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Biomedical subjects

K Taylor

Publications and source records attributed to K Taylor.

At least 163 records · Page 9Linked to original sources

Quantitative and qualitative differences in growth, invasion and lung colonization of an anaplastic and a papillary human thyroid cancer cell line in vitro and in vivo.

Invasion and metastasis remain major reasons for failure of anti-cancer therapy. Cell lines derived from human carcinomas are frequently used to investigate the molecular mechanisms that underlie invasion and metastasis. Unfortunately many of these cell lines do not retain the malignant characteristics of their parental tumors. We therefore conducted a series of experiments in vivo and in vitro to identify which aspects of malignancy of a papillary (NPA'87) and an anaplastic (DR090-1) thyroid carcinoma were consistent with the pathology of the parental tumor types. We evaluated tumor growth, invasion and metastasis of DRO90-1 and NPA'87 in vivo following inoculation of the tumor cells under the dermis, under the renal capsule and into the lateral tail vein of nude mice. This evaluation in vivo showed that the anaplastic carcinoma had a faster growth rate compared with the papillary carcinoma. Furthermore, the papillary carcinoma cells could destroy and infiltrate surrounding tissue but were not capable of extravasation and colonization of lung tissue. The anaplastic cells formed lung nodules following injection into the tail vein of nude mice. This lung colonizing capability of DRO90-1 correlated with their capacity to secrete an active 62 kDa gelatinase and to migrate through reconstituted basement membrane in vitro.

Animals↗

High-resolution fluorescence in situ hybridization of RBM- and TSPY-related cosmids on released Y chromatin in humans and pygmy chimpanzees.

Applying two-colour fluorescence in situ hybridization (FISH) we simultaneously hybridized RBM- and TSPY-related cosmids to Y chromosomes in prophase and to released Y chromatin in interphase nuclei of man and pygmy chimpanzee. Whereas, even on prophasic Y chromosomes, no resolution of the overlapping RBM and TSPY signal clusters could be achieved, the RBM and TSPY signals are completely separated from each other in our maximum released Y chromatin stretches in interphase nuclei. These results unequivocally lend support to the view that the RBM and TSPY families have an interspersed organization on the Y chromosomes of man and higher apes. Thus, the distribution of RBM and TSPY signals might well go back to a common organization of these genes next to each other on an ancient Y chromosome.

Animals↗

Degeneracy in human multicopy RBM (YRRM), a candidate spermatogenesis gene.

In order to search for mutations in the multicopy RBM genes that might be associated with male infertility, we have used sequence data from the reported cDNA clone to determine the intron exon boundaries of the YRRM 1 gene. This gene has 12 exons, three of which encode the putative RNA binding domain of the protein. Different copies of the gene contain sequence variations and, additionally, give rise to transcripts with different numbers of copies of the repeated SRGY motif. Since mutations in the RNA binding domain would seem likely to have an effect on the activity of the protein, we have scanned these exons for mutations by SSCP on DNA from normal and infertile men. Sequence differences in the exon encoding the N-terminal part of the RNA binding domain account for at least four different classes of the gene and give rise to different SSCP conformers. Sequence analysis shows that one of these classes is a pseudogene and that the members of another class are nonfunctional. RT-PCR shows that all classes are transcribed and that the A class is most abundant. We have found a point mutation that alters the highly conserved RNP2 motif in one infertile patient. This mutation is also found in his father. We have used PCR followed by SSCP analysis to map RBM on a Y Chromosome (Chr) YAC contig and have demonstrated a distribution that spans a major part of this chromosome's euchromatin.

Amino Acid Sequence↗

High response rates with short infusional 2-chlorodeoxyadenosine in de novo and relapsed low-grade lymphoma. Australian and New Zealand Lymphoma Study Group.

Thirty-five patients (eight de novo, 27 relapsed disease) with low-grade non-Hodgkin's lymphoma (diffuse small lymphocytic, follicular small cleaved cell, follicular mixed cell, and lymphoplasmacytoid) were treated with 2-chlorodeoxyadenosine (2CdA) at a daily dose of 0.14 mg/kg for 5d (2 h infusion) for an average of three cycles. Minor treatment delays, generally due to haematological toxicities, occurred in nine of 105 cycles. Major toxicities were lymphopenia, neutropenia and thrombocytopenia. Opportunistic infections occurred in seven patients. Overall response rate was 69% (five complete, 19 partial) reaching 88% for de novo patients (two complete, five partial). Elevated beta 2-microglobulin level was negatively predictive of response (P = 0.0014). Eight of 24 responders relapsed, with a median follow-up of 13 months. 2CdA administered as an intermittent infusion shows considerable single-agent activity in low-grade lymphomas achieving high response rates of prolonged duration. Consideration of schedules where 2CdA is alternatively administered with combination chemotherapy appears warranted.

Adult↗

Protein inheritance: lambda plasmid replication perpetuated by the heritable replication complex.

BACKGROUND: Replication of a plasmid derived from the Escherichia coli phage lambda initiates by binding of the lambda O protein initiator to the origin of lambda DNA replication, ori lambda. The lambda P protein participates in subsequent steps of assembly of the lambda replication complex. A function of lambda P required for replication complex assembly is inactivated at 43 degrees C by the ts1 mutation. RESULTS: We found that the lambda replication complex assembled at 30 degrees C survives the temperature upshift in lambda crotsPts1 plasmid-harbouring bacteria. We present several lines of evidence that in this system (in which the replication complex assembly does not occur), the replication complex assembled prior to the temperature upshift is inherited by one of two daughter plasmid copies at each replication round for more than 30 cell generations. The 'old' replication complex-driven replication is chloramphenicol-resistant and rifampicin-sensitive. This replication is dependent on lambda O and host dnaK, dnaJ and grpE chaperone gene functions. CONCLUSIONS: The lambda O-containing replication complex is inherited together with DNA and bears information how to initiate the next round of replication at ori lambda; thus, we consider that this phenomenon deserves to be called protein inheritance.

Bacterial Proteins↗

The role of anti-variable surface glycoprotein antibody responses in bovine trypanotolerance.

It has been reported that some breeds of cattle such as the N'Dama mount a more effective antibody response to the variable surface glycoprotein coat of trypanosomes and that this may contribute to their ability to control the infection. Thus we have investigated antibody responses to surface exposed epitopes of the variable surface glycoprotein in Trypanosoma congolense-infected N'Dama (trypanotolerant) and Boran (susceptible) cattle. Similar titres and isotypes were found in both N'Damas and Borans indicating that trypanotolerance is not associated with superior antibody-mediated destruction of trypanosomes. However, significant differences in antibody responses to cryptic VSG epitopes and non-trypanosome antigens were identified. Trypanosusceptible Boran cattle had low IgG1 responses to cryptic epitopes but high IgM responses to non-trypanosome antigens such as beta-galactosidase. In contrast the N'Dama cattle had significantly higher IgG1 responses to cryptic VSG epitopes and negligible responses to beta-galactosidase. These results indicate differences in the induction of anti-trypanosome immune responses between trypanotolerant and susceptible cattle infected with T. congolense.

Animals↗

High-dose versus low-dose valproic acid as a prophylactic medication.

Valproic acid has been shown to be effective in migraine prophylaxis. Its method of action is believed to be the inhibition of gamma-aminobutyric acid transaminase. The therapeutic dose needed to prevent migraine headaches has been examined in several studies, yet the optimum dose has not been found. In this case report, valproic acid was given to a 24-year-old woman with chronic headaches at 1000 mg per day. Her headaches resolved for 2 months. She tapered herself off of the medication, and her headaches returned. She was restarted at 500 mg per day of valproic acid and again, her headaches resolved. She preferred being on the lower dose which she found as effective as the higher dose. Her case makes two interesting points. The first is that lower dosages of valproic acid may be as effective as higher ones in headache prophylaxis. The second is that more studies looking at dose ranges are needed to correlate effectiveness with daily requirements.

Adult↗

Mapping the human Y chromosome by fingerprinting cosmid clones.

We have used Y-specific cosmid clones in a random fingerprinting approach to build contigs on the human Y chromosome. Clones derived from two libraries have been analyzed. The construction of one library is described here, the second was the Y chromosome-specific library LLOYNCO3 "M" (Lawrence Livermore National Laboratory). To date, we have fingerprinted 4430 cosmids: 377 contigs have been constructed containing from 2 to 39 clones. Along with the singletons, we estimate that we have covered 72.5% of the euchomatic portion of the Y chromosome with fingerprinted clones. Sequence tagged sites are being used to anchor cosmids and contigs onto the YAC framework.

Base Sequence↗

Nitric oxide synthesis is depressed in Bos indicus cattle infected with Trypanosoma congolense and Trypanosoma vivax and does not mediate T-cell suppression.

Infection with African trypanosomes causes the diseases sleeping sickness in humans and nagana in cattle in sub-Saharan Africa. Suppression of cellular immune responses is a feature of trypanosomiasis in bovine, human, and murine hosts. Some aspects of immunosuppression in the murine model are mediated by nitric oxide (NO) produced by gamma interferon (IFN-gamma)-activated macrophages. We have investigated whether a similar mechanism is responsible for T-cell unresponsiveness in bovine trypanosomiasis. Bovine monocytes and macrophages from uninfected cattle and activated in vitro with IFN-gamma produced NO; however, this response was down-regulated in infected cattle. Similarly, the expression of inducible NO synthase messenger RNA was depressed in macrophages of infected cattle. Proliferation of mononuclear cells of trypanosome-infected cattle cultured with mitogen or trypanosome antigens was unchanged by the addition of an NO synthase inhibitor. Lymphocytes of infected cattle secreted interleukins with T-cell growth factor activity after in vitro activation with mitogens but not after activation with trypanosome antigens. Although lymph node cells secreted IFN-gamma after in vitro activation, ex vivo expression of mRNA was depressed. In contrast, the level of expression of interleukin 10 mRNA was higher during infection. We conclude that NO is not involved in the loss of T-cell proliferative function associated with trypanosomiasis in cattle and that, in contrast to the mouse model, the capacity of monocytes and macrophages to produce NO is actually down-regulated in infected cattle.

Animals↗

The cbpA chaperone gene function compensates for dnaJ in lambda plasmid replication during amino acid starvation of Escherichia coli.

We found previously that lambda plasmid DNA replication in amino acid-starved Escherichia coli relA mutants (i.e., during the relaxed response), which is carried out by the inherited replication complex, is dependent on functions of DnaK and GrpE molecular chaperones but proceeds in a dnaj mutant at a nonpermissive temperature. Here we demonstrate that this replication is inhibited when functions of both dnaJ and cbpA are impaired. In complete media, the growth of the lambda pi A66 phage (capable of replicating in E. coli dnaJ, dnaK, and grpE missense mutants at 30 degrees C), as well as efficiency of transformation by the lambda pi A66 plasmid, is significantly decreased in a dnaJ259 cbpA::kan double mutant. These results strengthen the proposal of other authors (C. Ueguchi, M. Kakeda, H. Yamada, and T. Mizuno, Proc. Natl. Acad. Sci. USA 91:1054-1058, 1994; C. Ueguchi, T. Shiozawa, M. Kakeda, H. Yamada, and T. Mizuno, J. Bacteriol. 177:3894-3896, 1995; and T. Yamashino, M. Kakeda, C. Ueguchi, and T. Mizuno, Mol. Microbiol. 13:475-483, 1994) that the cbpA gene product is a functional analog of the DnaJ chaperone in E. coli.

Amino Acids↗

A rapid method for emergency ring removal.

Injuries caused by embedded rings are extremely rare. Swelling can lead to decreased circulation and can threaten the viability of involved fingers. Skin changes can become chronic, as when rings are left on fingers of patients with decreased mentation or sensation. In this report, the authors discuss a technique for removal of embedded rings from the fingers of a schizophrenic patient.

Constriction, Pathologic↗

In vitro biomechanical comparison of the strength of the linea alba of the llama, using two suture patterns.

OBJECTIVE: To compare the strength of the sutured linea alba, in vitro, using 2 suture patterns. ANIMALS: 12 clinically normal llamas. PROCEDURE: 2 incisions in the linea alba of 12 llamas were closed with a simple continuous or inverted cruciate pattern, and tissue was harvested after 10 days. In 6 llamas the simple continuous line was intact; the inverted cruciate specimens contained 6 sutures. In 6 llamas, 1 knot was excised in the simple continuous pattern to simulate a failed line; the cruciate pattern contained 5 knots. Tissue sections were taken from cranial, between, and caudal to the linea alba incisions to compare fascial thickness. The sutured specimens were mounted in a mechanical testing system and tested to failure. A mixed-model ANOVA was used to evaluate the effects of suture pattern and incisional position on mechanical properties. RESULTS: Significant differences were not found between suture patterns or between location for yield force, failure force, or yield strain, whereas failure strain was lower for the intact simple continuous pattern than the inverted cruciate pattern (P = 0.003). From histomorphometric analysis, the caudal tissue specimens were significantly thinner than the middle tissue specimen cranial to the umbilicus (P = 0.006). CONCLUSION: There was no significant difference in monotonic breaking strength of the linea alba sutured with the simple continuous or inverted cruciate pattern. CLINICAL RELEVANCE: These results justify the use of the simple continuous pattern over the cruciate pattern for ventral midline closure in llamas because of the ease of placement and speed.

Abdominal Muscles↗

Regulation of milk lipid secretion: effects of oxytocin, prolactin and ionomycin on triacylglycerol release from rat mammary gland slices.

A system for the study of the regulation of the release of triacylglycerols by mammary gland slices was developed. By prelabelling the triacylglycerol pool with [3H]oleate measurements of release of both mass of triacylglycerol and of newly synthesized triacylglycerol have been made. Oxytocin and ovine prolactin stimulated release of triacylglycerol and protein, but the former was 40-fold more effective. Recombinant bovine prolactin was even less active than ovine prolactin, suggesting that contamination of the latter with oxytocin and/or vasopressin was partly responsible for its stimulatory effect on release. The findings support the view that the major effect of oxytocin is to stimulate contraction of myoepithelial cells and thus release secreted lipid stored in the lumen of the mammary gland alveoli. Ionomycin, a Ca2+ ionophore, also stimulated lipid release, but probably not by the usual apocrine route. Parathyroid hormone-related protein, a peptide produced by the mammary gland, did not stimulate release or antagonize the effects of oxytocin. Release of lipid was also measured in mammary gland slices from late-pregnant, early- and mid-lactating rats and lactating rats made prolactin-deficient. Hormonal stimulation in vitro showed the maturation of response seen in vivo on transition from late pregnancy to peak lactation. Prolactin deficiency resulted in decreased release of newly synthesized lipid in response to oxytocin.

Animals↗