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Biomedical subjects

J H Thomas

Publications and source records attributed to J H Thomas.

At least 91 records · Page 5Linked to original sources

Cell interactions coordinate the development of the C. elegans egg-laying system.

Egg laying by the nematode Caenorhabditis elegans requires the functioning of the vulva, the gonad, the egg-laying muscles, and the two HSN neurons, which innervate these muscles. By analyzing a newly isolated mutant (dig-1) that displaces the gonad, we discovered that cell interactions coordinate the spatial relationships among the different components of the egg-laying system. First, the gonad induces the formation of the vulva, and vulval induction by dorsal gonads strongly suggests that the inductive signal can act at a distance. Second, the gonad acts at a distance to regulate the migrations of the sex myoblasts that generate the egg-laying musculature. Third, the positions of the axonal branch and synapses of each HSN neuron are displaced correspondingly with the rest of the egg-laying system in dig-1 animals, which suggests that cell interactions also control aspects of HSN development.

Animals↗

Edgar J Poth lecture. Pathogenesis, diagnosis, and treatment of thrombosis.

Thrombosis and its major sequela, embolism, continue to contribute significantly to morbidity and mortality, both as primary disorders and as complications of other systemic systems. The understanding of the etiology of thromboembolism and the role of platelets, endothelium, and the plasma proteins in the development of thrombotic disorders has recently improved. Other blood cells, in particular neutrophils, have been suggested as possible mediators of thrombosis in clinical disorders characterized by decreased capillary blood flow. Newer imaging techniques such as duplex scanning have improved the accuracy and ease of diagnosis. Thrombolytic therapy is a more physiologic approach to the management of thrombosis, but its role is limited by systemic fibrinolysis. The development of fibrin-specific agents and better delivery techniques in combination with thromboembolectomy and anticoagulation should improve the management of patients with thrombosis.

Anticoagulants↗

Hemodynamics of the inferior mesenteric arterial circulation.

The purpose of this study was to determine the significance of collateral supply from the hypogastric arteries (HGAs) to the inferior mesenteric arterial (IMA) bed. Peak systolic "stump" IMA and radial arterial pressures were obtained before and after clamping the right HGA, the left HGA, both HGAs, the middle colic artery (MCA) only, or the MCA plus right HGA, MCA plus left HGA, and MCA plus both HGAs in patients with aortoiliac aneurysm or occlusive disease. Six patients (four with aneurysms and two with occlusive disease) had patent IMAs. Five patients (four with aneurysms and one with occlusive disease) had chronically occluded IMAs. In the six patients with patent IMAs, clamping of the HGAs decreased the IMA-stump pressure index (IMA-SPI) from 0.61 +/- 0.20 to 0.56 +/- 0.17, 0.54 +/- 0.17, and 0.54 +/- 0.19, respectively (p greater than 0.05) whereas clamping only the MCA decreased the IMA-SPI from 0.61 +/- 0.20 to 0.32 +/- 0.15 (p less than 0.01). In the five patients with chronically occluded IMAs, clamping of the HGAs decreased the IMA-SPI from 0.60 +/- 0.11 to 0.59 +/- 0.12, 0.58 +/- 0.12, and 0.57 +/- 0.11, respectively (p greater than 0.05), whereas clamping the MCA decreased the IMA-SPI from 0.60 +/- 0.11 to 0.34 +/- 0.04 (p less than 0.01). These data suggest that branches of the superior mesenteric artery provide the major collateral pathway to the IMA bed and that the contribution through branches of the HGAs is insignificant in the acute setting.

Aorta, Abdominal↗

Genetic analysis of defecation in Caenorhabditis elegans.

Defecation in the nematode Caenorhabditis elegans is achieved by a cyclical stereotyped motor program. The first step in each cycle is contraction of a set of posterior body muscles (pBoc), followed by contraction of a set of anterior body muscles (aBoc), and finally contraction of specialized anal muscles that open the anus and expel intestinal contents (Exp). By testing existing behavioral mutants and screening for new mutants that become constipated due to defects in defecation, I have identified 18 genes that are involved in defecation. Mutations in 16 of these genes affect specific parts of the motor program: mutations in two genes specifically affect the pBoc step; mutations in four genes affect the aBoc step; mutations in four genes affect the Exp step; and mutations in six genes affect both aBoc and Exp. Mutations in two other genes affect the defecation cycle period but have a normal motor program. Sensory inputs that regulate the cycle timing in the wild type are also described. On the basis of the phenotypes of the defecation mutants and of double mutants, I suggest a formal genetic pathway for the control of the defecation motor program.

Animals↗

Glomerular epithelial-cell endocytosis of horseradish peroxidase-polylysine conjugate in immune-complex glomerulonephritis.

Glomerulonephritis was induced in rats by daily intravenous cationised bovine serum albumin. The conjugate of horseradish peroxidase with poly-L-lysine was injected as a tracer of endocytosis by glomerular epithelial cells. The rats were sacrificed serially from 1 min to 24 h after the injection of the conjugate. The cytochemical localisation of peroxidase was observed by light- and electron-microscopy. Peroxidase was detectable in the GBM and immune deposits from 1 min after the injection but was cleared by 2 h. Cellular membrane staining by the conjugate and the membrane invaginations containing concentrated peroxidase were prominent adjacent to the subepithelial immune deposits. Peroxidase was initially localised intracellularly in membrane-bound vesicles adjacent to the subepithelial deposits. They subsequently moved towards the cell centre and became larger, some having the characteristics of lysosomes. Peroxidase activity significantly diminished within the cells by 16 h. The results show that glomerular epithelial-cell endocytosis in immune-complex glomerulonephritis is similar to that observed in the normal, but cellular membrane binding and invagination are more prominent adjacent to immune deposits. The trapping of the tracer in the deposits did not seem to alter its property of being taken up by the epithelial cells.

Animals↗

Pancreatogastrostomy: a safe drainage procedure after pancreatoduodenectomy.

The purpose of this study was to evaluate the role of pancreaticogastrostomy as an alternative method of restoring pancreaticointestinal continuity after pancreaticoduodenectomy. Since 1975, 45 patients have undergone pancreaticogastrostomy after pancreaticoduodenectomy at our institution. Pancreaticoduodenectomy was performed for pancreatic carcinoma (24 patients), ampullary carcinoma (8 patients), duodenal carcinoma (4 patients), common bile duct carcinoma (4 patients), pancreatic islet cell carcinoma (1 patient), trauma (1 patient), extensive colon carcinoma (1 patient), chronic pancreatitis (1 patient), and gastroduodenal artery aneurysm (1 patient). There was one operative death, for an overall operative mortality rate of 2%, and seven patients had major postoperative complications, for an overall morbidity rate of 15%. No pancreatic anastomotic leaks or other complications related to the pancreaticogastrostomy occurred. Twenty-four patients have died of recurrent carcinoma, with a mean survival of 25 months (range, 5 to 66 months), and 20 patients are alive and well, with a mean follow-up of 27 months (range, 2 to 106 months). Eight of these patients are alive 2 or more years after operation and four do not have exocrine pancreatic insufficiency. This experience confirms that pancreaticogastrostomy is a safe method of pancreatic drainage after pancreaticoduodenectomy and suggests that it may have technical advantages and therefore merits more widespread application.

Adult↗

Endocytosis of cationized horseradish peroxidase by glomerular epithelial cells is reduced in puromycin glomerulopathy.

Rats were treated with a single intravenous injection of aminonucleoside of puromycin and were sacrificed between 1 and 21 days after injection. The conjugate of horseradish peroxidase with a poly-L-lysine (HRP.PL) was used to reveal endocytotic activity in glomerular epithelial cells (GEC). This conjugate was injected intravenously 2 h before each sacrifice. Renal tissue was taken and treated cytochemically with a conventional DAB technique and observed by light and electron microscopy. The assessment of endocytosis by glomerular epithelial cells was performed on 1-micron sections by counting HRP.PL grains in the GEC and expressing this in terms of the area of glomerulus examined. The results were compared to those found in normal rats. Our results show that GEC endocytotic function was reduced during the whole period of the experiment. It fell quickly from 1 day after puromycin injection and reached the most marked reduction on the 4th day, preceding the peak of proteinuria which was between 7 and 12 days. From the 5th day onward the endocytotic function gradually recovered, but was still abnormal at the end of the experiment.

Animals↗

Cationization of bovine serum albumin alters its conformation as well as its charge.

The molecular charge on bovine serum albumin (BSA) was modified by substituting carboxyl groups on the protein with ethylenediamine, thereby producing a highly cationic derivative with a pI of 9.3 to 9.5. Gel-filtration studies showed that the molecular weight of BSA was not significantly altered after cationization. When the cationized BSA was administered to rabbits using a chronic serum sickness schedule of injections, the animals developed a membranous glomerulopathy similar to the human disease, except that approximately one-third of the animals also showed focal and segmental endocapillary proliferation. Comparison of the circular dichroism spectra of native and cationized BSA showed that the substitution of the carboxyl groups resulted in a 50% reduction in the alpha-helical content of the native molecule. This conformational change should be considered as a possible determinant of the different immune response and immunopathology associated with the cationized molecule compared with native BSA.

Animals↗

Endocytosis of horseradish peroxidase-poly-lysine conjugate by glomerular epithelial cells: an in vivo study.

Native horseradish peroxidase (HRP) is known to pass rapidly through glomeruli when injected into rats. We have found that a conjugate of HRP with poly-lysine is readily endocytosed by glomerular epithelial cells (GEC). We have used this conjugate to study the GEC endocytotic process in male Wistar rats. The conjugate has an approximate molecular weight of 55-58,000, a pI of greater than 10.0, and almost the same secondary conformation as HRP; it does not increase urinary protein excretion significantly or alter the morphology of the renal glomeruli. After intravenous injection of the conjugate, it could be found in the GBM from 1 min to 4 h. At 1 min, it was evenly distributed on GEC foot processes and plasma membrane. GEC start to take up the conjugate from 1 min post-injection, by cellular membrane invagination. This reached a maximum at 4 h. Some of the endocytosed conjugate passed to lysosomes from the endosomal system. The amount of peroxidase demonstrable in the glomerular epithelial cells was considerably reduced by 24 h.

Animals↗

Primary hypercoagulable states in general and vascular surgery.

Primary hypercoagulable states are increasingly recognized as causes of venous and arterial thromboembolism in surgical patients. Herein, we describe 10 patients with this syndrome who were diagnosed during a recent 1-year period. A family history and past medical history of thromboembolism and an unusual site of thrombosis are emphasized for accurate diagnosis. Although antithrombin III deficiencies were the most common abnormality found, we describe three patients with hypofibrinolytic syndromes and increased levels of tissue plasminogen activator inhibitor. The effectiveness of anticoagulation therapy in preventing recurrent thromboembolism is stressed.

Adolescent↗

Significance of tumor spread in adenocarcinoma of the ampulla of Vater.

Twenty-eight patients with ampullary carcinoma were treated between 1965 and 1988: 22 underwent pancreaticoduodenectomy with 1 operative death (5 percent), 1 had local excision, 3 had bypass, and 2 were not explored. Of the 21 patients who survived pancreaticoduodenectomy, 4 had tumor confined to the ampulla, 7 had tumor extending into the duodenum, and 10 had tumor invasion beyond the duodenum. Nine of these patients had positive lymph nodes and 12 had negative lymph nodes. The patient who had local excision was disease-free at last follow-up 104 months postoperatively. Each of the three bypassed patients died of tumor progression within 15 months. The estimated 5-year survival rate for resected patients was 60 percent and was independently related to lymph node metastases (p = 0.031) and to tumor size (p = 0.039). This experience suggests that long-term survival is possible in patients with lymph node metastases or invasive tumors extending beyond the duodenal wall and that curative pancreaticoduodenectomy can be performed with a low operative mortality; therefore, aggressive surgical resection is recommended for all patients with ampullary carcinoma.

Adenocarcinoma↗

Abdominal aortic aneurysmorrhaphy combined with biliary or gastrointestinal surgery.

Abdominal aortic aneurysms occur in 2 to 5 per cent of the population over 60 years of age. Statistically, 7 per cent of patients with aneurysms will have associated cholelithiasis. The incidence of other concomitant intra-abdominal disease is much less. Because of the catastrophic complications associated with infection of synthetic aortic grafts, most authors have advised against opening a hollow viscus during aneurysm resection. Although Staphylococcus is the predominant organism responsible for graft infections, Szilagyi and associates and Liekweg and Greenfield found gram-negative organisms in 40 per cent of infected aortic prostheses. Thomas, Bickerstaff, and Fry and their coauthors have recommended caution when considering aneurysm resection and concomitant nonvascular operations. On the other hand, there is suggestive evidence that the risk of aneurysm rupture is increased in the postoperative period, especially if the aneurysm is greater than 6 cm in diameter. Therefore, optimum management of patients with aneurysms and other intra-abdominal pathology must reduce both the risk of graft infection and the risk of postoperative rupture. To reduce morbidity and mortality rates, careful preoperative evaluation for the detection and management of coexistent disease, the proper choice of intraoperative procedures, and close postoperative monitoring with prompt surgical intervention, as indicated, are essential.

Aorta, Abdominal↗

The risk of stroke with occlusion of the internal carotid artery.

Reports of all cervicocephalic arteriograms (n = 1836) performed at one institution during a 10-year period were reviewed and the patients were classified into three groups according to the indication for arteriography. Group I included all patients with symptoms or findings compatible with occlusive disease of the carotid or vertebral artery (n = 806). Group II included patients with cerebrovascular symptoms unrelated to carotid or vertebral disease (e.g., patients with subarachnoid hemorrhage) (n = 367). Group III consisted of patients with no evidence of cerebrovascular disease (e.g., patients with primary and metastatic brain tumors) (n = 663). One hundred ten atherosclerotic occlusions of the internal carotid artery (ICA) were found in 106 patients in group I. Fifty-one percent of these patients had a history of stroke before arteriography, 24% had transient ischemic attacks (TIAs) or amaurosis fugax (AF), and 12% had nonhemispheric symptoms. Only 13% (1.7% of group I patients) were without symptoms. Ninety-one percent of the strokes and 75% of the TIAs or AF were ipsilateral to the ICA occlusion. Seventy-six percent of patients with stroke and 80% with ipsilateral TIAs or AF vs only 29% of patients without symptoms had contralateral stenosis of 60% diameter reduction or greater (p less than 0.003). No occlusions of the ICA occurred in groups II or III. Three hundred forty-six patients in groups II and III were more than 60 years of age. Assuming either Poisson or binomial distributions, the incidence of silent ICA occlusion in the population at large older than 60 years was estimated at less than 1% (p less than 0.03).

Adult↗

Hemodynamics of the hypogastric arterial circulation.

This study was designed to assess the major sources of collateral supply to the hypogastric arterial bed (HGA). Peak systolic HGA and radial arterial pressure were obtained before and after clamping a patent HGA and after additional clamping of the contralateral HGA, the contralateral external iliac artery (EIA), or the ipsilateral EIA both selectively and in combinations. These procedures were performed in 10 patients with aortoiliac (AI) aneurysms or occlusive disease. In seven patients with aneurysms, clamping the contralateral HGA decreased the HGA stump pressure index from 0.57 to 0.49 (p less than 0.05), and clamping only the ipsilateral EIA decreased the stump pressure index to 0.38 (p less than 0.001). In three patients with occlusive disease, clamping the contralateral HGA did not decrease the stump pressure index, clamping both the contralateral HGA and EIA decreased the index from 0.61 to 0.57 (p greater than 0.05), and clamping only the ipsilateral EIA decreased the pressure index to 0.40 (p less than 0.01). These data suggest that branches of the ipsilateral EIA femoral arterial system provide a more significant collateral pathway than the contralateral HGA. These results suggest that it is important to relieve occlusive disease in the ipsilateral EIA femoral arterial system if a patent HGA is ligated or bypassed during AI reconstructions. Conversely, it is especially important to preserve forward perfusion in a patent HGA in a patient with compromised ipsilateral EIA femoral runoff.

Aneurysm↗