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Biomedical subjects

T M Williams

Publications and source records attributed to T M Williams.

At least 127 records · Page 7Linked to original sources

Interleukin-1 costimulatory activity on the interleukin-2 promoter via AP-1.

Interleukin-1 (IL-1) is a major regulator of inflammation and immunity. IL-1 induces T lymphocyte growth by acting as a second signal (together with antigen) in enhancing the production of interleukin-2 (IL-2). An IL-1-responsive element in the promoter region of the human IL-2 gene was similar to the binding site for the transcription factor AP-1. IL-1 enhanced expression of c-jun messenger RNA, whereas the antigenic signal enhanced messenger RNA expression of c-fos. Thus, the two components of the AP-1 factor are independently regulated and the AP-1 factor may serve as a nuclear mediator for the many actions of IL-1 on cells.

Animals↗

Swimming by sea otters: adaptations for low energetic cost locomotion.

The energetics and hydrodynamics of surface and submerged swimming were compared in the sea otter (Enhydra lutris). 1. Sea otters used two distinct speed ranges that varied with swimming mode. Sustained surface swimming was limited to speeds less than 0.80 m/s, while sustained submerged swimming occurred over the range of 0.60 to 1.39 m/s. 2. Rates of oxygen consumption (VO2) at the transition speed (0.80 m/s) were 41% lower for submerged swimming by sea otters in comparison to surface swimming. 3. Total cost of transport for surface swimming sea otters, 12.56 joules/kg.m, was more than 12 times the predicted value for a similarly-sized salmonid fish. Transport costs for submerged swimming at the same speed was only 7.33 times the predicted value. 4. The allometric relationship for minimum cost of transport in surface swimming birds and mammals was y = 23.87 chi -0.15 where y = cost of transport in joules/kg.m and x = body mass in kg. This regression loosely parallels the relationship for salmonid fish. 5. Correlations between aquatic behavior, morphological specialization, and swimming energetics indicate that the development of swimming in mustelids involved transitions from fore-paw to hind-paw propulsion, and from surface to submerged swimming.

Animals↗

Advantages of firefly luciferase as a reporter gene: application to the interleukin-2 gene promoter.

The chloramphenicol acetyltransferase (CAT) gene is widely used in recombinant constructs employed to study promoter and enhancer control of gene expression. However, CAT-based assays require a laborious, multi-step procedure for quantitation of promoter activity. We have applied the recently described firefly luciferase (LUC) reporter gene to the study of the interleukin-2 (IL2) promoter and have further defined the properties of this reporter gene system. We find that IL2-LUC constructs have multiple advantages over IL2-CAT constructs. The LUC assay is highly sensitive and requires 1/10 the cells used in the CAT system. A final quantitative measure of promoter activity can be obtained within 25 h following transfection with IL2-LUC, compared to 108-160 h with IL2-CAT. Light emission significantly (fourfold) above background is detectable 3 h after induction in a direct assay of extracts from transfected cells. We have described the variability of the assay, the minimum number of transfected cells required to detect light, the stability of luciferase in cell extracts, the effect of Triton X-100 on the assay, and a rapid cell lysis procedure. The luciferase system is a simple, rapid, and sensitive method for the study of promoter activity in transfected cells, particularly for weakly expressed genes such as IL2 which give low activity in the CAT assay.

Animals↗

Organ blood flow and cardiovascular effects of high-frequency oscillation versus conventional ventilation in dogs with right heart failure.

Mongrel dogs underwent a large (apex to pulmonary valve) right ventriculotomy to produce right ventricular dysfunction. Right ventriculotomy decreased cardiac output from 2.47 +/- 0.43 to 1.34 +/- 0.16 L/min (p less than .01), increased CVP from 3.7 +/- 1.5 to 8.3 +/- 2.4 mm Hg (p less than .01), and decreased mean systemic arterial pressure (MAP) from 143 +/- 16 to 121 +/- 21 mm Hg (p less than .01). There was no effect on mean pulmonary artery pressure (MPAP) or pulmonary artery occlusion pressure. After stabilization a randomized crossover controlled comparison of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) was performed. FIO2, pH, PCO2, core temperature, and preload were held constant. Mean airway pressure (Paw) was 4.8 +/- 0.7 cm H2O on CMV vs. 3.5 +/- 1.0 cm H2O on HFO (p less than .05). There was no difference in PaO2. We found no statistically significant differences between the two modes of ventilation with respect to cardiac output, MAP, MPAP, systemic vascular resistance, and pulmonary vascular resistance. Blood flows to cerebral cortex, renal cortex, adrenal, hepatic artery, left ventricular myocardium, and skeletal muscle were not different when comparing CMV to HFO. Despite the ability to attain equivalent oxygenation and ventilation at lower Paw, HFO offers no hemodynamic advantage over CMV in the presence of right ventricular dysfunction.

Animals↗

Liver transplantation.

A multidisciplinary approach is necessary in addressing the needs of a patient with end-stage liver disease. The development of the liver transplant program at MHI was a natural extension of the transplant and critical care programs already in place. The case report described exemplifies that valuable input from ancillary support groups is necessary for a successful liver transplant program. Experience gained in the area of liver transplantation not only benefits liver transplant patients but also extends to other areas of clinical medicine. One year ago, an Indiana resident had to travel out of state to receive this specialized form of care. Today this is no longer the case.

Humans↗

Autoantigenic germ cells exist outside the blood testis barrier.

Preleptotene spermatocytes and spermatogonia are germ cells located outside the blood-testis barrier provided by the Sertoli cells. These cells have been found to express autoantigens accessible to circulating antibodies. Mice immunized with syngeneic testis with or without bacterial adjuvant had detectable IgG on cells at the periphery of seminiferous tubules. Sera from orchiectomized but not from testes-intact mice immunized with testis and adjuvants readily transferred similar IgG deposits to testes of normal recipients. When testis-specific antisera from orchiectomized mice and testis-intact mice were compared for their reactivity on prepuberal testicular cells, serum from orchiectomized donors had significantly higher reactivity. Ig was eluted from IgG-positive testes with acid buffer and was shown to be highly enriched in antibody to prepuberal testicular cells, confirming the Ag-specific nature of the IgG deposits. The testis IgG deposits reacted with antisera to IgG1 and IgG3 but not IgG2a or IgG2b. This finding can explain lack of association of C3 in the deposits. Only 30 to 40% of seminiferous tubules had IgG deposits and they coincided with stages 7 to 12 of the spermatogenic cycle. Thus, the expression of the autoantigens is stage specific. The in situ formation of immune complexes by circulating autoantibodies demonstrates conclusively that testis autoantigens are not completely sequestered, and the blood-testis barrier as an immunologic barrier is incomplete.

Aging↗

Two regions within the human IL-2 gene promoter are important for inducible IL-2 expression.

We have examined regulatory domains of the human IL-2 gene promoter by transfection and transient expression of rDNA constructs in which the chloramphenicol acetyl transferase gene shows T cell-specific inducible expression and cyclosporin A-mediated inhibition when placed downstream of 587 bp of the human IL-2 5'-flanking region. A series of 5'-deletion constructs transfected into the Jurkat T lymphoid line demonstrates that a region encompassing 370 bp 5' of the transcription start site is sufficient for inducible chloramphenicol acetyl-transferase expression. Further dissection of this region with internal deletion (linker-scanner) mutants revealed that portions of at least two discrete regions from -42 to -169 and -289 to -361 bp relative to the transcription start site are critical for inducible expression of the IL-2 gene. T cell-specific expression of wild-type and mutant IL-2 promoter constructs could be increased severalfold by the insertion of an upstream SV40 enhancer. With use of a battery of IL-2 promoter constructs, we could not identify subregions within IL-2 5'-flanking sequences which are crucial for cyclosporin A inhibition of the IL-2 gene or deletion of which resulted in loss of T cell-specific expression, suggesting that such functions may be mediated at pre-transcriptional levels.

Acetyltransferases↗

Ultrastructure of Thiothrix spp. and "Type 021N" Bacteria.

The ultrastructural features of two groups of filamentous sulfur bacteria, Thiothrix spp. and an unnamed organism designated "type 021N," were examined by transmission electron microscopy. Negative staining of whole cells and filaments with uranyl acetate revealed the presence of tufts of fimbriae located at the ends of individual gonidia of Thiothrix sp. strain A1 and "type 021N" strain N7. Holdfast material present at the center of mature rosettes was observed in thin sections stained with ruthenium red. A clearly defined sheath enveloped the trichomes of two of three Thiothrix strains but was absent from "type 021N" filaments. The outer cell wall appeared more complex in "type 021N" strains than in Thiothrix isolates. Bulbs or clusters of irregularly shaped cells, often present in filaments of "type 021N" bacteria, appeared to result from crosswalls which formed at angles oblique to the filament axis. The multicellular nature of these sulfur bacteria was apparent in that only the cytoplasmic membrane and peptidoglycan layer of the cell wall were involved in the septation process. Sulfur inclusions which developed in the presence of sodium thiosulfate were enclosed by a single-layered envelope and located within invaginations of the cytoplasmic membrane.

Journal Article↗

Genetic risk for recombinant 8 syndrome and the transmission rate of balanced inversion 8 in the Hispanic population of the southwestern United States.

A rec(8) dup(q) syndrome, secondary to a pericentric inversion--inv(8)(p23q22)--has been identified in 26 probands from Hispanic kindreds in the southwestern United States. The clinical phenotype of the Hispanic rec(8) syndrome includes a dysmorphic facies, cardiovascular and urinary-tract malformations, and mental retardation. Segregation analysis utilizing pedigree and cytogenetic data from 31 kindreds including five additional kindreds from additional sources has provided computation of genetic risks for counseling. An inv(8) carrier parent has a 6.2% risk of having a rec(8) child. The transmission rate of the inv(8) was significantly higher for inv(8) carrier mothers (59%) than for carrier fathers (42%). The combined transmission rate for both sexes was 53%. Risk for spontaneous abortion or stillbirth (11.3%) was not higher than the general population frequency of 13%-15%. It is significant that all kindreds identified to date are of Hispanic background with ancestors traced to the southern Colorado/northern New Mexico region. By means of extended pedigree information, three independently ascertained kindreds have been linked through common ancestry 4 generations in ascendance. The Hispanic background, geographic localization, and common ancestry in three kindreds suggest a single founder of the Hispanic inv(8) in the Southwest.

Chromosome Inversion↗

Nontuberculous mycobacterial infection in AIDS: clinical, pathologic, and radiographic features.

The medical records, radiographs, and pathologic specimens of ten patients with the diagnoses of nontuberculous mycobacterial infection and acquired immunodeficiency syndrome (AIDS) were examined. The radiographic findings of alveolar or nodular infiltrates and adenopathy were relatively nonspecific but in most cases led to bronchoscopic study or open-lung biopsy, which established the diagnosis. Bronchoscopic washings or sputum cultures, which frequently provided the first confirmation of infection, were always followed by positive blood or tissue cultures. In contrast to nontuberculous infection in immunocompetent hosts, disseminated infection was common, with evidence of extrapulmonary involvement in nine patients. On the basis of these findings, we recommend that any AIDS patient with sputum or bronchoscopic washings demonstrating nontuberculous mycobacterial organisms be tentatively classified as having disseminated infection while being evaluated with blood, bone-marrow, stool, and urine cultures, even if the chest radiograph shows no disease.

Acquired Immunodeficiency Syndrome↗

Filamentous sulfur bacteria of activated sludge: characterization of Thiothrix, Beggiatoa, and Eikelboom type 021N strains.

Seventeen strains of filamentous sulfur bacteria were isolated in axenic culture from activated sludge mixed liquor samples and sulfide-gradient enrichment cultures. Isolation procedures involved plating a concentrated inoculum of washed filaments onto media containing sulfide or thiosulfate. The isolates were identified as Thiothrix spp., Beggiatoa spp., and an organism of uncertain taxonomic status, designated type 021N. All bacteria were gram negative, reduced nitrate, and formed long, multicellular trichomes with internal reserves of sulfur, volutin, and sudanophilic material. Thiothrix spp. formed rosettes and gonidia, and four of six strains were ensheathed. Type 021N organisms utilized glucose, lacked a sheath, and differed from Thiothrix spp. in several aspects of cellular and cultural morphology. Beggiatoa spp. lacked catalase and oxidase, and filaments were motile. Biochemical and physiological characterization of the isolates revealed important distinguishing features between the three groups of bacteria. Strain differences were most evident among the Thiothrix cultures. A comparison of the filamentous sulfur bacteria with freshwater strains of Leucothrix was made also.

Bacteroidetes↗

Clinicopathologic and dysmorphic findings in recombinant chromosome 8 syndrome.

Clinical records, autopsy reports, and microscopic slides from 11 infants with the recombinant 8 syndrome, an inherited abnormality of chromosome 8 affecting Hispanics from New Mexico and Colorado, were evaluated. A prevalence of cardiac and genitourinary anomalies was found, while few central nervous system abnormalities were observed. Dysmorphic features associated with recombinant 8 syndrome are presented, with descriptions of the inheritance pattern and recurrence risk. Because recombinant 8 syndrome is a chromosomal disorder that will appear more and more frequently as kindreds enlarge, pathologists must be alert to its diagnostic characteristics and genetic implications.

Abnormalities, Multiple↗

Exposure of embalmers to formaldehyde and other chemicals.

Seven funeral homes were surveyed in 1980 to determine the magnitude of embalmers' exposure to formaldehyde, other chemical vapors, and total and respirable particulates. Air was monitored for formaldehyde by personal and area samples, and assayed using the chromotropic acid method. Personal sampling revealed time-weighted average formaldehyde concentrations which ranged from 0.1 to 0.4 ppm (mean 0.3 ppm) and 0.5 to 1.2 ppm (mean 0.9 ppm) during the embalming of intact and autopsied bodies, respectively. Concentrations of other airborne chemicals and of particulates were negligible. In preparing autopsied bodies, embalming technique and condition of the body itself appeared to be major determinants of formaldehyde exposure.

Air Pollutants, Occupational↗

Radiosensitization by derivatives of isoindole-4,7-dione.

New derivatives of isoindole -4,7-dione have been synthesized and their radiation sensitization and chemical behavior have been studied. One-electron reduction potentials have been determined by pulse radiolysis and found to be in the range of -0.45 to -0.36 V vs NHE . Radiosensitization effects were tested in vivo using soft tissue sarcoma transplanted in mice. All the isoindole -4,7-diones tested were found to exert considerable radiosensitization, approaching that of misonidazole tested under comparable conditions. The derivatives which contain a carbethoxy group on the pyrrolic ring were found to have more positive reduction potentials and to act as more efficient sensitizers. Further development of this class of radiosensitizers is underway.

Animals↗

Locomotion in the North American mink, a semi-aquatic mammal. I. Swimming energetics and body drag.

Oxygen consumption (VO2) during surface swimming and total body drag were investigated in the North American mink, Mustela vision Schreber. Over the range of 0.13-0.70 ms-1, VO2 increased curvilinearly with speed for minks swimming against a current in a water flume. Similarly, body drag of a mink carcass increased non-linearly with speed and was described by the equation, Drag = 1.24 velocity. A streamlined body shape, characteristic of many mustelids, aided in reducing drag at high speeds. Net swimming efficiencies were comparatively low (less than 2.8%) and were attributed to hig levels of drag when on the water surface and the absence of appendage specialization for aquatic locomotion. This lack of specialization probably contributes to high energetic costs but enables the mink to forage in both the aquatic and terrestrial environments.

Animals↗