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Biomedical subjects

S D Wilson

Publications and source records attributed to S D Wilson.

At least 37 records · Page 2Linked to original sources

Centration mechanism of soft contact lenses.

A theoretical model is developed in which the force that restores a soft hydrogel lens to its centered position is ascribed to flexure of the lens. It is shown that flexure makes the dominant contribution to the strain energy in the displaced position. The restoring force is calculated explicitly. The return speed is estimated explicitly, assuming that the dominant resisting force is the viscous drag offered by the postlens tear film. Satisfactory agreement with observations is found.

Contact Lenses, Hydrophilic↗

Nucleotide sequence of the gene encoding the viral polymerase of avian pneumovirus.

We report here the nucleotide sequence of the L gene of avian pneumovirus (APV). This is the second pneumovirus L gene and the second avian paramyxovirus L gene, following that of Newcastle disease virus, to be sequenced. The APV L gene is 6099 nucleotides long and encodes a single large ORF of 2004 amino acids. This makes the APV L protein the smallest to be described for any nonsegmented, negative-strand RNA virus. The protein contains six linear non-contiguous domains, a putative ATP-binding site and four polymerase motifs previously described for the L proteins of negative-strand RNA viruses. Phylogenetic analysis of domain III of 14 different L proteins suggests the pneumoviruses to be as distant in evolutionary terms from the other members of the Paramyxoviridae as are the Filoviridae.

Amino Acid Sequence↗

Penetration of ciprofloxacin and fleroxacin into biliary tract.

Forty patients with chronic cholecystitis or cholelithiasis were prospectively randomized for therapy with either ciprofloxacin or fleroxacin to study the penetration of these two agents into gallbladder tissue, plasma, and bile. Patients received a 3-day course of ciprofloxacin (500 mg twice a day) or fleroxacin (400 mg once daily) and were subdivided into four groups reflecting intraoperative sample collection at 4, 7, 14, and 25 to 26 h following the last quinolone dose. Mean concentrations in plasma for ciprofloxacin and fleroxacin at 4 and 25 to 26 h postdose were 2.5 and 10 micrograms/ml and 0.3 and 1.8 micrograms/ml, respectively. The concentrations of ciprofloxacin and fleroxacin in bile and gallbladder wall tissue at 25 to 26 h postdose were 4.5 and 8.6 micrograms/ml and 1.2 and 4.4 micrograms/ml, respectively. Both agents demonstrate rapid tissue penetration with persistence at levels appropriate for treatment of biliary pathogens.

Adolescent↗

Increased plasminogen activator and type IV collagenase activity in invasive follicular thyroid carcinoma cells.

BACKGROUND: An essential difference between benign and malignant follicular thyroid tumors is the ability to invade and metastasize. Thyrotropin (TSH) stimulates invasion of cultured human follicular thyroid cancer cells (FTC-133) via a protein kinase C (PKC) dependent mechanism. Tumor invasion depends on degradation of extracellular matrix by proteases. METHODS: We analyzed protease activity in FTC-133 and its more invasive clone, FTC-238. Cells were treated with TSH or 12-0-tetradecanoyl-phorbol-13-acetate (TPA), a PKC agonist, for 24 hours. Conditioned medium and cellular extract were subjected to substrate gel zymography with either casein-plasminogen or gelatin (collagen). Western blot and immunohistochemistry confirmed protease identity. RESULTS: We found increased 50 kd urokinase-like plasminogen activator (uPA) and 62 kd gelatinase activity by FTC-238 cells compared with the less invasive FTC-133 cells. There was no effect of TSH on uPA or collagenase activity at concentrations of 0.01 to 10 mU/ml. In both FTC-133 and FTC-238, TPA incubations of 0.1 to 100 ng/ml caused a dose-dependent increase in uPA and a 94 kd type IV collagenase. CONCLUSIONS: These findings show that TSH-stimulated invasion may be due to PKC-induced activation of uPA and 94 kd type IV collagenase. uPA and basement membrane type IV collagenase warrant investigation as markers for follicular thyroid cancer.

Adenoma↗

Post-lens tear film thinning in rigid gas permeable lenses.

An attempt is made to gain a greater understanding of lens binding during overnight wear. To do this, a mathematical model is used to investigate the motion of a rigid gas permeable (RGP) lens normal to the eye surface, when the eye is closed. Graphs of the displacement of the lens as a function of time are computed for different lens designs. The rate of apical tear film thinning is found to depend upon the central fitting relation, with lenses that are fitted flatter giving the highest rate of thinning. The model also suggests the relevance of other factors such as eyelid muscle tension and tear-layer composition during sleep to the clinical phenomenon of lens binding.

Blinking↗

Routine or selective intraoperative cholangiography in laparoscopic cholecystectomy.

The routine versus selective use of intraoperative cholangiography has been the subject of debate for some time. Most authors currently advocate routine intraoperative cholangiography with laparoscopic cholecystectomy. The authors report their experience with the selective and routine utilization of intraoperative cholangiography at two institutions. At institution A, 155 laparoscopic cholecystectomies were attempted, and 21 cholangiograms were performed (based on preoperative criteria of ultrasound, liver function tests, and history of jaundice, or intraoperative anatomical uncertainty). At institution B, 164 laparoscopic cholecystectomies were attempted and 127 cholangiograms were performed (a routine intraoperative cholangiography policy). At institution A, there were no common bile duct injuries but there was one retained stone. At institution B, there was one common bile duct injury and no retained stones. The patient with the retained stone from institution A had a preoperative indication (total bilirubin = 4.4 mg/dl) for a cholangiogram, but it was not performed due to technical difficulties. This patient later required endoscopic sphincterotomy with stone extraction. One patient at institution B had a choledochotomy which was detected by intraoperative cholangiography (IOC). This was managed with a T-tube. The selective use of cholangiograms in laparoscopic cholecystectomy will not yield a higher incidence of common bile duct injuries or retained stones compared to routine use. Further, a cholangiogram may not necessarily prevent choledochotomy but can prevent extension of common bile duct injury. Thus, it should always be performed when there is anatomic uncertainty.

Cholangiopancreatography, Endoscopic Retrograde↗

Zollinger-Ellison syndrome in children: a 25-year follow-up.

The influence of gastric resection on the Zollinger-Ellison syndrome (ZES) in eight children was first reported to the Central Surgical Association 26 years ago. That report showed that the three children who had less than total gastrectomy were all dead with complications of gastric acid hypersecretion, although the five children who had total gastrectomy were living and well. During the past quarter of the century, the development of effective gastric acid inhibitors has prompted a greater emphasis on medical management in the ZES. The role of the surgeon and total gastrectomy remains controversial. Follow-up of the five young patients who had total gastrectomy shows that only one patient was dead with tumor 14 years after total gastrectomy and that the remaining four patients were alive 30, 29, 28, and 27 years, respectively, after total gastrectomy. Growth and activity have been near normal. All patients have had proven metastatic islet-cell carcinoma documented at some time in the course of the disease (lymph nodes in three patients and liver metastasis in two patients). Only one of the four living patients with total gastrectomy had a normal serum gastrin level and no apparent tumor. Gastrinoma tumor growth appears to be less aggressive in children than in adults. Complete excision of gastrinomas is possible in some patients with ZES. When hypergastrinemia persists, total gastrectomy may be preferable to lifelong medical management with gastric acid inhibitors in children and young adults with ZES.

Adolescent↗

Sequence and chromosomal location of the I-309 gene. Relationship to genes encoding a family of inflammatory cytokines.

We previously reported the isolation and characterization of a cDNA clone, I-309, that encodes a small secreted protein produced by activated human T lymphocytes. This protein is structurally related to a large number of recently identified proteins that are secreted upon cellular activation. In this report we describe the isolation and characterization of the gene encoding I-309. The genomic organization is essentially identical to that found in the genes encoding the structurally similar proteins TCA-3, hJE/MCP-1, and mJE, strengthening the hypothesis that these genes are evolutionarily related. The region of the I-309 gene 5' of the mRNA cap site exhibits extensive nucleotide sequence homology with the same region of the murine gene TCA-3, providing additional evidence that I-309 and TCA-3 are likely to be homologs. Finally, panels of rodent-human somatic cell hybrids were used to map the I-309 gene to human chromosome 17. In conjunction with recent mapping data from other laboratories, this result suggests the presence of a cluster of related genes on this chromosome.

Amino Acid Sequence↗

Expression and characterization of TCA3: a murine inflammatory protein.

TCA3 is a cDNA originally isolated from activated T cells. Transcription of this gene has been shown to correlate with Ag-induced cellular activation of both T cells and mast cells. Based on the predicted amino acid sequence encoded by the cDNA, we previously proposed that TCA3 represents a cytokine. In this report we have used rDNA technology to express TCA3 in two mammalian cell lines. In both cases, TCA3 was expressed as a secreted molecule with an apparent molecular mass of 16 kDa. Digestion of the (rTCA3) with the enzyme N-glycanase revealed that approximately 8 kDa is caused by N-linked glycosylation. Intradermal injection of rTCA3 into mouse footpads resulted in a rapid swelling response. The sites of injection were characterized histologically by a local accumulation of neutrophils. These findings are discussed with particular attention to a family of related proteins, some of whose members also have inflammatory properties.

Animals↗

Clustering of cytokine genes on mouse chromosome 11.

The presence of positionally conserved amino acid residues suggests that the mouse proteins TCA3, P500, MIP1-alpha, MIP1-beta, and JE are members of a single gene family. These proteins are activation specific and can be expressed by both myeloid and lymphoid cells. MIP1-alpha/MIP1-beta and MCAF (the putative human homologue of JE) act as chemotactic and activating agents for neutrophils and macrophages, respectively. The functions of TCA3 and P500 are unknown. We have used interspecies somatic cell hybrids and recombinant inbred mouse strains to show that the genes encoding TCA3, MIP1-alpha, MIP1-beta, and JE (provisionally termed Tca3, Mip-1a, Mip-1b, and Sigje, respectively) map as a cluster on the distal portion of mouse chromosome 11 near the Hox-2 gene complex. DNA sequence analysis indicates that the P500 and TCA3 proteins are encoded by alternative splicing products of one genomic gene. Additionally, the genes encoding TCA3 and JE are found to be strikingly similar with respect to the positions of intron-exon boundaries. Together, these data support the model that the cytokines TCA3, P500, MIP1-alpha, MIP1-beta, and JE are encoded by a single cluster of related genes. The gene encoding IL-5 (Il-5), which acts as a T cell-replacing factor, a B cell growth factor, and an eosinophil differentiation factor, is also mapped to mouse chromosome 11.Il-5 maps approximately 25 cM proximal to the Tca-3 gene and appears tightly linked to a previously described gene cluster that includes Il-3, Il-4, and Csfgm. We discuss the potential relevance of the two cytokine gene clusters described here with particular attention to specific human hematologic malignancies associated with chromosomal aberrations at corresponding locations on human chromosomes 5 and 17.

Amino Acid Sequence↗

Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome.

A large previously reported family with hyperparathyroidism has been reinvestigated recently because of the occurrence of multiple ossifying jaw fibromas in two affected members of the third generation similar to the jaw tumors of four of five affected members of the first generation. These maxillary and mandibular tumors can be differentiated from the "brown tumors" of hyperparathyroidism because they can appear and enlarge even though the hypercalcemia is surgically corrected. These tumors are histologically distinct fibroosseous lesions without the giant cells seen in "brown tumors." The parathyroid enlargement was mostly uniglandular, with multiple tumors found occasionally. Studies in DNA linkage were performed within this large family and a similar family in Houston to determine if the gene for this syndrome, termed HRPT2, is linked to DNA markers on chromosome 11, to which the gene for multiple endocrine neoplasia (MEN) type 1 has been linked. (This linkage is supported by our findings in one family with MEN 1 reported here.) Linkage studies were also performed with markers on chromosome 10, to which the genes for MEN 2A and MEN 2B have been linked. Evidence against close linkage with chromosome 10 and chromosome 11 markers suggests that this clinically distinct syndrome is also genetically distinct.

Female↗

Interleukin 3-dependent and -independent mast cells stimulated with IgE and antigen express multiple cytokines.

In response to IgE and specific multivalent antigen, mast cell lines (both growth factor-dependent and -independent) induce the transcription and/or secretion of a number of cytokines having a wide spectrum of activities. We have identified IL-1, IL-3, IL-5, IL-6, IFN-gamma, GM-CSF, JE, MIP1 alpha, MIP1 beta, and TCA3 RNA in at least two of four mast cell clones. The production of these products (except JE) is activation-associated and can be induced by IgE plus antigen. In selected instances cytokine expression can also be induced by activation with Con A or phorbol ester plus ionophore, albeit to levels less than those observed with IgE plus antigen. In addition, long-term mast cell clones and primary cultures of bone marrow-derived mast cells specifically release IL-1, IL-4, and/or IL-6 bioactivity after activation. These findings suggest that in addition to their inflammatory effector function mast cells may serve as a source of growth and regulatory factors. The relationship of mast cells to cells of the T lymphocyte lineage is discussed.

Animals↗

Cholelithiasis follows total gastrectomy in Zollinger-Ellison syndrome.

The frequent occurrence of cholelithiasis noted in the follow-up of patients who underwent total gastrectomy because of Zollinger-Ellison syndrome prompted us to study this phenomenon. Cholelithiasis is known to be more common after truncal vagotomy, with or without concomitant subtotal gastric resection, and the prevalence of gallstones in these patients is reported to be 16% to 38%. To date, however, no long-term study has investigated the prevalence of gallstones after total gastrectomy in patients with the Zollinger-Ellison syndrome. Since 1961, 26 patients with the Zollinger-Ellison syndrome have undergone total gastrectomy and were enrolled in a Medical College of Wisconsin Clinical Research Center protocol that allowed follow-up to assess the development of cholelithiasis. Eight patients had cholecystectomy at the time of total gastrectomy (seven patients had stones), leaving 18 patients with a normal gallbladder and no gallstones at the time of total gastrectomy. Four patients died early, two of surgical complications, one of tumor progression, and one of alcohol-related trauma. During follow-up, cholelithiasis has developed in 10 of 14 patients (71%) at risk; the mean time to gallstones was 6.3 years (range, 1.2 to 12.9 years). The predictable occurrence of cholelithiasis after total gastrectomy in patients with the Zollinger-Ellison syndrome suggests that cholecystectomy should be performed at the time of total gastrectomy.

Adult↗

Prospective comparison of radionuclide, computed tomographic, sonographic, and magnetic resonance localization of parathyroid tumors.

The appropriate choice of imaging techniques to localize parathyroid tumors preoperatively remains controversial. We report the first prospective, blinded study to compare the efficacy of four imaging modalities in 100 patients with primary hyperparathyroidism (pHPT). Patients were examined by computer-assisted thallium 201/technetium 99m subtraction scintigraphy (TTS), computed tomography (CT), ultrasonography (US), and magnetic resonance (MR). Each study was performed and interpreted independently. Subsequent neck exploration and "curative" parathyroidectomy allowed correlation of surgical findings with imaging reports to score their accuracy. Overall sensitivities of the four imaging modalities were TTS, 73%, CT, 68%, US, 55%; and MR, 57%; with respective specificities of 94%, 92%, 95%, and 87%. Sensitivities for lesions located below the thyroid gland (thymic tongue and mediastinum) were TTS, 90%; CT, 46%; US, 44%; and MR, 50%; with respective specificities of 100%, 99%, 100%, and 94%. There was a significant increase in overall sensitivity when TTS and CT (90%, p less than 0.01) or TTS and US (85%, p less than 0.05) were used together; however, the combination of any three or even four imaging modalities did not increase sensitivity further. For small parathyroid tumors (less than or equal to 250 mg), no imaging technique had a sensitivity of more than 50%. None of the imaging studies accurately localized small hyperplastic parathyroid glands found in patients with multiple gland disease. Preoperative parathyroid imaging may not be indicated in pHPT patients undergoing first-time neck exploration because surgeons experienced in parathyroid surgery have a 93% to 96% cure rate.

Adult↗

The expression and regulation of a potential lymphokine gene (TCA3) in CD4 and CD8 T cell clones.

The TCA3 gene was originally isolated from a cDNA library derived from a TH1 (inflammatory) T cell clone. Expression of TCA3 RNA was limited to cells in the activated state. Based on its expression profile and the existence of a hydrophobic leader sequence with a predicted cleavage site, we proposed that TCA3 encodes a new lymphokine. In the present study, we examine the subset distribution, kinetics, and regulation of TCA3 RNA expression. We show that TCA3 is expressed in response to selected T cell-activating stimuli. TCA3 is transcribed to peak steady state levels by 4 h after stimulation in TH1, TH2 (helper), and CTL clones. Two intracellular signals, supplied in vitro by phorbol ester and one of several agents capable of increasing intracellular free calcium concentrations, are required for the initiation of TCA3 transcription. In addition, TCA3 transcription is blocked by anti-L3T4 mAb, suggesting that prior signaling through L3T4 can inhibit expression of TCA3 and other lymphokines. In contrast to IL-2, IL-4, and IFN-gamma TCA3 is uniformly expressed at high levels among all individual T cell clones examined, including four TH1, three TH2, and three CTL clones. Furthermore, activation-specific TCA3 expression can be dissociated from T cell proliferation.

Animals↗

DNA content in radiation-associated thyroid cancer.

DNA content has been reported to be of prognostic significance in differentiated thyroid carcinoma. Since malignant tumors with irradiation as an initiator often contain DNA aberrations, the DNA content of well-differentiated thyroid carcinoma in patients with a prior history of low-dose head and neck irradiation was determined and compared with similar nonradiation-associated lesions. The DNA content of thyroid cancers from 53 patients was determined with use of flow cytometry. Sixteen radiation-associated thyroid carcinomas (11 papillary, 3 follicular, and 2 medullary) all were diploid. In a group of 37 nonradiation-associated tumors, 10 were aneuploid (10 of 29 papillary carcinomas and 0 of 2 follicular or 6 medullary carcinomas). This difference in DNA content is significant (p less than 0.02, Fisher's exact test). These findings were unexpected and suggest that if the initiating irradiation causes a DNA aberration, this aberration is not reflected in DNA content as measured by means of flow cytometry.

Adenocarcinoma↗