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Biomedical subjects

J Perrault

Publications and source records attributed to J Perrault.

At least 73 records · Page 4Linked to original sources

D-Lactic acidosis and encephalopathy after jejunoileostomy: response to overfeeding and to fasting in humans.

Two patients with recurring attacks of encephalopathy after jejunoileostomy for morbid obesity had elevated D-lactate concentrations in blood and urine. The syndrome and the biochemical abnormalities were reproduced by ingestion of a high carbohydrate diet. In the second case, fasting and intravenous supplementation with amino acids and glucose resulted in the disappearance of D-lactate from the urine and blood and amelioration of the symptoms. Stool cultures from the second patient were shown to be capable of producing D-lactate, and concentrations of D-lactate in saline and peptone yeast broth filtrates of the stool paralleled the changes in urinary excretion of the D-lactate during fasting and overfeeding. Thus, we have demonstrated a temporal relationship between the neurologic symptoms and the elevated concentrations of D-lactate in blood, urine, and stool. Whether D-lactate accounts for part or all of the encephalopathic changes remains to be determined.

Acidosis↗

ATP dependence of vesicular stomatitis virus transcription initiation and modulation by mutation in the nucleocapsid protein.

We recently reported that vesicular stomatitis virus pol R mutants contain a template-associated N-protein alteration which allows for efficient readthrough of leader RNA termination sites in vitro (Perrault et al., Cell 35:175-185, 1983). We show here that in vitro RNA synthesis mediated by pol R virions is much more resistant to replacement of ATP by the analog beta,gamma-imido ATP than by wild-type virus (approximately 50% inhibition versus approximately 95%). Characterization of beta,gamma-imido ATP-resistant and control products by size, polyadenylic acid content, frequency of initiation at the 3' end of the template, and readthrough of the leader-N gene junction leads us to conclude the following: (i) most likely, the ATP dependence of the transcription process primarily reflects a requirement for initiation or entry of the polymerase at the 3' end of the template; (ii) this requirement is largely bypassed in the mutant pol R viruses; (iii) the synthesis of small, internally initiated transcripts by wild-type virus is less dependent on ATP than that of leader RNA; and (iv) termination at leader RNA sites is not directly affected when beta,gamma-imido ATP is added before initiation of synthesis. These results are discussed in terms of the possible roles of ATP and the nucleocapsid protein in initiation and termination of vesicular stomatitis virus RNA synthesis.

Adenosine Triphosphate↗

Fate of the rectal mucosa after rectal mucosectomy and ileoanal anastomosis.

The aim of our study was to determine if the rectal mucosa regenerates after rectal mucosectomy and endorectal ileoanal anastomosis for chronic ulcerative colitis. Such regenerated rectal mucosa could be the site of recurrent disease, leading to complications of the operation, and potential malignant degeneration. Pathologic specimens of the ileoanal anastomosis, surrounded by rectal muscular cuff, were obtained from eight patients who required takedown of their ileoanal anastomosis between one and 18 months after construction. Reepithelialization of the rectal cuff was not observed. In two patients, small islets of rectal mucosa and anal glands were identified. In all patients, the rectal muscularis propria was adherent to the serosa of the ileum by fibrous reaction. Three patients were diagnosed, both clinically and pathologically, as having chronic ulcerative colitis at the original ileoanal operation, but features suggestive of Crohn's disease were noted in the subsequently resected neo-rectum. Our observations suggest that, although isolated rectal mucosal cells may remain after mucosectomy, extensive rectal mucosal regeneration does not occur, thus minimizing the risk of recurrent disease and potential malignant change. Failure of an ileoanal anastomosis is therefore most likely related either to technical factors or to the presence of unsuspected Crohn's disease.

Adolescent↗

RNP template of vesicular stomatitis virus regulates transcription and replication functions.

Small leader RNAs, copied from the extreme 3' ends of the minus and plus strands of the vesicular stomatitis virus (VSV) genome, are thought to play a central role in the regulation of viral transcription and replication. We describe here a novel class of VSV mutants, denoted pol R, in which termination at leader sites in vitro is specifically suppressed. We have assayed for the presence of leader RNAs and readthrough transcripts in reaction products from standard virion templates (plus leader) and defective interfering particle templates (minus leader). In both cases, mutant virions gave rise to a much higher proportion of readthrough transcripts than wild type (greater than 80% vs approximately 10%). Reconstitution experiments with separated ribonucleoprotein (RNP) templates and polymerase protein fractions revealed, surprisingly, that the N protein moiety of the RNP template was responsible for readthrough. This conclusion was further supported by protein analyses that showed a similar charge change in the N protein of two independently isolated pol R VSV mutants. These results lead us to propose that modification of the N protein may regulate termination at leader RNA sites.

Defective Viruses↗

Sequence signal involved in the generation of an internally deleted defective interfering RNA from vesicular stomatitis virus.

We have determined the nucleotide sequence at the 3' end of the vesicular stomatitis virus (VSV) polymerase or L gene and compared it to that obtained from a defective interfering particle (DI) RNA generated by this virus. The latter (DI 0.50) contains a large internal deletion within this gene. The deletion begins exactly 253 residues from the transcription start of the gene and extends to approximately 300 bases from the 5' end of the standard RNA genome. The flanking sequences bear no homology to the eukaryotic consensus splice sequence. The sequence immediately preceding the deletion is complementary to the ribosome binding site of the L gene transcript and also resembles genome transcription termination sites. In addition, we present the results of nuclease protection experiments which show that this DI RNA retains an exact copy of the 3' end half of the standard genome (leader, N, NS, M and G genes), although its own 3' end is non-genomic. The implications of these findings regarding mechanisms of DI generation are discussed.

Amino Acid Sequence↗

Physiologic aspects of continence after colectomy, mucosal proctectomy, and endorectal ileo-anal anastomosis.

We examined the physiology of continence in 12 patients at least four months after colectomy, mucosal proctectomy, and endorectal ileo-anal anastomosis for ulcerative colitis and familial polyposis. The mean fecal output (+/-SEM) was 598 +/- 60 gm, passed as 12 +/- 4 movements/24 hr, of which 4 +/- 1 were passed at night. The patients were generally continent during the day and could distinguish gas from stool, but 11 of 12 leaked stools at night. Anal sphincter resting pressures (71 +/- 8 cm H2O) and squeeze pressures (171 +/- 15 cm H2O) of patients were similar to those of ten healthy controls (P greater than 0.05), although the rectal inhibitory reflex was absent in the patients. After operation, the distal bowel had a pressure-volume curve of greater slope (0.15 +/- 0.05 ml/cm H2O) than it had in controls (0.07 +/- 0.01 ml/cm H2O, P less than 0.05) and a lesser maximum capacity (patients, 248 +/- 31 ml; controls, 406 +/- 26 ml; P less than 0.05). The greater the capacity of the neorectum, the fewer was the number of bowel movements/day (r = 0.91, P less than 0.001). We concluded that the operation preserved the anal sphincter, although it decreased the capacity and compliance of the distal bowel and impaired continence.

Adult↗

Use of subcutaneous deferoxamine in a child with hemochromatosis associated with congenital dyserythropoietic anemia, type I.

A 12-year-old girl with congenital dyserythropoietic anemia, type I, was diagnosed as having hemochromatosis. Deferoxamine was given subcutaneously for 14 months. Iron overload, as measured by liver iron and serum ferritin levels, was reduced substantially, liver function tests improved, and hepatomegaly decreased. Toxicity was negligible.

Anemia, Dyserythropoietic, Congenital↗

Colectomy with rectal mucosectomy and ileoanal anastomosis in young patients. Its use for ulcerative colitis and familial polyposis.

Twenty-five children and young adults underwent colectomy with rectal mucosectomy and ileoanal anastomosis for chronic ulcerative colitis or familial polyposis. Follow-up ranged from three to 35 months. A simpler and shorter modification of the operation was used in 12 patients. Balloon catheter dilations were performed in nine patients before closure of the ileostomy to begin enlargement of the neorectum; 24 patients underwent closure of their temporary ileostomy. All patients are alive and well and participate full time in school or work. Two patients had mechanical bowel obstruction; on critical retrospective review, one patient was found to have Crohn's disease that necessitated removal of the rectal cuff. The clinical result was considered excellent in 11 patients, good in seven, fair in three, and poor in three. A gradual decrease in frequency of stooling was observed as the neorectum enlarged during the first year postoperatively. All patients had very good anal sphincter tone with voluntary rectal continence. Although some soiling and leakage occurred, especially during sleeping, these complications decreased with time.

Adolescent↗

Early development of the neorectum by balloon dilations after ileoanal anastomosis.

Recently, young people with chronic ulcerative colitis and familial polyposis have been undergoing colectomy with rectal mucosectomy and ileoanal anastomosis with encouraging clinical results. However, during the early period after closing the temporary ileostomy, some patients have frequent stools, which decrease with time as the terminal ileum dilates and becomes a reservoir. To enhance the early development of the neorectal reservoir and to minimize the frequent stooling, we instituted balloon dilations of the neorectum before ileostomy closure. A group of 16 patients not undergoing balloon dilations were compared with a similar group of 13 patients who had balloon dilations. Patients undergoing balloon dilations were observed to have an increase of 40.6% per month in the measured volume of the neorectum, along with a decrease of approximately 40% in the mean number of stools at 3 mo and 34% at 6 mo, with a very acceptable clinical result.

Adolescent↗

Surgical treatment of ulcerative colitis in children.

Our finding in 100 patients indicate that elective surgical treatment of ulcerative colitis in children has a low mortality rate in contrast to emergency surgery (2.3% versus 23%). Morbidity associated with these procedures is moderate and appears to be decreasing (13%), as shown by the comparison between the experience in the 1960s and that in the 1970s. Results with the newer surgical procedures have been encouraging; 60% of patients with Brooke ileostomy have been very satisfied as compared with 90% of patients with Kock pouch and of those with rectal mucosectomy with ileoanal anastomosis. Ileorectostomy was not a satisfactory procedure in this series. Additionally, after surgical treatment, the median height percentile increased from the thirty-ninth to fifty-seventh percentile. Finally, and important, 96% of the patients in this series reported that their general health at follow-up was good to excellent and that they had minimal limitation in their activities.

Adolescent↗

Campylobacter fetus ss. jejuni: a cause of massive lower gastrointestinal hemorrhage.

A patient is described with Campylobacter enteritis complicated by massive lower gastrointestinal bleeding from multiple mucosal ulcers in the terminal ileum and at the ileocecal valve. Repeated stool cultures and antibiotic therapy may be indicated in certain patients to diminish the morbidity arising from what may seem to be mild disease. In patients who suffer bleeding complications, arteriography before surgery is necessary to demonstrate an otherwise grossly indefinable source of bleeding.

Adult↗