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Biomedical subjects

K J Watson

Publications and source records attributed to K J Watson.

12 recordsLinked to original sources
PubMed2025

The UTRs of Leishmania donovani vary in length and are enriched in potential regulatory structures.

Leishmania spp. regulate gene expression largely post-transcriptionally, yet untranslated regions (UTRs) remain poorly delineated. We generated high-quality genome and transcriptome datasets for Leishmania donovani strain 1S2D (Ld1S) by combining PacBio HiFi de novo assembly with Oxford Nanopore direct RNA sequencing of promastigotes and axenic amastigotes. The genome assembly consists of 65 scaffolds totaling ~33.3 Mb. Structural comparisons to LdBPK282A1 revealed numerous rearrangements, including some reshuffling genes among polycistronic transcription units and validated by polycistronic reads from RNA sequencing. Promastigote and amastigote RNA sequencing produced 469,010 and 46,729 monocistronic reads containing a spliced-leader and a polyA tail sequences, defining 8,479 transcripts and supporting 7,415 of the 7,969 annotated protein coding genes, as well as 604 putative long non-coding RNAs. We annotated UTRs for 4,921 genes and observed that putative RNA G-quadruplexes were markedly enriched in UTRs. We also noted that 31.9% and 11.5% were expressed into multiple isoforms in promastigotes and amastigotes, respectively. Collectively, these data provide a comprehensive annotation of L. donovani genes and their UTRs and reveal widespread and stage-specific UTR length polymorphisms, and, overall, points to an important role of 3' UTR in post-transcriptional regulation in L. donovani.

Journal Article↗
PubMed1990

Spontaneous paracentesis following rupture of an umbilical hernia.

Spontaneous paracentesis following a ruptured umbilical hernia is a rare but dramatic event. Only 58 cases have been recorded in the English language literature. We describe here the management and successful outcome of one such case with documented substantial paracentesis of approximately 11 L.

Ascites↗
PubMed1989

Hepatic extraction of morphine is impaired in cirrhosis.

Using hepatic vein catheterization this study has provided the first direct measurement of morphine hepatic extraction in 8 controls and 8 cirrhotics. The extraction ratio was 0.52 in the control group and was reduced by 25% in the cirrhotics. This reduction is due to impaired enzyme capacity rather than reduced blood flow. The effect of cirrhosis is less than that reported in similar studies of high clearance oxidized drugs and this lends support to the concept that glucuronidation may be relatively spared in cirrhosis. A discrepancy between the systemic clearance and the hepatic clearance provides indirect support for extra-hepatic metabolism of morphine.

Adult↗
PubMed1989

Gilbert's syndrome.

While Gilbert's syndrome is extremely common and benign, its pathogenesis may not be as straightforward as once believed. It has been used as a model to examine aberrations of virtually every step in bilirubin metabolism. The clinical hallmarks are of a hereditary, chronic, mild unconjugated hyperbilirubinaemia. Not infrequently subclinical haemolysis may coexist. Liver histology is normal although some minor ultrastructural abnormalities may be evident. The universal defect appears to be a reduction in hepatic bilirubin-GT activity. However, other associated abnormalities in bilirubin metabolism, which occur less consistently, suggest that this may not be the sole defect in all patients. The syndrome is almost certainly part of a spectrum which includes the Crigler-Najjar syndromes; molecular biology data suggests that there is an absence of one (or even more) GT isoenzymes in these disorders. Whether one or more genes is consistently culpable remains open to speculation. Despite the complicated pathogenesis of Gilbert's syndrome, management remains simply reassurance alone.

Age Factors↗
PubMed1986

Metoclopramide--a review.

Metoclopramide has wide applications in both clinical and experimental medicine. It is useful in the management of gastro-oesophageal reflux and gastric stasis. It is being used increasingly in the management of nausea and vomiting, and at high doses will significantly relieve the emesis that is induced by cytotoxic agents. Metoclopramide also has an important place in the investigation of the role of dopamine in physiological and pathological processes.

Anxiety↗
PubMed1986

The effects of age and chronic liver disease on the elimination of temazepam.

The pharmacokinetics of the newer 1, 4 benzodiazepine temazepam were evaluated in 16 healthy subjects aged 18-92 years and in 15 cirrhotic patients, to ascertain the effect of ageing and liver disease. The data were analysed both by classic two compartment and by non-compartmental methods. The mean elimination half-life in the control subjects was 15.5 h, considerably longer than previous estimates. No correlation was found between age and pharmacokinetic parameters. The cirrhotic group showed no statistically significant difference in the pharmacokinetic parameters nor in the urinary recovery of the dose from the control group. Temazepam plasma protein binding was assessed in a second group of 9 cirrhotics of similar severity to the main group and in matched controls. When these binding data were applied to the mean clearance data, a modest although not statistically significant, reduction in free drug clearance was observed in the cirrhotic group. This study adds further support to the observation that drugs which undergo ether glucuronidation have normal elimination patterns in patients with liver disease. Temazepam may prove to be a useful hypnotic sedative in patients with liver disease.

Adult↗
PubMed1986

Hepatic vein occlusion (Budd-Chiari syndrome): problems in diagnosis and management.

Seven patients demonstrating the difficulties in diagnosis and management of hepatic vein occlusion are presented. The syndrome may present in an acute form with upper abdominal pain, abdominal swelling, ascites and tender hepatomegaly or in a chronic form, mimicking cirrhotic ascites. The clinical features, predisposing factors, liver scan and liver biopsy may all suggest the condition, but hepatic venography is essential for diagnosis and as a preliminary to treatment. It is suggested that early side to side portacaval anastomosis is the current treatment of choice.

Aged↗
PubMed1985

Watery diarrhea-hypokalemia-achlorhydria syndrome and carcinoma of the esophagus.

The watery diarrhea-hypokalemia-achlorhydria syndrome associated with ectopic secretion of vasoactive intestinal peptide has only been conclusively documented with tumors originating in the pancreas or sympathetic chain. We report here the case of a 50-yr-old woman who developed this syndrome 3 wk after an apparently effective course of radiotherapy for an obstructing, mixed-cell carcinoma of the esophagus. High concentrations of vasoactive intestinal peptide were found in plasma (100-200 pmol/L; normal less than 20 pmol/L) and in the metastatic skin nodules (750 pmol/g) that later developed and that contained one of the two cell types from the original tumor. Stool volumes reached a plateau of 15-20 L/day, and potassium requirements were greater than 1000 mmol/day. Symptoms failed to respond to any of the regimens previously described as effective in this syndrome. After 14 wk of massive fecal fluid and electrolyte losses, symptoms resolved dramatically with the first dose of 5-fluorouracil. Plasma vasoactive intestinal peptide concentration returned to normal, where it remained despite subsequent evidence of renewed tumor spread. This case illustrates the unpredictability of the response of this syndrome to medical treatment, and suggests that vasoactive intestinal peptide secretion may occur in a wider range of tumors than has so far been described.

Achlorhydria↗