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Biomedical subjects

R A White

Publications and source records attributed to R A White.

At least 37 records · Page 2Linked to original sources
PubMed2001

Synergistic inhibition of human lung cancer cell growth by adenovirus-mediated wild-type p53 gene transfer in combination with docetaxel and radiation therapeutics in vitro and in vivo.

Chemotherapy given sequentially or concurrently with external beam radiation therapy has emerged as a standard for the treatment of locally advanced lung cancer. Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro, in animal models, and in human clinical trials. However, no information is available on the combined effects of p53 gene transfer, chemotherapy, and radiation therapy on lung cancer growth in vitro and in vivo. Therefore, we developed two-dimensional and three-dimensional isobologram modeling and statistical methods to evaluate the synergistic, additive, or antagonistic efficacy among these therapeutic agents in human non-small cell lung cancer cell lines A549, H460, H322, and H1299, at the ID50 and ID80 levels. The combination of these three therapeutic agents exhibited synergistic inhibitory effects on tumor cell growth in all four cell lines at both the ID50 and the ID80 levels in vitro. In mouse models with H1299 and A549 xenografts, combined treatment synergistically inhibited tumor growth in the absence of any apparent increase in toxicity, when compared with other treatment and control groups. Together, our findings suggest that a combination of gene therapy, chemotherapy, and radiation therapy may be an effective strategy for human cancer treatment.

Adenoviridae↗
PubMed2000

Management of inflammatory polyps in 37 cats.

The case records of 37 cats treated for nasopharyngeal or aural inflammatory polyps were reviewed. Thirty of them were managed conservatively with the polyp being removed by traction alone. Long-term follow-up information was available for 22 cats, of which 13 (59 per cent) had no recurrence of clinical signs. The remaining nine cats required recurrent polyps to be removed surgically. Cats with only nasopharyngeal polyps were nearly four times more likely to be cured by traction alone than cats with aural polyps, and none of the cats that was treated with prednisolone after traction suffered a recurrence. Cats with more severe aural signs were more likely to require surgery.

Animals↗
PubMed2000

Squamous cell carcinoma of the nasal planum in 17 dogs.

Squamous cell carcinoma of the nasal planum was diagnosed in 17 dogs over a period of 11 years. Ulceration, bleeding and sneezing were the most common clinical signs. One dog had cytological evidence of metastasis to the local lymph node. The dogs were treated by surgical resection, fractionated megavoltage irradiation, or a combination of the two. Surgical resection gave the most favourable results; four of six dogs were cured but a recurrence of the tumour was predicted in the other two on the basis of incomplete or marginal resection. Radiotherapy alone was not as effective; one of four dogs was cured, and the tumour recurred in the others within 24 weeks (median eight weeks). Combined surgical resection and radiotherapy did not produce a cure in any of the seven remaining dogs, and the tumour recurred within 12 weeks (median nine weeks). Three dogs had cytological evidence of lymph node metastasis when the tumour recurred. The dogs' prognosis was adversely affected by the interval between their initial examination and treatment, but there was no apparent association between the histological grade of the tumour and the clinical outcome.

Animals↗
PubMed2000

Genomic organization, chromosomal localization and regulation of expression of the neuronal nuclear matrix protein NRP/B in human brain tumors.

The nuclear matrix and its role in cell physiology are largely unknown, and the discovery of any matrix constituent whose expression is tissue- and/or cell-specific offers a new avenue of exploration. Studies of the novel neuronal nuclear matrix protein, NRP/B, reveal that it is an early and highly specific marker of neuronal induction and development in vertebrates, since its expression is restricted mainly to the developing and mature nervous system. These studies also show that NRP/B is involved in neuronal differentiation. To further examine the structure-function of NRP/B, we have cloned and characterized the murine Nrp/b gene. The murine gene consists of four exons interrupted by three introns that span 7.6kb of DNA. The complete open reading frame is localized in exon 3, suggesting that NRP/B is highly conserved during evolution. Chromosomal analysis shows that NRP/B is localized to chromosome 13 in mouse and chromosome 5q12-13 in human. Since our previous studies demonstrated that NRP/B is expressed in primary hippocampal neurons but not in primary astrocytes, we have characterized NRP/B mRNA and protein expression in various brain cell lines and in human brain tumors. Abundant expression of NRP/B mRNA and protein was observed in human neuroblastoma cell lines (IMR32, SKN-MC, SKN-SH), in glioblastoma cell lines (A172, T98G, U87-MG, U118-MG, U138-MG, and U373-MG), in neuroglioma (H4) and astrocytoma cell lines (CCF-STTG1 and SW1088). Confocal analysis of NRP/B in U87-MG glioblastoma cells indicated nuclear localization of NRP/B. NRP/B expression was also observed in human primary brain tumors including glioblastoma multiformae and astrocytomas (total of five cases). These results suggest that NRP/B expression is upregulated in human brain tumors including glioblastomas and astrocytomas, while under normal conditions NRP/B expression is restricted to neurons. This study implicates a role for NRP/B in brain tumor development.

Animals↗
PubMed2000

Simultaneous estimation of T(G2+M), T(S), and T(pot) using single sample dynamic tumor data from bivariate DNA-thymidine analogue cytometry.

BACKGROUND: Estimating the duration of S phase (T(S) ) and the potential doubling time (T(pot) ) from a single time measurement of the movement of cells using bivariate cytometry is common. However, these estimates require an assumption of the duration of G2 + M (T(G2+M) ). Inspection of the measured dynamic quantities, relative movement [RM(t)], fractions of labeled divided and undivided cells (f(lu)(t) and f(ld)(t)) suggests that T(G2+M), T(S), and T(pot) can be determined simultaneously. METHODS: An equation connecting the growth of the cell population, time, and the dynamic quantities was determined. The equation cannot be solved analytically, but accurate approximations can be used to find T(pot). From this result, the value of T(G2+M) can be determined from f(ld)(t), and T(S) can be determined from RM(t). RESULTS: Kinetic parameters obtained from single time estimates using the new method compared to those obtained from the analysis of multiple time-point measurements of MCa-K and MCa-4 murine tumors are shown to be in close agreement. Moreover, estimates of T(G2+M) in MCa-4 tumors, treated with paclitaxel, provide extra information on the changes in T(G2+M). When applied to the rat R3327-G prostate tumor model following androgen ablation, a correlation analysis of the T(pot) values obtained by the new and previous single time-point methods demonstrates that the rank order from shortest to longest T(pot) values are largely preserved. CONCLUSIONS: The new procedure makes direct estimation of T(G2+M) possible from single time-dynamic measurements. The results from previous studies on T(S) and T(pot) are largely unchanged, but extra information is now available.

Adenocarcinoma↗
PubMed2000

GFP-centrin as a marker for centriole dynamics in living cells.

A long-standing puzzle in cell biology is the question of how cells generate one and only one new centrosome in each cell cycle and what is the role of the centriole pair in this process. In this study, the introduction of GFP-centrin into cultured cells allows direct visualization of centriole behavior in living cells and in real time. Using this method, centriole dynamics can be observed throughout the cell cycle and following a variety of experimental treatments. Our studies demonstrate that the biogenesis of new centrioles from individual members of a preexisting centriole pair is asynchronous: the older centriole initiates assembly of a new daughter centriole before the younger centriole initiates assembly of its daughter.

Calcium-Binding Proteins↗
PubMed2000

The design and analysis of a homeotic response element.

We have shown that the 26 bp bx1 element from the regulatory region of Distal-less is capable of imposing control by the homeotic genes Ultrabithorax and abdominal-A on a general epidermal activator in Drosophila. This provides us with an assay to analyze the sequence requirements for specific repression by these Hox genes. Both the core Hox binding site, 5'-TAAT, and the adjacent EXD 5'-TGAT core site are required for repression by Ultrabithorax and abdominal-A. The Distal-less bx1 site thus fits with the model of Hox protein binding specificity based on the consensus PBX/HOX-family site TGATNNAT[g/t][g/a], where the key elements of binding specificity are proposed to lie in the two base pairs following the TGAT. A single base pair deletion in the bx1 sequence generates a site, bx1:A(-)mut, that on the consensus PBX/HOX model would be expected to be regulated by the Deformed Hox gene. We observed, however, that the bx1:A(-)mut site was regulated predominantly by Sex combs reduced, Ultrabithorax and abdominal-A. The analysis of this site indicates that the specificity of action of Hox proteins may depend not only on selective DNA binding but also on specific post-binding interactions.

Animals↗
PubMed2000

Structure, expression, and chromosomal localization of the mouse Atox1 gene.

Copper trafficking in eukaryotes involves small proteins termed metallochaperones, which mediate copper delivery to specific intracellular sites. Previous studies in yeast and human cell lines have suggested that Atox1 plays a critical role in copper delivery to the secretory pathway. In the present study, a mouse Atox1 (mAtox1) cDNA was cloned and shown to encode an open reading frame with 85% amino acid identity to human Atox1. RNA blot analysis revealed that mAtox1 was expressed as a single transcript in multiple tissues, and immunoblotting indicated that the relative abundance of mAtox1 mRNA directly correlated with mAtox1 protein. Analysis of the mAtox1 gene locus revealed a genomic structure with four exons encompassing a total of 14.5 kb. RFLP and haplotype analyses indicated that the mAtox1 locus was tightly linked to the Trhr and D15Bir7 loci on mouse chromosome 15. Taken together, these data reveal marked evolutionary conservation of Atox1 structure and provide a genomic organization and localization that will aid in the genetic deciphering of the molecular role of this protein in copper homeostasis.

Amino Acid Sequence↗
PubMed2000

Prostatic surgery in the dog.

Prostatic diseases are commonly encountered in the dog and a significant proportion of these will require some form of surgical intervention for their successful resolution. The previous perception of the prostate as an obscure pelvic organ coupled with a range of heretofore complex and unsatisfactory surgical techniques have deterred many surgeons from attempting surgical intervention. The recent introduction of omentalization techniques for the management of prostatic infections and secretory abnormalities, which require only modest surgical expertise, has now provided simple solutions for all benign parenchymal diseases. However, neoplastic disease remains a difficult disease both to diagnose and manage.

Animals↗
PubMed2000

Aneurysm rupture after endovascular repair using the AneuRx stent graft.

OBJECTIVE: The purpose of this study was to determine the cause and frequency of aneurysm rupture after endovascular aneurysm repair. METHODS: We reviewed each patient who sustained aneurysm rupture among all patients enrolled for endovascular aortic aneurysm repair in phases I, II, and III of the US AneuRx Multicenter Clinical Trial from June 1996 through October 1999. RESULTS: A total of 1067 patients were enrolled for endovascular aneurysm repair. The AneuRx stent graft was successfully implanted in 1046 patients (98%). Endovascular repair was unsuccessful in 21 patients (2%); 13 patients (1%) were converted to open aneurysm repair. Among these, two patients (0.2%) sustained aneurysm rupture due to procedure-related instrumentation and underwent open surgical conversion. Aneurysm rupture has occurred in seven patients (0.7%) 3 weeks to 24 months (mean, 16 months) after successful endovascular repair. Four patients survived open surgical repair, and three patients died within 30 days. Overall rupture-related mortality was 0.5% and included late deaths after rupture. Before rupture, two patients had endoleak and aneurysm enlargement, and five patients had no endoleak and no aneurysm enlargement. After aneurysm rupture all seven patients had evidence suggesting that there was poor fixation of the stent graft at the proximal distal, or iliac junction fixation sites. The two patients with endoleak declined recommended open surgical or endovascular repair, which could have prevented aneurysm rupture. In retrospect, the five patients without endoleak could potentially have avoided rupture with better patient selection, better stent graft positioning, or reinforcement of fixation points with stent graft extenders. The probability of no aneurysm rupture for all patients undergoing endovascular repair is 0.996 +/- 0.002 at 1 year and 0.974 +/- 0.011 at 2 years by life table analysis with the longest follow-up of 41 months. CONCLUSION: The early risk of aneurysm rupture after endovascular aneurysm repair is low. However, the possibility of rupture persists even in patients with no endoleak after the procedure. Therefore, all patients treated with endovascular aneurysm repair should continue to be monitored after the procedure. Patients with evidence suggesting insecure stent graft fixation should undergo further endovascular treatment or open surgical repair.

Aged↗
PubMed2000

Endoleak as a predictor of outcome after endovascular aneurysm repair: AneuRx multicenter clinical trial.

OBJECTIVE: The purpose of this study was to determine whether evidence of blood flow in the aneurysm sac (endoleak) is a meaningful predictor of clinical outcome after successful endovascular aneurysm repair. METHODS: We reviewed all patients in Phase II of the AneuRx Multicenter Clinical Trial with successful stent graft implantation and predischarge contrast computed tomographic (CT) imaging. The clinical outcome of patients with evidence of endoleak was compared with the outcome of patients without evidence of endoleak. The CT endoleak status before hospital discharge at 6, 12, and 24 months was determined by each clinical center as well as by an independent core laboratory. Endoleak status at 1 month was assessed with duplex scanning examination or CT at each center without confirmation by the core laboratory. RESULTS: Centers reported endoleaks in 152 (38%) of 398 patients on predischarge CT, whereas the core laboratory reported endoleaks in 50% of these patients (P <.001). The center-reported endoleak rate decreased to 13% at 1 month. Follow-up extended to 2 years (mean, 10 +/- 4 months). One patient had aneurysm rupture and underwent successful open repair at 14 months. This patient had a Type I endoleak at discharge but no endoleak at 1 month or at subsequent follow-up times. There were no differences between patients with and patients without endoleak at discharge in the following outcome measures: patient survival, aneurysm rupture, surgical conversion, the need for an additional procedure for endoleak or graft patency, aneurysm enlargement more than 5 mm, the appearance of a new endoleak, or stent graft migration. Despite a higher endoleak rate identified by the core laboratory, neither the endoleak rate reported by the core laboratory nor the endoleak rate reported by the center at discharge was significantly related to subsequent outcome measures. Patients with endoleak at 1 month were more likely to undergo an additional procedure for endoleak than patients without endoleaks. Patients with Type I endoleaks at discharge and patients with endoleak at 1 month were more likely to experience aneurysm enlargement at 1 year. However, there was no difference in patient survival, aneurysm rupture rate, or primary or secondary success rate between patients with or without endoleak. Actuarial survival of all patients undergoing endovascular aneurysm repair was 96% at 1 year and was independent of endoleak status. Primary outcome success was 92% at 12 months and 88% at 18 months. Secondary outcome success was 96% at 12 months and 94% at 18 months. CONCLUSIONS: The presence or absence of endoleak on CT scan before hospital discharge does not appear to predict patient survival or aneurysm rupture rate after endovascular aneurysm repair using the AneuRx stent graft. Although the identification of blood flow in the aneurysm sac after endovascular repair is a meaningful finding and may at times indicate inadequate stent graft fixation, the usefulness of endoleak as a primary indicator of procedural success or failure is unclear. Therefore, all patients who have undergone endovascular aneurysm repair should be carefully followed up regardless of endoleak status.

Aortic Aneurysm, Abdominal↗
PubMed2000

Traumatic subcutaneous translocation of the spleen in an Old English sheepdog.

A 14-month-old entire male Old English sheepdog was presented with a slowly enlarging subcutaneous soft tissue swelling caudal to the last rib. Radiographic and ultrasonographic Investigations demonstrated a soft tissue mass closely adherent to the body wall, with a coarse hypoechoic pattern. Surgical exploration revealed a mass with the gross appearance of splenic tissue. The mass was adhered to a healed paracostal abdominal tear. Histological examination confirmed the resected tissue to be normal spleen.

Abdominal Injuries↗
PubMed2000

The gene encoding TBC1D1 with homology to the tre-2/USP6 oncogene, BUB2, and cdc16 maps to mouse chromosome 5 and human chromosome 4.

TBC1D1 is the founding member of a family of related proteins with homology to tre-2/UPS6, BUB2, and cdc16 and containing the tbc box motif of 180-220 amino acids. This protein family is thought to have a role in differentiation and in regulating cell growth. We set out to map the TBC1D1 gene in mouse and human. Segregation analysis of a TBC1D1 RFLP in two independent mouse RI (recombinant inbred) lines reveals that mouse Tbc1d1 is closely linked to Pgm1 on chromosome 5. The human TBC1D1 gene was assigned to human chromosome 4p15.1-->4q21 using Southern blot analyses of genomic DNAs from rodent-human somatic cell lines. A human-specific genomic fragment was observed in the somatic cell lines containing human chromosome 4 or the 4p15.1-->4q21 region of the chromosome. TBC1D1 maps to the region containing the ortholog of mouse Pgm1 adding another locus to this long region of conserved synteny between mouse and man.

Animals↗
PubMed2000

Abdominal aortic aneurysm rupture following endoluminal graft deployment: report of a predictable event.

PURPOSE: To describe the predictability of an abdominal aortic aneurysm (AAA) rupture secondary to a type II endoleak following stent-graft exclusion. METHODS AND RESULTS: An 81-year-old man with an enlarging AAA underwent endovascular repair using an AneuRx aortic stent-graft, but a type II endoleak fed by an accessory renal artery was detected at postprocedural computed tomography (CT). Surveillance CT scans at 6 and 16 months showed an increase in the aneurysm diameter and endoleak volume, but the patient refused advised treatment to close the leak. He suffered a fatal aneurysm rupture 24 months after endografting. Retrospective analysis of CT data documented progressive aneurysm enlargement that correctly predicted the rupture. CONCLUSIONS: Type II endoleaks can lead to aneurysm rupture. Three-dimensional (3D) spiral CT angiography offers an opportunity to track endoleak volume and the effect of exposure to systemic pressure on the aneurysm sac.

Aged↗
PubMed2000

Three novel paralogs of the rodent prolactin gene family.

The prolactin (PRL) family consists of a collection of genes expressed in the uterus, placenta and anterior pituitary. These cytokines/hormones participate in the control of maternal-fetal adaptations to pregnancy. In this report, we establish the presence of three new members of the PRL family. Novel expressed sequence tags (ESTs) with homology to PRL were isolated from embryonic and placental cDNA libraries. The cDNAs were sequenced and compared with those of other members of the PRL family. The three new cDNAs were assigned to the PRL family on the basis of sequence similarities and were referred to as PRL-like protein-J (PLP-J), PRL-like protein-K (PLP-K) and PRL-like protein-M (PLP-M). Both rat and mouse PLP-J cDNAs were identified. Rat PLP-J cDNA encodes for a predicted 211 amino acid protein containing a 29 amino acid signal peptide and two putative N-linked glycosylation sites, whereas the mouse PLP-J cDNA encodes for a 212 amino acid protein containing a 29 amino acid signal peptide with a single N-linked glycosylation site. Rat and mouse PLP-J proteins share approximately 79% and 70% nucleotide and amino acid sequence identity, respectively. A full-length rat PLP-K cDNA and a partial tentative mouse PLP-K cDNA were identified. The rat PLP-K cDNA encodes for a predicted 228 amino acid protein containing a 31 amino acid signal peptide and one putative N-linked glycosylation site; the mouse PLP-M cDNA encodes for a predicted 228 amino acid protein containing a 28 amino acid signal peptide and one putative N-linked glycosylation site. Genes for PLP-J, PLP-K and PLP-M are situated at the Prl family locus on mouse chromosome 13. PLP-J was exclusively expressed in decidual tissue from both the mouse and rat. PLP-K was expressed in trophoblast cells of the chorioallantoic placenta and showed an apparent species difference. In the mouse, virtually all trophoblast lineages expressed PLP-K, whereas in the rat, PLP-K expression was restricted to the labyrinthine trophoblast cells. Mouse PLP-M expression was restricted to the junctional zone of the chorioallantoic placenta. In summary, we have identified three new members of the rodent PRL gene family that are expressed in uterine and placental structures. Future experimentation is needed to determine the specific roles of each of these ligands in the biology of pregnancy.

Amino Acid Sequence↗