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Biomedical subjects

K D Taylor

Publications and source records attributed to K D Taylor.

At least 19 recordsLinked to original sources

ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn's disease.

BACKGROUND & AIMS: In the clinical trial, a lower response to infliximab was observed in some patients after multiple infusions, suggesting that clinical subgroups of Crohn's disease (CD) exist based on response to anti-tumor necrosis factor (anti-TNF). The aim of this study was to characterize these subgroups further by antineutrophil cytoplasmic antibody (ANCA) pattern and TNF genotype. METHODS: Crohn's Disease Activity Index (CDAI) data from the North American patients in the clinical trial (n = 59) were evaluated as the response parameter. Speckled ANCA (sANCA) subjects were ANCA positive by ELISA with a speckling over the entire neutrophil on indirect immunofluorescence. Genotypes were determined for polymorphisms in the TNF/lymphotoxin alpha (LTA) region. RESULTS: Response to infliximab as median change in CDAI was placebo (least response) < perinuclear ANCA (pANCA) < not pANCA or sANCA < sANCA (greatest response) (P(overall) = 0.003; 4 weeks). The response of subjects with sANCA was significantly different from that of placebo at all time points; that of pANCA subjects was not. Homozygotes for the LTA NcoI-TNFc-aa13L-aa26 haplotype 1-1-1-1 did not respond (P(overall) = 0.007). CONCLUSIONS: These observations suggest that sANCA may identify a CD subgroup with a better response to infliximab and that pANCA and homozygosity for the LTA 1-1-1-1 haplotype may identify subgroups with a poorer response.

Antibodies, Antineutrophil Cytoplasmic↗

Dietary zinc intake of a group of long-stay mentally handicapped women: some bioavailability considerations.

Dietary factors affecting zinc bioavailability were evaluated according to their relative distribution in the individual daily meals making up the basic diet of 17 institutionalized, mentally handicapped adult women. Mean intake values of zinc, phytate, nonstarch polysaccharides (NSP), calcium, protein, and energy were calculated from a dietary survey of 7 consecutive days, which also served to obtain values for the two zinc bioavailability predictor formulas, phytate/Zn millimolar ratio and [Ca][phytate]/[Zn][energy] ratio. Mean daily zinc intake was 8.5 +/- 1.8 mg, with noon and evening meals accounting for the highest contribution to this value (45% and 35%, respectively), whereas breakfast meals' contribution was 16%. The mean protein intake was 55 +/- 13 g, with noon and evening meals being the major contributors to total daily intake (42% and 38%, respectively). Breakfast meals accounted for 77% of daily phytate intake, giving a respective phytate/Zn millimolar ratio of 20.4 +/- 7.6 and a [Ca][phytate]/[Zn][energy] ratio of 336 +/- 127 mmol/Mcal. Values for both ratios based on noon and evening meals were negligible in comparison. The mean daily NSP intake was 9.8 +/- 4.2 g, with 53% of total daily intake supplied from breakfast meals, whereas noon and evening meals accounted for 30% and 14%, respectively. The results, while suggesting that zinc bioavailability is unlikely to be adversely affected, indicated that dietary fiber intake levels are probably inadequate, particularly in view of the nonambulant condition and low physical activity prevalent in such individuals, who may, as a consequence, be susceptible to health disorders associated with impaired bowel function and constipation.

Adult↗

Association of IL-6 gene alleles with systemic lupus erythematosus (SLE) and with elevated IL-6 expression.

To evaluate the association of alleles of regions having regulatory potential in the IL-6 gene, with SLE, the AT-rich minisatellite in the 3' flanking region and the 5' promoter-enhancer of the IL-6 gene were genotyped by PCR- and RFLP-based methods. The AT-rich minisatellite allele distribution pattern was significantly different in SLE (n = 146) as compared to 139 controls (chi 2(7) = 48.97, P = 0.001, Caucasians; and chi 2(7) = 19.93, P = 0.006, African-Americans). In either race, short allele sizes (< or = 792 bp) were seen exclusively in SLE patients (P = 0.001), whereas the 828-bp allele was over-represented in controls (P = 0.015 and 0.002). In contrast, there was no preferential association of SLE with G/C alleles in the 5' region of the IL-6 gene. Furthermore, our results suggest that the 3' minisatellite alleles have biological significance: (1) B lymphoblastoid cells of patients having one or two SLE-associated alleles secreted IL-6 in 3- to 4-fold higher levels than non-allelic cells (P < 0.05); (2) higher percentages (approximately 4-fold) of IL-6 positive monocytes were observed in individuals having SLE-associated IL-6 alleles; (3) in lupus patients having SLE-associated minisatellite alleles, IL-6 mRNA stability was significantly enhanced.

Adult↗

Large laser sheaths for pacing and defibrillator lead removal.

BACKGROUND AND OBJECTIVE: In a recent clinical trial, the 12-F laser sheath showed 95% success in completely explanting chronically implanted pacing leads smaller than 7.5-F diameter. For larger leads, two new sizes of laser sheath have been implemented, the 14-F and 16-F (outer diameter) devices, which accommodate leads up to 9.5- and 11.5-F, respectively. The object of this study was to determine the cutting ability of the larger devices compared to the 12-F design. MATERIALS AND METHODS: The rate of device advancement through fresh porcine aorta was measured for three sizes of laser sheath as pulsed ultraviolet light from a 308-nm XeCl excimer laser was applied. Dependent variables were fluence (mJ/mm2), laser pulse repetition rate, and pressure applied between the device and the tissue. RESULTS: At 60 mJ/mm2, 40 Hz repetition rate and 1.4 kg/cm2 pressure, all devices produced cutting rates in the range of 9-13 microns/pulse. Improvement in advancement per laser shot can be attained by increasing any independent variable studied. CONCLUSIONS: Physicians must apply only slightly greater force to the larger laser sheaths, and maximum available repetition rate and fluence implies maximum cutting speed.

Animals↗

High-burst-strength, feedback-controlled bipolar vessel sealing.

BACKGROUND: The inherent tedium of intracorporeal knot tying has stimulated greater interest in energy-based and mechanical alternatives for hemostasis. METHODS: Three hundred thirty-one arteries and veins were sealed by application of precisely controlled electrothermal energy and physical pressure, allowing for brief cooling in compression, in experimental animals and fresh abattoir vessels. These seals were compared for bursting strength with occlusions by ultrasonic and bipolar coagulation, surgical clips, and ligatures. RESULTS: Ultrasonic and bipolar occlusions were significantly less likely to have burst strengths greater than 400 mmHg as compared with seals, clips, and ligatures (p < 0.001). Seal competence could be visually assessed by its translucence. CONCLUSIONS: Precise energy control with physical compression, including a brief cooldown, produces a distinctive, translucent seal of partially denatured protein that can typically be transected after a single application. These seals have bursting strengths comparable to those of clips and ligatures and resist dislodgement because they are intrinsic to the vessel wall structure.

Animals↗

A new syndrome of Crohn's disease and pachydermoperiostosis in a family.

Few syndromic associations with Crohn's disease are described. The aim of this study was to characterize a new syndrome of Crohn's disease associated with pachydermoperiostosis in 3 brothers. Three probands, 6 siblings, both parents, 20 of 21 third-generation relatives, and 9 spousal controls were evaluated. Serological evaluation for antineutrophil cytoplasmic antibodies and human leukocyte antigens as well as genetic testing for tumor necrosis factor microsatellites, intercellular adhesion molecule 1 polymorphisms, the interleukin 1 receptor antagonist gene, and the interleukin 1 beta gene were performed. Only the 3 probands were affected and developed pachydermoperiostosis between ages 14 and 17 years. Pachydermoperiostosis preceded Crohn's ileocolitis by 6 and 20 years in two probands, excluding secondary hypertrophic osteoarthropathy. Two probands were antineutrophil cytoplasmic antibody positive vs. 1 of 27 unaffected relatives (P < 0.001, chi 2). Haplotypes for human leukocyte antigen and tumor necrosis factor microsatellites were discordant. The probands' generation was homozygous for the common allele 1 of the interleukin 1 receptor antagonist and interleukin 1 beta genes. Two probands carried a rare polymorphism of the intercellular adhesion molecule 1 gene. A new syndrome of Crohn's disease and pachydermoperiostosis associated with antineutrophil cytoplasmic antibodies is described. Inheritance is most likely autosomal recessive by pedigree. No clear association was found between this syndrome and the gene regions evaluated.

Adolescent↗

Somatostatin receptor subtype expression in human thyroid and thyroid carcinoma cell lines.

Somatostatin (SRIH) analogs can suppress the proliferation of human differentiated thyroid carcinoma cell lines that express SRIH receptors (SSTRs) demonstrated by radioligand binding analysis. Five distinct human SSTR subtypes (hSSTR1-5) that bind native SRIH exhibit diverse affinities to a wide range of SRIH analogs. Reverse transcriptase-PCR amplification of ribonucleic acids (RNAs) obtained from normal thyroid tissues and nine human thyroid carcinoma cell lines, grown as monolayer cultures and xenograft tumors in nude mice, were used to discriminate expression of SSTR subtype messenger RNAs (mRNAs). The cell lines were derived from a follicular adenoma (KAK-1), two follicular carcinomas (MRO-87 and WRO-82), two papillary carcinomas (NPA87 and KAT-10), and four anaplastic thyroid carcinomas (DRO-90, ARO-81, KAT-4, and KAT-18). Most thyroid cancer cell line monolayers and xenografts expressed SSTR3 and SSTR5 mRNAs. SSTR1 expression was more varied between monolayers and xenografts, whereas SSTR2 mRNA was only faintly detectable at the most extreme resolution. SSTR4 mRNA was faintly positive in only one anaplastic carcinoma xenograft. Normal thyroid also expressed SSTR3 and SSTR5 mRNAs, with only faint expression of SSTR1 and SSTR2 mRNAs (in one of five and three of five samples, respectively). SSTR mRNA expression was dependent upon in vitro culture conditions, as xenograft SSTR mRNA expression tended to decrease compared to that in each respective monolayer culture. Characterization of SSTR subtype expression in human thyroid carcinomas may permit targeting of specific SRIH analogs to inhibit proliferation of differentiated and anaplastic thyroid carcinomas in patients.

Animals↗

Antineoplastic activity of taxol against human anaplastic thyroid carcinoma cell lines in vitro and in vivo.

Anaplastic thyroid carcinoma is a rapidly fatal neoplasm that fails to adequately respond to any known chemotherapeutic regimen. We tested taxol (paclitaxel) against six human anaplastic thyroid carcinoma cell lines (DRO-90, ARO-81, KAT-4, KAT-18, SW-1736, and BHT-101). Each cell line monolayer culture, in log phase growth, was treated with taxol concentrations ranging from 0.001-5.0 mumol/L. Cell numbers, after 24-, 48-, and 72-h growth periods in separate experiments, were expressed as percentages of control cell numbers without taxol. All cell lines showed maximal inhibition with 0.05 mumol/L taxol at 3-28% of control cell numbers. Greater inhibition was seen with longer growth periods. Three cell lines (DRO-90, ARO-81, and KAT-4) were grown as sc xenograft tumors in nude mice for 18-26 days. Treatment groups received sc taxol injections in sites distant from the tumors, whereas control mice received vehicle. All taxol-treated xenografts were inhibited to near-starting volume or disappeared, whereas control xenograft volumes increased 9- to 59-fold. These results suggest that taxol may have beneficial clinical effects in anaplastic thyroid carcinoma patients.

Animals↗

Mitochondrial biogenesis in early mouse embryos: expression of the mRNAs for subunits IV, Vb, and VIIc of cytochrome c oxidase and subunit 9 (P1) of H(+)-ATP synthase.

The mouse egg contains about 90,000 mitochondria which undergo a buildup of mitochondrial cristae and increase in respiratory activity during cleavage. The mitochondrial DNA does not replicate during preimplantation development but is transcribed actively from the two-cell stage onward (Pikó and Taylor, 1987: Dev Biol 123:364-374). To gain further insight into mitochondrial biogenesis, we have now determined the steady state amounts of the mRNAs for the cytochrome c oxidase (COX) subunits IV, Vb and VIIc and the H(+)-ATPase subunit 9 (P1) (all encoded by nuclear genes) in slot hybridization experiments of total RNA from oocytes and early embryos. All four mRNAs showed a similar developmental pattern of prevalence, characterized by a steady decline in mRNA copy numbers from the late growth-phase oocyte through the two-cell embryo, and an about 30-fold rise during cleavage through the blastocyst stage. However, the ATPase subunit 9 (P1) mRNA was about three times more prevalent in cleavage-stage embryos than the COX mRNAs. A similar pattern was obtained previously for the mitochondrial-encoded COX I and II mRNAs, but the latter accumulate at a 30-50-fold excess over the nuclear-encoded COX subunit mRNAs during the cleavage stages. The results suggest a coordinated activation and transcription of the mitochondrial and nuclear genes for the components of the respiratory apparatus beginning with the two-cell stage. It is estimated that new respiratory chains are produced at a rate of 50-100 chains hr-1/mitochondrion in the early blastocyst, accounting for 3.5-7% of the total protein synthetic activity at this stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pressure tuning infrared spectroscopic study of cisplatin-induced structural changes in a phosphatidylserine model membrane.

The dynamic effect of cis-diamminedichloroplatinum(II) (DPP) and its aquated metabolite (DDP-OH) on a dimyristoylphosphatidylserine (DMPS) model membrane was investigated by pressure tuning vibrational spectroscopy. The native species (DDP-Cl) and the aquated species (DPP-OH) were both observed to bind to the carboxylate group of the serine as evidenced by a frequency shift of 1622-1620 cm-1. However, only DDP-OH was observed to bind to the phosphate group (PO(-)2). The binding of either drug to DMPS resulted in an increased pressure required to halt the reorientational fluctuations of the acyl chains, indicating that the distance between the chains were increased. The two drugs did not partition into the matrix of the hydrophobic section in the model membrane. Collectively, these data suggest that DDP-Cl and DDP-OH are capable of binding to the polar head group of DMPS, resulting in an enlargement of the area of the head and a subsequent increase in the intermolecular distance between the acyl chains.

Antineoplastic Agents↗

Cisplatin and radiation in the treatment of tumors of the central nervous system: pharmacological considerations and results of early studies.

PURPOSE: To review the human central nervous system pharmacology of cisplatin, factors that affect cisplatin uptake in tumors, and use alone and with radiation for the treatment of primary brain tumors. METHODS AND MATERIALS: The authors review their own prior published and unpublished experience and data published by other groups on the above issues. RESULTS: Cisplatin is one of the most active chemotherapy drugs available for the treatment of solid tumors. It is synergistic with several other agents, including radiation. While it attains only low concentrations in the normal central nervous system, concentrations and plasma-tissue transfer constants for human intracerebral tumors are comparable to those in extracerebral tumors. Tumor type appears to be a more important determinant of platinum concentration than is tumor location, and gliomas do achieve lower concentrations than do other intracerebral or extracerebral tumors. Several other factors have also been identified that correlate with concentrations of cisplatin achieved in human tumors. While cisplatin alone and in combination with other drugs does have some degree of efficacy against primary brain tumors, combining it with cranial irradiation has generally not resulted in any substantial improvement in outcome to date, although some individual studies have been somewhat encouraging. New approaches are currently under investigation. CONCLUSION: Human pharmacology studies provide a rationale for use of cisplatin in the treatment of human brain tumors, and human and in vitro studies suggest some manipulations that might potentially further augment tumor platinum concentrations. While clinical studies suggest that cisplatin combinations may be of some value vs. human primary brain tumors and brain metastases, and while in vitro studies suggest that cisplatin potentiates radiation efficacy, no combination of cisplatin plus radiation yet tested has appeared to be superior to radiation alone.

Brain Neoplasms↗

Somatostatin analogs affect proliferation of human thyroid carcinoma cell lines in vitro.

Antiproliferative effects of somatostatin (SRIH) analogs were investigated in human thyroid carcinoma cell lines. Membrane preparations from six human thyroid cell lines, including follicular (RO 87-M-1 and RO 82-W-1), papillary (NPA87), and anaplastic (RO 90-D-1) carcinomas, a follicular adenoma, as well as benign and malignant human thyroid tissues, contained high affinity SRIH-binding sites. Ligand-binding studies ([125I]Tyr11-SRIH) demonstrated mean dissociation constants ranging from 114-224 pmol/L, and 20-154 fmol/mg membrane protein mean receptor sites, in cell lines. Four cell lines were grown for 3 days in monolayers with SRIH analogs (octreotide or MK0678) at concentrations from 0.05-100 nmol/L in serum-free medium to assess changes in cell numbers. At the highest dose, MK0678 produced dose-dependent inhibition of growth in RO 87-M-1 and NPA87, each to about 70% of that in control cells. Octreotide produced dose-dependent stimulation of growth in RO 87-M-1 cells, but caused growth inhibition in NPA87 cells, with loss of effect at the highest dose. RO 82-W-1 did not respond to MK0678, yet caused biphasic inhibition with octreotide (75% and 45% of control cell numbers at 0.05 and 100 nmol/L doses, respectively). Anaplastic cells, RO 90-D-1, did not respond to either analog despite similar ligand binding. Addition of epidermal growth factor (100 micrograms/L) or TSH (200 mU/L) increased the sensitivity of RO 87-M-1 cells to growth inhibition by the lowest dose of MK0678, producing biphasic dose-response curves. In conclusion, the present data demonstrate specific SRIH binding to membranes of thyroid carcinoma cells and tissues as well as discordant growth effects of different SRIH analogs on the same cell lines. This may be a result of differential stimulation and regulation of distinct SRIH receptor subtypes.

Carcinoma↗

Expression of ribosomal protein genes in mouse oocytes and early embryos.

The quantitative changes in the mRNAs for ribosomal proteins L7a, L18a, and S15 were assayed in slot hybridization experiments using labeled cRNA probes with total RNA from late growth-phase oocytes, ovulated eggs, and early embryos through the blastocyst stage. All three mRNAs showed a similar developmental pattern of prevalence, but their copy numbers per oocyte or embryo fluctuated according to developmental stage. There are on an average about 17,000 copies of each mRNA in the late growth-phase oocyte; this number drops to one-fifth to one-tenth in the ovulated egg and two-cell embryo but increases rapidly during cleavage to bout 25,000 in the eight-cell embryo and about 42,000 in the blastocyst. A comparison of the levels of these mRNAs with the reported rates of ribosomal protein synthesis (LaMarca and Wassarman, 1979) suggests that, in late growth-phase oocytes, ribosomal protein synthesis is regulated primarily at the translational level and is kept low by some factor limiting mRNA utilization. On the other hand, the high rate of ribosome biosynthesis during early embryogenesis from the two-cell stage onward appears to involve the coordinate activation and transcription of ribosomal RNA and ribosomal protein genes coupled with the immediate translational utilization of ribosomal protein mRNAs.

Animals↗

Improved method for i.r. determination of the degree of N-acetylation of chitosan.

Three published i.r. absorption band ratios for determining the % N-acetylation of chitosan have been used to follow the rate of alkaline deacetylation of chitin. Only one, the A1655/A3450 ratio, gives the expected rate of deacetylation curve. Consideration of the various i.r. ratios has led to a new relationship, % N-acetylation = (A1655/A3450) x 115, where the absorbance of the amide I band at approximately 1655 cm-1 is determined using the baseline proposed previously. The values obtained using this proposed relationship agree closely with those obtained from dye adsorption measurements for chitosans having % N-acetylation values in the range 0-55%.

Acetylation↗

Expression of the rig gene in mouse oocytes and early embryos.

A clone selected from a two-cell mouse embryo cDNA library has been sequenced and identified as rig cDNA. The rig gene codes for a highly conserved nuclear protein, which may have a general role in cell growth or replication (Shiga et al.: Proc Natl Acad Sci USA 87:3594, 1990). The quantitative changes in rig mRNA were studied in blot hybridization experiments with total RNA from oocytes and early embryos. The amount and relative abundance of rig mRNA change considerably during early development. There are about 1.6 x 10(4) rig mRNA molecules in a late growth-stage oocyte; this number is reduced to about one-tenth in the ovulated egg but increases about twenty-fold during cleavage through the blastocyst stage. In F9 embryonal carcinoma cells, the relative abundance of rig mRNA is similar to that in blastocysts (about 0.1% of the mRNA population), but it is about eight-fold higher in the mouse myeloma cell line MOPC-104E. The high level of rig mRNA in late growth-stage oocytes suggests that the rig gene product may be important for overall transcriptional activity rather than DNA replication and mitosis. Alternatively, the rig protein may be a storage product of oogenesis and have a role in the initiation of development.

Amino Acid Sequence↗

Iron status in a group of long-stay mentally handicapped menstruating women: some dietary considerations.

As part of a longitudinal study aimed at assessing the dietary intakes and nutritional status of a group of long-stay mentally handicapped subjects, 15 women of menstruating age were considered for a substudy to assess the influence of intake levels of dietary iron, energy, tea, coffee and vitamin C on their iron status. The assessment comprised a week-long weighed dietary survey and the measurement of a number of haematological indices that included serum ferritin concentration. Information on duration of menses was also collected and included in the assessment. Two-fifths of the subjects assessed had a serum ferritin concentration less than 12 micrograms/l indicating iron deficiency, including one who was considered anaemic as suggested by a haemoglobin level less than 12 g/dl. Duration of menses showed a negative significant correlation with serum ferritin concentration. The mean iron intake in the group was 9.5 +/- 1.5 mg/day. Energy intakes were low and positively correlated with iron intake. Although serum ferritin showed no correlation with iron intake, it showed significant negative correlations with the daily and meal-time intakes of tea and a significant positive correlation with the meal-time intakes of vitamin C. The six iron-depleted subjects were assessed as a separate group (Group I) in comparison with the other nine subjects who had a serum ferritin concentration greater than 12 micrograms/l. The results of this assessment showed that, while there were no significant differences in duration of menses or the mean daily intakes of iron and energy between the two groups. Group I subjects had significantly higher daily and meal-time intakes of tea and significantly lower meal-time intakes of vitamin C compared to Group II subjects. The study provides some evidence suggestive of an association between the iron deficiency states observed and tea intake in adversely affecting iron status, particularly in the absence of adequate meal-time intakes of vitamin C. The findings from the study also suggest that long-stay mentally handicapped women of menstruating age, in addition to their handicap and dependency states which may often predispose them to a low dietary intake, are at particular risk of iron deficiency.

Adult↗