressively, suggesting that sphincter of Oddi motor activity may accelerate bile delivery into the duodenum during later phases of gallbladder emptying.

Ampulla of Vater↗
PubMed1988

Synthesis and anticandidal properties of polyoxin L analogues containing alpha-amino fatty acids.

Analogues of polyoxin L containing amino acids with saturated fatty acid like side chains were synthesized from the benzyloxycarbonyl-protected alpha-amino fatty acid p-nitrophenyl ester and uracil polyoxin C. Transfer hydrogenolysis using palladium black and formic acid gave diastereomeric, dipeptidyl polyoxin L analogues containing alpha-aminooctanoic acid (3), alpha-aminododecanoic acid (4), or alpha-aminohexadecanoic acid (5) as the amine terminal residue in 40-60% yield. Diastereomers of 3 and 5 were resolved by using high-performance liquid chromatography on a reversed-phase column and designated as 3a, 3b and 5a, 5b. Analogues 3-5 were excellent inhibitors of chitin synthetase from Candida albicans; 4, the best inhibitor, had an ID50 of 0.5 microM. The L,L diastereomers of 3 and 5 were 1-2 orders of magnitude more potent chitin synthetase inhibitors than their D,L homologues. None of the synthetic polyoxin L analogues inhibited transport of trimethionine, but 3a, 4, and 5b caused decreases of 71%, 87%, and 83%, respectively, in the initial rate of uptake of dileucine. Compounds 3-5 were significantly more stable to peptidase degradation than polyoxin L analogues containing naturally occurring alpha-amino acids. Compound 4 inhibited growth of C. albicans in culture at 40-80 micrograms/mL. All other analogues were less potent antifungals. The results suggest that synthetic polyoxins can be designed to have increased affinity for a peptide transport system and to have increased stability against intracellular degradation in C. albicans.

Antifungal Agents↗
PubMed1988

Cefoxitin disposition in colorectal surgery. Implications for the effective use of prophylactic antibiotics.

Failure of antibiotic prophylaxis to prevent infectious complications following colorectal operations is reported to occur in 5 to 10% of all cases. Factors such as the length of surgery and inadequate antibacterial coverage or duration predispose patients to higher rates of infectious complications. The pharmacokinetics of cefoxitin in eight patients undergoing colectomy, mucosal proctectomy, and endorectal ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis or familial polyposis coli were examined. Peak plasma concentrations were 40% higher than values reported in healthy volunteers. During the first dose, the plasma half-life of cefoxitin was similar to plasma half-lives reported in healthy volunteers; however, total body clearance was reduced five- to eightfold. These data suggest that the volume of distribution of cefoxitin was also markedly reduced. Fluid replacement during the operation produced lower cefoxitin peak plasma concentrations after the second dose. Cefoxitin clearance increased during the second dose after fluid replacement, but remained below that reported in healthy volunteers. These data suggest that fluid depletion resulting in decreased kidney perfusion contributed to a reduction in drug clearance. The amount of cefoxitin recovered in the urine during the 12-hour study period averaged 53%. Tissue concentrations of cefoxitin in proximal colon, distal colon, rectal mucosa, and rectal muscle tissue ranged from 0.2 to 9.3 mcg/g of tissue. The preoperative fluid status of the patient, the time of drug administration, and the amount of extra-renal drug elimination appear to be important factors, affecting the disposition of parenterally administered prophylactic antibiotics in patients undergoing colorectal operations.

Adenomatous Polyposis Coli↗
PubMed1988

Catheter-associated Candida utilis fungemia in a patient with acquired immunodeficiency syndrome: species verification with a molecular probe.

Candida utilis was cultured from the blood of a patient with acquired immunodeficiency syndrome. The candidemia was apparently associated with catheter implantation. The isolate was identified initially by standard methods and verified by molecular probing. The pattern of actin-specific restriction fragments obtained from the DNA of the isolate, probed with C. albicans actin sequences, corresponded to that of C. utilis. This organism adds to the growing list of Candida species associated with human disease. Molecular probing offers a definitive identification when an unexpected etiological agent is found.

Acquired Immunodeficiency Syndrome↗
PubMed1988

A stapled technique for construction of ileal J pouches.

A new technique of ileal pouch construction for patients undergoing colectomy, mucosal proctectomy and endorectal ileal pouch to anal anastomosis for chronic ulcerative colitis or familial polyposis coli is reported. The simple stapling technique, whereby a linear stapler is repeatedly fired through a single apical enterotomy can be performed rapidly and safely and facilitates subsequent anastomosis of the ileal J pouch to the anus.

Adenomatous Polyposis Coli↗
PubMed1988

Duodenal polyposis and malignancy in a case of familial polyposis coli.

Familial polyposis coli is characterized by progressive adenomatosis with ultimate progression to colon cancer. It is becoming clear that these patients also have a high incidence of upper gastrointestinal adenomatous polyps, with some developing periampullary malignancies similar to those seen in Gardner's syndrome. This has led to recommendations for periodic endoscopic screening of asymptomatic polyposis patients. We report a patient with familial polyposis coli who developed an adenocarcinoma in the distal duodenum. This case points out the importance of screening the upper gastrointestinal tract in patients at risk.

Adenocarcinoma↗
PubMed1988

Emergencies in inflammatory bowel disease.

A review of acute emergencies in inflammatory bowel disease is presented. Caveats include prompt surgical drainage of loculated abscesses and aggressive management of bleeding or perforation. Adequate nutritional and immunologic assessment of all patients prior to surgery is paramount and has resulted in the widespread use of total parenteral nutrition. Aggressive medical therapy, particularly steroids, may be useful in "cooling down" cases of acute inflammation prior to surgery. This is particularly useful in Crohn's disease, in which recurrences abound and surgery has a significant degree of complication and recurrence. When urgent operation is necessary for acute ulcerative colitis, abdominal colectomy with ileostomy and preservation of the rectum is generally indicated. This will allow subsequent mucosal proctectomy and ileoanal anastomosis. When urgent colectomy is indicated for Crohn's colitis without rectal involvement, ileorectal anastomosis can be considered either as a primary or secondary procedure. If toxic megacolon is present, an initial trial of medical therapy is warranted in order to allow a single-staged operation to be performed electively.

Colitis, Ulcerative↗
PubMed1988

Graded effect of protein on regional myoelectric activity of the opossum sphincter of Oddi.

Although it is known that the sphincter of Oddi exhibits a myoelectric response to intraluminal nutrients, the effect of specific dietary components has not been well characterized. The aim of this study was to determine the effect of intragastric instillation of a protein meal on regional myoelectric activity of the opossum sphincter of Oddi. Seven adult opossums were chronically prepared with self-retaining bipolar electrodes secured to the proximal and distal parts of the sphincter. After a 2-week recovery period, and with the animals fasted and conscious, myoelectric activity was recorded for two cycles of the migrating myoelectric complex. The animals then received graded calories of protein through an orogastric tube and recordings were continued until return of the fasted cyclic activity. Doses of 60, 120, and 240 kcal of protein elicited increases in myoelectric spike activity of the proximal sphincter of 18.7%, 41.9%, and 66.6%, respectively. Similarly, the length of the fed state was prolonged by increasing caloric loads, with mean (plus or minus standard error of the mean) times of 266 +/- 25, 292 +/- 15, and 375 +/- 42 minutes for each dose. A similar relationship was noted in the distal part of the sphincter. Regression analysis between the proximal and distal parts of the sphincter during the fasted and fed states showed a strong and persistent correlation of gradient of spikeburst frequency. We conclude that myoelectric spike frequency of the opossum sphincter of Oddi exhibits a dose-related response to intragastric protein calories. Furthermore, the proximal and distal parts of the sphincter remain electrically coupled, with the proximal region pacing the distal region during the fasted state and after protein administration.

Ampulla of Vater↗
PubMed1987

Synthesis and biological activity of amino terminus extended analogues of the alpha mating factor of Saccharomyces cerevisiae.

The synthesis and biological activity are reported for extended analogues of the secreted tridecapeptide alpha-factor (Trp-His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr) from Saccharomyces cerevisiae. Peptides with Ala, Glu-Ala, Ala-Glu-Ala, or Glu-Ala-Glu-Ala attached to the amino terminus of alpha-factor were synthesized by the solid-phase method on a (phenylacetamido)methyl (PAM) resin, using a combination of dicyclohexylcarbodiimide- and 1-hydroxybenzotriazole-accelerated active ester coupling procedures. Free peptides were obtained by hydrogen fluoride (HF) cleavage in the presence of appropriate scavengers. Normal high HF cleavage and "low-high" HF cleavage were equally effective in liberating the desired product from the PAM resin. Yields of pure peptide ranged from 9% to 17%. All of the extended alpha-factors, which represent sequences of pro-alpha-factor coded for in the MF alpha 1 structural gene, caused morphological aberrations (shmoo assay) in strain X2180-1A (MATa) the same as those caused by the tridecapeptide. The 14-peptide was equally active compared to the native alpha-factor whereas the 17-peptide was 5-10-fold less active. The analogues also arrested to various degrees (halo assay) the growth of S. cerevisiae RC629 (MATa sst1) and S. cerevisiae RC631 (MATa sst2), two supersensitive mutants, and were converted to pheromones of equal activity by treatment with V8 protease. A temperature-sensitive receptor mutant responded to all the peptides at the permissive but not the restrictive temperature. An alpha-factor antagonist, des-Trp1,Ala3-alpha-factor, inhibited activity of all extended peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1987

Enhanced killing of Candida albicans by murine macrophages treated with macrophage colony-stimulating factor: evidence for augmented expression of mannose receptors.

The effect of macrophage colony-stimulating factor (CSF-1) on killing of Candida albicans by murine peritoneal macrophages was determined. The killing capacity of resident peritoneal macrophages was unaffected by CSF-1. However, proteose-peptone-elicited peritoneal exudate macrophages that had been pretreated with CSF-1 (greater than or equal to 1000 U/ml) for 24 or 48 hr exhibited a significantly enhanced capacity to kill C. albicans. CSF-enhanced killing appeared to be independent of endogenously produced interferon-alpha/beta (IFN) in that enhancement by these two agents differed with regard to onset of the effect, target cell responsiveness, and duration of augmented killing. In addition, a highly specific anti-IFN antiserum that totally neutralized IFN augmentation of candidacidal activity had no effect on CSF-induced enhancement. Evidence was obtained indicating that CSF, unlike IFN, augmented mannose-inhibitable binding and ingestion of C. albicans, suggesting that augmented expression of mannose-receptors by CSF-treated macrophages was at least partially responsible for the enhanced killing.

Animals↗