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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 343 records · Page 19Linked to original sources

Role of the protease-antiprotease balance in peritoneal exudate during acute pancreatitis.

The peritoneal exudate formed during experimental pancreatitis is toxic when administered intraperitoneally or intravenously to other animals. Overwhelming of the peritoneal antiprotease defences by proteolytic enzymes released from the pancreas may be a key factor responsible for this toxicity and is examined in the current study. Human pancreatitis exudates possessed tryptic amidase activity indicating trypsinogen activation. The trypsin inhibitory capacities of exudates were reduced indicating a degree of consumption of the peritoneal antiproteases. Of 21 exudates examined, three showed marked reduction of their trypsin inhibitory capacity indicating almost complete consumption of their antiproteases. All three patients were shocked at the time of sampling, two dying of fulminant pancreatitis within 24 h. Overwhelming of the peritoneal antiproteases was not confirmed, but may occur in a few instances where proteolytic enzyme release or zymogen activation continues. Intraperitoneal administration of exogenous antiproteases prolongs survival in rats with pancreatitis and has been suggested as a therapy in man. The current data suggests that few patients are likely to benefit from such an approach.

Acute Disease↗

Distribution of mitochondrial r1-type introns and the associated open reading frame in the yeast genus Kluyveromyces.

We have sequenced the intron in the large subunit ribosomal RNA gene from the mitochondrion of Kluyveromyces lactis. It is a typical group I intron but, unlike the corresponding intron (r1) in Saccharomyces cerevisiae, it does not contain an open reading frame. This intron is widespread in the genus Kluyveromyces although intron-less strains were also found in some species of this genus. Sequences homologous to the open reading frame of the S. cerevisiae ribosomal intron were detected in some strains of K. waltii, K. thermotolerans and K. africanus.

Base Sequence↗

Platelet activating factor as a proinflammatory mediator in acetic-induced colitis in the rat.

Platelet activating factor (PAF) induces neutrophilia and produces a variety of gastrointestinal lesions. The role of PAF as a proinflammatory mediator was examined by measuring the production of PAF and the efficacy of the PAF antagonists WEB 2086 and Ro 24-0238 in acetic acid (HOAc)-induced colitis. PAF levels within the colonic mucosa, as measured by radioimmunoassay, increased from 259 +/- 119 ng/mg in control tissue, to 616 +/- 266 ng/mg in HOAc inflamed tissue. The accumulation of neutrophils within the mucosa was decreased by 53 +/- 10% by pretreatment with 3 mg/kg WEB 2086, and by 43 +/- 11% by 3 mg/kg Ro 24-0238. PAF-induced neutrophilia had no effect on the severity of HOAc-induced colitis, therefore, PAF my be involved in sustaining the chronic inflammation of colitis.

Acetates↗

Identification of target genes of the homeotic gene Antennapedia by enhancer detection.

Localized expression of the homeotic gene Antennapedia (Antp) in Drosophila melanogaster is required for normal development of the thoracic segments. When the Antp gene is expressed ectopically in the larval primordium of the antenna, the antennal imaginal disc, the developmental fate of the disc is switched and the adult antenna is transformed to a mesothoracic leg. We screened approximately 550 different fly strains carrying single copies of an enhancer-detector transposon to identify regulatory elements and corresponding genes that are either activated or repressed in antennal discs in response to this transformation. Several regulatory elements that are either direct or indirect targets of Antp were found. One transposant that expresses the reporter gene (lacZ) in the antennal disc, but not in the leg disc, was studied in more detail. The enhancer detector in this strain is located near a similarly regulated gene at the spalt (sal) locus, which encodes a homeotic function involved in embryonic head and tail development. The expression of this newly discovered gene, spalt major (salm) is strongly repressed in gain-of-function mutants that express Antp in the antennal disc. Recessive loss-of-function mutations (Antp-) have the opposite developmental effect; they cause the differentiation of antennal structures in the second leg disc. Accordingly, salm is derepressed in clones of homozygous Antp- cells. Therefore, we conclude that Antp negatively regulates salm. The time course of the interaction and reporter gene fusion experiments suggests (but does not prove) a direct interaction between Antp and cis-regulatory elements of salm. Our analysis of several enhancer-detector strains suggests that the basic patterning information in the antennal and leg imaginal discs is very similar.

Alleles↗

Metastatic renal clear cell carcinoma in the thyroid gland diagnosed by fine needle aspiration cytology.

An 81-year-old woman presented with a mass in the right lobe of the thyroid. Fine needle aspiration of this lesion showed metastatic clear cell carcinoma. This was subsequently confirmed histologically. In patients with metastatic carcinoma, tumour deposits are frequently found in the thyroid. The most common metastatic tumour to masquerade as a primary thyroid tumour is a renal cell carcinoma. In patients with this tumour the possibility that a thyroid mass may be a metastatic deposit should always be considered.

Aged↗

Construction and properties of retrovirus packaging cells based on gibbon ape leukemia virus.

We have constructed hybrid retrovirus packaging cell lines that express the gibbon ape leukemia virus env and the Moloney murine leukemia virus gag-pol proteins. These cells were used to produce a retrovirus vector at over 10(6) CFU/ml, with a host range that included rat, hamster, bovine, cat, dog, monkey, and human cells. The gag-pol and env expression plasmids were separately transfected to reduce the potential for helper virus production, which was not observed. The NIH 3T3 mouse cells from which the packaging lines were made are not infectable by gibbon ape leukemia virus; thus, the generation and spread of possible recombinant viruses in the packaging cells is greatly reduced. These simian virus-based packaging cells extend the host range of currently available murine and avian packaging cells and should be useful for efficient gene transfer into higher mammals.

Animals↗

Current concepts in the management of pancreatitis.

Acute pancreatitis is often a mild, self-limiting illness that responds to simple supportive therapy in the form of intravenous fluids and analgesics. More severe attacks may result in organ failure or pancreatic necrosis. Such patients should be identified early in the course of an attack and actively monitored within an intensive care unit or high dependency area. Supportive therapy remains the basis of management. Attention to the adequacy of the fluid balance and oxygenation are of prime importance and supportive therapy may include inotropic support, assisted ventilation and renal dialysis. Pancreatic necrosis should be sought by contrast-enhanced computed tomography (CT) scanning, and surgical intervention may be required if the patient's clinical condition continues to deteriorate. Surgery should ideally be delayed until the second or subsequent week when necrosectomy (debridement of necrotic pancreatic tissue) may be possible rather than formal pancreatic resection. The role of various drugs to suppress pancreatic secretion and inhibit pancreatic enzymes, although shown to be consistently effective in experimental pancreatitis, has not been established by controlled clinical trials in humans. Recent controlled studies examining peritoneal lavage in humans have failed to confirm the beneficial results suggested in earlier studies. Early endoscopic sphincterotomy for patients with severe gallstone pancreatitis and ductal calculi has been reported to reduce mortality and morbidity in one controlled clinical trial and may prove to be an important advance.

Acute Disease↗

Effects of ginkgolide B, a platelet-activating factor inhibitor on insulitis in the spontaneously diabetic BB rat.

The BB rat spontaneously develops insulin-dependent diabetes mellitus (IDDM) in association with marked insulitis in the islet of Langerhans. Since platelet-activating factor (PAF-acether) is involved in allergic and inflammatory reactions, we tested a PAF antagonist, Ginkgolide B (BN 52021) for potential effects on islet inflammation and diabetes. Diabetes prone BB/Wor rats were treated daily from weaning at 25 days until 105 days of age with either saline (n = 30, controls), 10 (n = 25, low dose) or 20 (n = 30, high dose) mg/kg body weight of BN 52021. The overall incidence of IDDM was unaffected by treatment. Quantitative analysis of insulin area showed a dose-dependent protection of beta cells by Ginkgolide B, reflected in a 6- (low dose) to 8-fold (high dose) (P less than 0.01-0.005) increase in the insulin/glucagon cell ratio compared to the saline treated rats. Ginkgolide B reduced severe insulitis from 84% in the saline rats developing IDDM to 59% (n.s.) in the low and to 33% (P less than 0.001) in the high dose group. These data suggest that PAF inhibitors may prove useful in immunomodulator therapy of IDDM since beta cells are preserved.

Animals↗

Measurement of testicular blood flow at orchiopexy with a solid state laser.

We have evaluated the solid state laser as a means of determining testicular blood flow at operation. A solid state laser was used to measure blood flow before mobilization of cryptorchid testes, and subsequently after mobilization and placement within a subcutaneous scrotal pouch. Testicular volume was calculated. The median blood flow (ml/100 gm/min) before mobilization was 8.96 (range, 3.43 to 27.2). After mobilization a modest rise to 9.39 (range, 1.82 to 23.75) occurred, which was not statistically significant. However, heterogeneity existed in the response; 11 testes showed a median fall of 8.07 (range, 1.59 to 15.36), which was significant compared to the initial value; 16 testes showed a variable degree of hyperemia with a rise of 2.57 (range, 0.1 to 12.7), which was also significant compared to the initial value; two testes showed no change. The testes that showed a fall in blood flow were all high abdominal testes, which required the most mobilization. The mean testicular volume was 0.38 cc (SEM, 0.03 cc). No difference was noted in size between testes with a net rise in blood flow (mean volume, 0.38 cc) and testes with a net fall in blood flow (mean volume, 0.375 cc). No relationship was noted between testicular size and blood flow. We conclude that the solid state laser is a simple means of measuring testicular blood flow at orchiopexy and may provide a method of deciding which testes should undergo microvascular replantation on the basis of inadequate perfusion per-operatively.

Cryptorchidism↗

Successful treatment of disseminated Fusarium infection after autologous bone marrow transplantation for acute myeloid leukemia.

Disseminated Fusarium is a rare but life-threatening infection of severely immunocompromised patients. A fatal outcome has been described in all reported cases of Fusarium infection occurring after bone marrow transplantation. We describe a patient who developed disseminated Fusarium infection with a secondary fungal endophthalmitis after an autologous bone marrow transplant for acute myeloid leukemia. This infection was successfully eradicated after neutrophil recovery by prolonged systemic administration of amphotericin B as well as aggressive local therapy including enucleation of the affected eye. The patient remains free of both leukemia and fungal disease more than 4 years after transplant.

Adult↗

Trypsinogen activation peptides assay in the early prediction of severity of acute pancreatitis.

Trypsinogen activation can be quantified by measurement of released activation peptides (TAP assay). TAP assay in urine was performed on admission for 55 patients with acute pancreatitis. TAP concentration correlated with subsequent disease severity in 87%, whereas C-reactive protein concentration, and multifactorial scoring at 48 h, were correct in 55% and 84%. Sensitivity and specificity for TAP assay were 80% and 90%, for C-reactive protein 53% and 55%, and for multifactorial scoring at 48 h, 60% and 93%. Urine TAP assay distinguishes acute pancreatitis without trypsinogen activation from acute pancreatitis with trypsinogen activation, and helps to identify patients who will progress to the severe acute disease. Use of the assay should allow early intensive treatment of those who need it.

Acute Disease↗