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Biomedical subjects

B L Thomas

Publications and source records attributed to B L Thomas.

At least 37 records · Page 2Linked to original sources
PubMed1992

Differential expression of insulin-like growth factors I and II (IGF I and II), mRNA, peptide and binding protein 1 during mouse palate development: comparison with TGF beta peptide distribution.

Development of the mammalian secondary palate involves a series of epithelial mesenchymal interactions: during one of these, a mesenchymal signal specifies regionally distinct palatal epithelial differentiation. Extracellular matrix molecules and soluble growth factors may be involved in this signalling process. In this study, we have mapped the expression of the genes for insulin-like growth factors (IGF I and II), the peptides they encode, and the IGF binding protein 1 (IGF BP-1) during murine palatogenesis (embryonic days (E) 12-15). IGF-I gene expression was below detectable levels in the craniofacial region at all ages. IGF-I peptide was at the threshold of immunocytochemical detection and widely distributed in the palatal mesenchyme, decreasing in staining intensity from E12 to E14. By contrast, IGF-II mRNA was intensely localised in several tissues. IGF-II gene expression within the forming palate was developmentally regulated. In the vertical palatal shelves (E12 to E13) IGF-II gene expression was absent. On early E14, in the horizontal prefusion palate, significant expression was present in the palatal mesenchyme, but not the epithelium. Once palatal fusion had occurred, mesenchymal expression fell rapidly to undetectable levels. IGF-II mRNA was next detectable in the secondary palate on late E15 at sites of membranous bone formation. By contrast to the mRNA distribution, IGF-II peptide was localised predominantly in the palatal epithelia (particularly the nasal and medial edge epithelia) but also in the mesenchyme of the E14 prefusion palate. Significantly, the IGF binding protein had a similar distribution pattern to the IGF-II peptide. At all ages, the developing tongue myotubes labelled heavily for IGF-II mRNA, protein and binding protein. These data suggest that IGF-II may play a localised paracrine role during murine palatogenesis, perhaps in the mesenchymal signalling of epithelial differentiation. IGF-II may also serve to coordinate the development of the tongue and palate. The distribution of IGF-II peptide was very similar to that of TGF-beta, suggesting a possible interactive role of these growth factors during palate development. Finally, evidence that the IGF-II gene is imprinted (Ferguson-Smith et al. 1991) and may be the target for uniparental disomy in the human Beckwith Wiedemann syndrome (Henry et al. 1991), which is characterised by the overgrowth of tissues (especially the tongue) expressing IGF II in the embryo, indicates the necessity of reanalysing human cleft palate families for disruption (including uniparental disomy) of the genes encoding IGFs, their receptors and binding proteins.

Animals↗
PubMed1991

Incidence and clinical epidemiology of streptococcal septicemia during treatment of acute myeloid leukemia.

The incidence and outcome of streptococcal septicemia was analyzed in 76 consecutive patients with newly diagnosed and relapsed acute myeloid leukemia. They received 215 courses of remission induction or intensive consolidation treatment. There were 31 different episodes of streptococcal septicemia in 27 patients, making these microorganisms the most frequently encountered bacteria in blood cultures. This high incidence coincided with the introduction of selective intestinal decontamination. In 24 episodes (20 patients) there was a fast recovery, but 7 patients developed pulmonary symptoms resulting in death due to respiratory failure in 5 of them. The infections all occurred in the phase of maximum bone marrow suppression 1-3 weeks after the start of the chemotherapy. Streptococcal septicemia was not limited to patients treated with cytosine arabinoside but also occurred in patients treated with other regimens of intensive chemotherapy. In 28 episodes there were no focal signs of infection, but in half there were symptoms of treatment induced gastrointestinal toxicity. The streptococci probably invade through oral and gastrointestinal mucosa damaged by the chemotherapy. Selective decontamination may play a promoting role.

Adult↗
PubMed1991

Analysis of skin grafting techniques in the fetal rabbit.

The experimental model reported here was developed initially to examine the possibility of in utero coverage of congenital soft tissue defects using several types of reconstructive techniques. To pursue this, full-thickness skin grafts, pedicle flaps, and skin "islands" were fashioned on the backs of fetal rabbits; equivalent adult control wounds were also created. While all pedicle flaps and skin islands remained viable, none of the full-thickness grafts survived in the fetus. All adult control flaps, skin islands, and skin grafts were viable. Angiogenesis is crucial to full-thickness skin graft survival. These observations suggest that the death of full-thickness fetal skin grafts may be related to a failure of neovascularization in the graft bed. Further analysis using this model may help elucidate the factors involved in fetal angiogenesis. Additionally, this model may permit testing of putative angiogenic factors applied under a full-thickness skin graft; graft survival offers an easy, objective, and quantifiable means of data analysis.

Animals↗
PubMed1989

Inhibition of benzo[a]pyrene-7,8-diol formation in vitro by complex organic mixtures.

Coal-derived complex organic mixtures [COM] with boiling points greater than or equal to 370 degrees C (greater than or equal to 700 degrees F) are known to inhibit both mouse skin tumor initiation by benzo[a]pyrene [BAP], and BAP-induced bacterial mutagenesis. We have examined the effects of 5 COM, with boiling points of 149-370 degrees C (300-700 degrees F), 370-398 degrees C (700-750 degrees F), 398-426 degrees C (750-800 degrees F), 426-454 degrees C (800-850 degrees F), and greater than 454 degrees C (greater than 850 degrees F), on both the rate and the route of BAP metabolism by rat liver homogenates in vitro. When co-metabolized in 40:1 excess with BAP, all of the COM reduced the rate of BAP metabolism. The 149-370 degrees C (300-700 degrees F) COM reduced the initial rate of BAP metabolism to 34% of the rate for BAP alone, while the four higher-boiling COM reduced it to 6.3-9.3% of the rate for BAP alone. In addition, the 2 highest-boiling COM (426-454 degrees C and greater than 454 degrees C boiling points) were found to reduce the percentage of BAP metabolized to BAP-7,8-diol, in comparison to incubations using BAP alone. The 370-398 degrees C and 398-426 degrees C COM did not alter the percentage of BAP metabolized to BAP-7,8-diol, while the 149-370 degrees C COM increased it. Both the general inhibition of BAP metabolism (by all of the COM), and the specific inhibition of BAP-7,8-diol formation (by the highest-boiling COM) may play a role in the inhibition of formation of BAP-induced skin tumors by these materials.

Animals↗
PubMed1989

Analysis of transforming growth factor beta receptor binding in embryonic, fetal, and adult rabbit fibroblasts.

Adult wound repair traits including inflammation, fibroplasia, and collagen deposition are not seen at fetal wound sites. This observation raised questions about regulatory mechanisms extant in fetal healing. Transforming growth factor beta (TGF-beta) is an important regulatory polypeptide known to orchestrate fibroplasia and collagen synthesis during adult wound repair. Previous studies have suggested that the wounded rabbit fetus is capable of responding with these adult characteristics if provided with exogenous TGF-beta. In order to test whether the observed in vivo effects of TGF-beta in the rabbit fetus might be due to a direct effect on the fibroblast, TGF-beta receptor binding characteristics of early passage cultured embryonic (14 days' gestation), fetal (24 days' gestation), and adult rabbit fibroblasts were studied by flow cytometry. Experiments were carried out using fluorescein-conjugated TGF-beta (F-TGF-beta) with analysis on an EPICS V flow cytometer. F-TGF-beta was incubated with each of the three fibroblast types at 37 degrees C after which time the cells were washed twice and analyzed with a minimum of 10(5) cells for each data point. F-TGF-beta bound rapidly and reversibly to the embryonic, fetal, and adult fibroblasts with saturation being achieved at 1 nmol/L for fetal and adult cells, and 8 nmol/L in the embryonic fibroblasts. Saturating concentrations of F-TGF-beta yielded mean channel numbers (a function of relative amounts of F-TGF-beta-bound) of 172, 114, and 97 for embryonic, fetal, and adult cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Use of intraoperative ultrasound during hepatic resection in pediatric patients.

Five pediatric patients with primary liver tumors were evaluated preoperatively with ultrasound (US), computerized tomography (CT), and angiography, and tentative operative plans were formulated. Intraoperative US was subsequently used to examine these children, resulting in changes in operative strategy of all five patients despite their extensive preoperative evaluations. Intraoperative ultrasound appears to provide the most accurate assessment of both the extent of tumor and its vascular relationships. Thus, operative strategies may be precisely tailored on the basis of such information, allowing rational resection where appropriate, while futile attempts at removal of inoperable lesions may be averted.

Carcinoma, Hepatocellular↗
PubMed1989

Characterization and quantitation of wound matrix in the fetal rabbit.

Fetal response to injury has been characterized by the deposition of a matrix that is not primarily collagen. This study was designed to identify this matrix, in order to better understand the fetal mechanism of tissue repair. Silastic/polyvinyl alcohol sponge (PVA) wound implants were placed paravertebrally in 24-day gestation (31 days = term) fetal (n = 65) and adult (n = 43) rabbits and then harvested from one hour to 6 days post-wounding. Histologic analysis of the fetal wound matrix deposited in the PVA implants suggested the presence of glycosaminoglycans (GAG) rather than the collagen found in adult wound implants. To further analyze the fetal wound matrix, the GAG content was quantitated using an Alcian Blue dye-binding assay. Results showed significantly increased (p less than 0.05) GAG deposition on days 2-6 in the fetal wound compared to the adult wound. Fetal GAG levels were approximately three times those of the adult during this period. Separation of individual GAG species by cellulose acetate electrophoresis demonstrated that the GAG matrix of the fetal wound was composed predominantly of hyaluronic acid. This finding was confirmed by selective enzymatic digestion of separated GAG species using highly specific polysaccharidases. These observations of hyaluronic acid deposition in the fetal wound may be ascribed an important physiologic role by providing a more fluid and malleable matrix rather than a restrictive matrix composed of collagen. This new evidence coupled with earlier findings of the lack of an acute inflammatory response in the fetus further supports the hypothesis that the fetal response to injury is significantly different from the adult response.

Alcian Blue↗
PubMed1989

Influences of complex organic mixtures on tumor-initiating activity, DNA binding and adducts of benzo[a]pyrene.

Co-incubation of benzo[a]pyrene (BaP) and coal-derived complex organic mixtures has been shown to decrease the metabolism and mutagenic activity of BaP. Because of these influences, five mixtures were co-administered dermally to mice to initiate tumor development. Results from these studies demonstrated that BaP tumor-initiating activity was decreased substantially by four of the five mixtures. When one of the mixtures was separated into chemical class fractions, the polycyclic aromatic hydrocarbon (PAH) and nitrogen-containing polycyclic aromatic compound fractions were the most effective, and the aliphatic and hydroxy-PAH fractions were the least effective as inhibitors of BaP-induced tumor initiation. Binding of [3H]BaP to epidermal DNA under conditions identical to those used for tumor initiation was decreased by co-administration of all five mixtures. Calculations of the number of tumors produced/micrograms BaP bound to DNA demonstrated that co-administration of this carcinogen with the mixtures consistently increased the effectiveness of the bound BaP at producing tumors by approximately a factor of 2. The HPLC radioactivity profiles of enzyme-hydrolyzed, adducted DNA indicated that, in the presence of the mixtures, the predominant adducts were derived from BaP-diol epoxide (BPDE); however, the mixtures decreased the ratios of the anti-BPDE-deoxyguanosine to syn-BPDE-deoxy-guanosine adducts. These data indicate that the prevailing influences of the mixtures (i.e. decreased DNA binding and adduct shifts) were similar to those observed with other bioassays following co-administration of binary mixtures. Furthermore, the data demonstrate that both DNA binding and adduct profiles are important in determining the contribution of a known carcinogen to tumor initiation by complex organic mixtures.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1989

Preparation of microgram quantities of BaP-DNA adducts using isolated rat hepatocytes in vitro.

The analysis of carcinogen-DNA adducts generally requires the preparation (by chemical or biological means) of DNA adduct standards, in amounts sufficient for chemical characterization. We have established conditions for the in vitro biological preparation of microgram quantities of DNA adducts derived from benzo[a]pyrene (BaP), fluoranthene and 7,12-dimethylbenzanthracene, using isolated rat hepatocytes. The metabolic activation of 180 microM BaP by isolated rat hepatocytes in a calf-thymus-DNA (CT-DNA)-supplemented medium resulted in the formation of 2.9 micrograms of BaP adducted to 56.7 mg of DNA. The average level of binding in this experiment was 148 +/- 8 pmol BaP bound/1 mg DNA, which compares favorably to the 10-30 pmol BAP/1 mg DNA which is typical of mouse skin adducts in vivo. In another experiment, BaP-DNA adduct formation in calf-thymus DNA added to hepatocyte incubations was further increased to 327 +/- 27 pmol/mg DNA, by physical shearing of the DNA prior to the incubation. The HPLC profile of the BaP adducts produced using hepatocytes plus CT-DNA is virtually indistinguishable from that produced by tumor-initiating doses of BaP applied to mouse skin in vivo, and the major DNA adduct formed by the hepatocytes co-elutes with the (+)-anti-diol-epoxide adduct of deoxyguanosine. Similar experiments using fluoranthene and 7,12-dimethylbenzanthracene also resulted in substantial DNA adduct formation; however, incubations using dibenz[a,h]anthracene did not. These results indicate that isolated rat hepatocytes in vitro can be useful for the preparation of DNA adducts of a number of polycyclic aromatic hydrocarbons, in quantities sufficient for chemical characterization.

Animals↗
PubMed1988

Mass spectral characteristics of derivatized metabolites of benzo [A] pyrene.

The electron impact (EI) mass spectra of the permethyl, peracetyl and per(trifluoroacetyl) derivatives of hydroxylated benzo[a]pyrene (B[a]P) metabolites were determined and the fragmentation chemistry producing the spectra elucidated. The metabolites investigated were: 3-hydroxy-B[a]P; 7,8-dihydro-7,8-dihydroxy-B[a]P; 7,8,9,10-tetrahydro-7,8,9-trihydroxy-B[a]P; and 7,8,9,10-tetrahydro-7,8,9,10-tetrahydroxy-B[a]P. In addition, the positive and negative methane chemical ionization spectra were determined for the derivatives of the BP-tetrol. The EI fragmentation patterns of the methylated metabolites that contained partially saturated rings were complex and, in the case of the di- and trimethoxy compounds, included apparent violations of the even-electron rule. The permethylated triol and tetrol cleaved through a retro-Diels-Alder reaction. The EI spectra of the peracetates were dominated by losses of acetic acid and ketene. The per(trifluoroacetyl) species fragmented by losing elements of trifluoroacetic acid, trifluoracetate radical and trifluoroacetyl. The spectra obtained from the permethylated tetrol permitted accurate prediction of the corresponding permethylated derivatives of tetrol metabolites of chrysene and benz[a]anthracene. The ability to predict spectra may be useful in trace analysis of hydrocarbon metabolites in biological samples.

Benzo(a)pyrene↗
PubMed1988

Transforming growth factor beta (TGF-beta) induces fibrosis in a fetal wound model.

The adult cellular response to tissue injury is characterized by acute inflammation followed eventually by fibroblast proliferation and collagen synthesis. Fetal tissue responses to injury differ markedly from those of the adult; an early acute inflammatory response is absent, few fibroblasts participate, and no collagen is deposited. The object of the present study was to analyze the effects of transforming growth factor beta (TGF-beta), an important regulatory molecule in adult healing events, on the fetal tissue response following wounding. Fetal cellular and extracellular matrix responses to injury were evaluated by placing subcutaneous wound implants containing TGF-beta (0.01 to 10 ng) in fetal rabbits at 24 days gestation (term = 31 days). Histologic responses one to seven days later were compared with fetal and adult control implants without TGF-beta. The histology of the adult implant was characterized by an early acute inflammatory response: by day 7 fibroblasts and collagen were predominant. In contrast, control implants removed from fetal rabbits had no histologic evidence of acute inflammation or fibroblast penetration and no collagen was deposited. When implants containing 1.0 ng TGF-beta were removed from fetal rabbits at seven days, a grossly fibrotic reaction was observed: histology confirmed marked fibroblast penetration with collagen deposition. Fetal implants containing 0.01 ng or 10 ng TGF-beta showed few fibroblasts but had increased numbers of inflammatory cells compared with controls. These observations demonstrate that the fetal response becomes adultlike with fibroblast proliferation and collagen accumulation when TGF-beta is added, thus documenting the responsiveness of the fetal system to adult repair signals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Glucose and insulin response in diabetic subjects: acute effect of carbohydrate level and the addition of soy polysaccharide in defined-formula diets.

This single-meal pilot study compared the plasma glucose and serum insulin response to defined-formula diets with two levels of carbohydrate (CHO) (55% and 30% of the kilocalories) with and without added soy polysaccharide (10 g) in subjects with type 2 diabetes mellitus. Subjects received each of the four liquid-formula test meals in a randomly assigned order: 1) high CHO, low fiber (HC, LF), 2) high CHO, high fiber (HC, HF), 3) low CHO, low fiber (LC, LF), and 4) low CHO, high fiber (LC, HF). On the day of each test meal the formula was consumed, eight blood samples were drawn for plasma glucose and serum insulin measurements, and a 4-h urine collection was obtained for measuring glucose excretion. Our results showed that area increments under glucose and insulin curves were significantly lower with both low-CHO formulas (p less than 0.001). The addition of soy polysaccharide to the liquid formula did not result in statistically different area increments for glucose or insulin.

Adult↗
PubMed1987

Effect of L-tryptophan and phenylalanine on burning pain threshold.

The purpose of this study was to determine the effects of ingestion of L-tryptophan or phenylalanine on burning pain threshold using a double blind, pretest-posttest control group design. Sixty healthy, female student volunteers were assigned randomly to L-tryptophan, phenylalanine, or placebo groups, (Groups 1-3, respectively). The pretest radiant heat tolerance was determined for all subjects. Burning pain tolerance was defined as the amount of time in seconds from the initial exposure of the left fifth distal phalanx to a 250-W infrared lamp until the subject's detection of an "intense burning sensation." The subjects in Groups 1 and 2 ingested four 500-mg tablets of phenylalanine or L-tryptophan a day for 14 days. The placebo group ingested four placebo tablets a day for 14 days. Immediately after the 14th day, the radiant heat pain tolerance of all subjects was remeasured. The results of a one-way analysis of covariance showed no significant difference in the posttest pain tolerance values of the three groups.

Adult↗