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Biomedical subjects

P Shaw

Publications and source records attributed to P Shaw.

At least 73 records · Page 4Linked to original sources
PubMed1999

Frequent methylation silencing of p15(INK4b) (MTS2) and p16(INK4a) (MTS1) in B-cell and T-cell lymphomas.

The methylation status of p15(INK4b) (MTS2), p16(INK4a) (MTS1) and p14(ARF) (p16beta) was analyzed in 56 lymphomas by restriction-enzyme related polymerase chain reaction (PCR) (REP), methylation-specific PCR (MSP), and bisulfite genomic sequencing (BGS). Methylation of the p15 and p16 genes was detected, respectively, in 64% and 32% of the B-cell lymphomas, in 44% and 22% of the T-cell lymphomas, and in none of the 5 reactive lymph nodes analyzed. Both p15 and p16 genes were methylated more often in the high-grade (78% and 50%, respectively) than in the low-grade B-cell lymphomas (55% and 21%, respectively). For 5 cases, mapping of the methylated CpGs of the p16 promoter region confirmed the results of REP and MSP. In addition, a large variation in the methylation patterns of p16 exon 1 was observed, not only from one lymphoma to another, but also within a given tumor. Methylation of p15 and p16 was associated with an absence of gene expression, as assessed by reverse transcription-PCR. The p14 gene was unmethylated and normally expressed in all 56 tumors. We found no mutations of p15, p16, or p14 in any of the 56 lymphomas. Our results suggest a role for p15 and p16 gene methylation during lymphomagenesis and a possible association between p15 and p16 inactivation and aggressive transformation in B-cell and T-cell lymphomas.

Carrier Proteins↗
PubMed1999

The allogeneic response to cultured human skin equivalent in the hu-PBL-SCID mouse model of skin rejection.

BACKGROUND: Engineered tissues have been proposed for the treatment of a variety of conditions including the partial or complete replacement of human organs. To determine the basis for the rejection of these tissues, we analyzed the immune response to allogeneic human skin equivalent (HSE, also called Apligraf) in the humanized SCID mouse (hu-PBL-SCID). METHODS: Two models of hu-PBL-SCID were used for these studies. In one model, human skin or HSE was transplanted onto humanized mice so that graft survival could be analyzed. In the other model, skin grafts were allowed to heal on naive mice before humanization. This model was used to analyze the immunologic response to the vascularized skin allograft. Humanization was performed by adoptive transfer of human PBL into SCID mice by i.p. injection. RESULTS: Both human foreskin and HSE successfully engrafted onto naive SCID mice and remained stable for more than 6 months. In contrast, human foreskin was rejected by 21 days posttransplant in hu-PBL-SCID, whereas HSE consistently engrafted for more than 28 days. Treatment of HSE grafts with interferon-y for 5 days to induce maximal MHC class II molecule expression before grafting failed to induce rejection. HSE also engrafted onto hu-PBL-SCID mice that were exposed to alloantigen by prior injection with interferon-gamma-treated keratinocytes identical to those used to generate the HSE. In addition, we determined that humanization of SCID mice following engraftment and vascularization of human foreskin resulted in marked CD3+ T cell infiltrates and a lymphocyte-induced vasculitis. In contrast, the response in vascularized HSE was associated with minimal CD3+ T cell infiltration in the absence of vasculitis or morphological features of rejection. CONCLUSION: These results support the use of HSE and other allogeneic engineered tissues in humans provided that such tissues are limited in their antigen presenting capabilities. In addition, our findings suggest a critical function for the donor endothelial cell in rejection.

Animals↗
PubMed1999

Genomic organization, fine-mapping, and expression of the human islet-brain 1 (IB1)/c-Jun-amino-terminal kinase interacting protein-1 (JIP-1) gene.

Islet-brain 1 (IB1), a regulator of the pancreatic beta-cell function in the rat, is homologous to JIP-1, a murine inhibitor of c-Jun amino-terminal kinase (JNK). Whether IB1 and JIP-1 are present in humans was not known. We report the sequence of the 2133-bp human IB1 cDNA, the expression, structure, and fine-mapping of the human IB1 gene, and the characterization of an IB1 pseudogene. Human IB1 is 94% identical to rat IB1. The tissue-specific expression of IB1 in human is similar to that observed in rodent. The IB1 gene contains 12 exons and maps to chromosome 11 (11p11.2-p12), a region that is deleted in DEFECT-11 syndrome. Apart from an IB1 pseudogene on chromosome 17 (17q21), no additional IB1-related gene was found in the human genome. Our data indicate that the sequence and expression pattern of IB1 are highly conserved between rodent and human and provide the necessary tools to investigate whether IB1 is involved in human diseases.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Prognostic factors for relapse and pelvic lymph node metastases in early stage I adenocarcinoma of the cervix.

OBJECTIVES: The aim of this study was to assess the prognostic significance of local tumor factors in predicting lymph node metastases and/or recurrence in early adenocarcinoma of the cervix. METHODS: Patients were selected from the prospective computerized cervical cancer database of the division of gynecologic oncology. All patients had radical surgery and pelvic lymph node dissection. The study population consisted of all patients with stage I adenocarcinoma having tumor thickness <10 mm. Pathology was re-reviewed to assess histological subtype, depth, volume, grade, and presence of capillary lymphatic space involvement. RESULTS: The study group consisted of 68 patients, with a mean age of 40 years. The median follow-up was 40 months (range 8-102 months). The median tumor depth and volume were 2.8 mm (range 0.3-8.0 mm) and 237 mm(3) (range 0.1-7996 mm(3)), respectively. Twenty-two patients had tumor volumes greater than 600 mm(3), and of these, 5 (23%) patients either had positive pelvic lymph nodes (2) or developed recurrent disease (3) (none node positive) at a median time of 49 months. In comparison, 46 patients (68%) had tumor volumes of less than 600 mm(3), none of whom had positive pelvic lymph nodes or developed recurrence (P<0.005). Only 1 of 20 patients with a depth of invasion <2 mm had a tumor volume >600 mm(3) in comparison to 21 of 48 patients with deeper invasion (P<0.002). CONCLUSION: The incidence of positive pelvic lymph nodes and/or recurrence in this patient population is very low. As all patients with metastatic disease or recurrence had tumor volumes >600 mm(3), volume of disease rather than depth of invasion may be the single most important prognostic factor for the above events. However, many more patients will have to be studied to confirm this.

Adenocarcinoma↗
PubMed1999

Molecular authentication of Panax species.

Using conserved plant sequences as primers, the DNA sequences in the ribosomal ITS1-5.8S-ITS2 region have been amplified and determined for six Panax species, P. ginseng C. A. Mey. (Oriental ginseng), P. quinquefolius L. (American ginseng), P. notoginseng (Burkill) F. H. Chen (Sanchi), P. japonicus C. A. Mey. (Japanese ginseng), P. trifolius L. and P. major Ting, as well as two common adulterants of ginseng, Mirabilis jalapa L. and Phytolacca acinosa Roxb. An authentication procedure based upon the restriction fragment length polymorphism (RFLP) in the region is able to differentiate between P. ginseng and P. quinquefolius, and to discriminate the ginsengs from the two common poisonous adulterants. Broader application of this approach to authenticate other morphologically similar Chinese medicinal materials is rationalised.

Base Sequence↗
PubMed1999

Ganciclovir-induced encephalopathy in a bone marrow transplant recipient.

Ganciclovir is widely used as prophylactic and pre-emptive therapy, as well as treatment, for CMV infection following BMT. We report a case treated with ganciclovir 5 days a week. Following escalation of the ganciclovir dose to a twice daily dose to treat CMV antigenaemia, he developed encephalopathy. His encephalopathy resolved with withdrawal of ganciclovir. Ganciclovir encephalopathy has been described in other groups of patients but has not been reported following BMT to date. With its widespread use this complication is likely to be seen more often.

Antilymphocyte Serum↗
PubMed1999

An unusual case of intrapulmonary granulocytic sarcoma presenting as interstitial pneumonitis following allogeneic bone marrow transplantation for acute myeloid leukaemia and responding to donor lymphocyte infusion.

We report a 45-year-old female with AML who underwent a T cell-depleted sibling allograft and relapsed a year later with extramedullary disease involving the lung parenchyma and presenting with the clinical and radiological features of interstitial pneumonitis. The patient was treated with donor lymphocyte infusion (DLI) resulting in complete resolution of the radiological signs. The unusual presentation and the management options are discussed.

Bone Marrow Transplantation↗
PubMed1999

Homologous chromosome pairing in wheat.

Bread wheat is a hexaploid (AABBDD, 2n=6x=42) containing three related ancestral genomes, each having 7 chromosomes, giving 42 chromosomes in diploid cells. During meiosis true homologues are correctly associated in wild-type wheat, but a degree of association of related chromosomes (homoeologues) occurs in a mutant (ph1b). We show that the centromeres are associated in non-homologous pairs in all floral tissues studied, both in wild-type wheat and the ph1b mutant. The non-homologous centromere associations then become homologous premeiotically in wild-type wheat in both meiocytes and the tapetal cells, but not in the mutant. In wild-type wheat, the homologues are colocalised along their length at this stage, but the telomeres remain distinct. A single telomere cluster (bouquet) is formed in the meiocytes only by the onset of leptotene. The sub-telomeric regions of the homologues associate as the telomere cluster forms. The homologous associations at the telomeres and centromeres are maintained through meiotic prophase, although, during leptotene, the two homologues and also the sister chromatids within each homologue are separate along the rest of their length. As meiosis progresses, first the sister chromatids and then the homologues associate intimately. In wild-type wheat, first the centromere grouping, then the bouquet disperse by the end of zygotene.

Meiosis↗
PubMed1999

Varicella vaccine in non-immune household contacts of children with cancer or leukaemia.

OBJECTIVE: To assess the immunogenicity and reactogenicity of a new formulation of live attenuated varicella vaccine (Oka strain) in non-immune household contacts of children with cancer or leukaemia. METHODOLOGY: This was an open study with one group. Healthy varicella-susceptible adults and children living in the same household as children with cancer or leukaemia were vaccinated with a new live attenuated varicella vaccine (Oka strain) which is stable when stored at 2-8 degrees C (refrigerator temperature) for at least 24 months (Varilrix). Children less than 13 years of age received one dose (0.5 mL containing at least 103.3 plaque forming units) by subcutaneous injection and those aged over 13 years received two doses 8 weeks apart. Adverse reactions following vaccination were recorded daily by the vaccinees. Post-vaccination antibody estimation was determined using indirect immunofluorescence 6 weeks after vaccination. RESULTS: Thirty-five seronegative subjects (28 children and 7 adults and adolescents) were vaccinated. All subjects tested (34) had seroconverted after vaccination. Local injection site reactions were experienced by 15/35. Other adverse reactions were uncommon (rash 2/35, fever (>/= 37.5 degrees C) 3/35). No cases of clinical varicella occurred amongst the high-risk household contacts of the vaccine. CONCLUSION: This is the first study of this formulation of varicella vaccine in household contacts of children with cancer or leukaemia. The vaccine was found to be safe and immunogenic, but further follow-up is needed to document duration of immunity.

Adolescent↗
PubMed1998

Colon cancer cell vaccine prepared with replication-deficient vaccinia viruses encoding B7.1 and interleukin-2 induce antitumor response in syngeneic mice.

A replication-deficient recombinant vaccinia virus, NYVAC, was developed by deleting 18 open reading frames in the vaccinia virus genome. Recombinant NYVAC, encoding the murine T cell co-stimulatory gene B7.1 (CD 80) (NYVAC-B7.1) and the murine interleukin-2 gene (NYVAC-IL-2), were prepared and the expression of B7.1 and the secretion of IL-2 were respectively confirmed in vitro. The use of these viruses to prepare a potent tumor cell vaccine was studied in a syngeneic murine CC-36 colon adenocarcinoma model. Mice were immunized on days 1 and 8 with 10(6) irradiated CC-36 cells that were infected with 10(7) plaque-forming units of either NYVAC-B7.1, NYVAC-IL-2 or a control virus, NYVAC-HR, which encodes a vaccinia virus host-range gene. These mice were then challenged with 10(8) viable CC-36 tumor cells on day 15. All mice (10/10) in a group that had received no vaccination and all mice (20/20) in a group that had received a control vaccine of CC-36/NYVAC-HR developed tumor 4-weeks after tumor cell challenge. Interestingly, only 16/20 mice in a group that had received CC-36/ NYVAC-B7.1 showed the development of tumor after the same interval. The protection against tumor development and the reduction in tumor burden (as mean tumor diameter, 4 weeks after tumor challenge) were significant in this group when compared to groups that were either unvaccinated or vaccinated with CC-36/NYVAC-HR (mean tumor diameter = 6.51+/-3.2 mm compared to 26.5+/-0.9 mm or 26.2+/-1.8 mm respectively) (P = < 0.05). The protection against tumor in a group of mice that received CC-36/ NYVAC-IL-2 vaccination was similar to that in the unvaccinated group or the group receiving a CC-36/NYVAC-HR control vaccination. However, in a survival experiment, mice that received either CC36/NYVAC-B7.1 or CC-36/ NYVAC-IL-2 vaccination on the day of tumor transplantation survived significantly longer than mice that had not been vaccinated (median survival 60+ days, 60+ days or 23.5 days respectively) (P = < 0.05). Interestingly, when a therapeutic tumor vaccination was performed on day 4 after tumor transplantation, mice that had been vaccinated with either CC36/NYVAC-B7.1 or CC-36/NYVAC-IL-2 did not show an improved survival when compared to mice in the control that had not been vaccinated (median survival 28 days compared to 26 days or 25 days respectively). However, mice that had received a therapeutic vaccination with CC-36 cells infected with both NYVAC-B7.1 and NYVAC-IL-2, 4 days after tumor transplantation, survived significantly longer than control mice that had not received any vaccination (median survival 29.5 days compared to 25 days respectively) (P<0.05). These results suggest that a replication-deficient recombinant NYVAC encoding the B7.1 gene and NYVAC encoding the IL-2 gene can be used to produce an effective vaccinia-virus-augmented tumor cell vaccine.

Adenocarcinoma↗
PubMed1998

The use of computer-generated three-dimensional models in orbital reconstruction.

In this paper we describe the application of three-dimensional (3D) imaging and computer-generated models in the management of orbital deformity. The technique was found to be particularly useful in posttraumatic deformity and fibrous dysplasia involving the orbit. Further application was found in cases of radiation hypoplasia, high facial cleft, and facial atrophy. Funding restrictions necessitate appropriate selection of cases when using new and expensive 3D imaging rather than traditional and less expensive methods. To remain within a realistic budget only those patients who will clearly benefit from the third dimension compared with traditional methods of assessment and management should be selected. These include patients requiring precise reduction or secondary reconstruction in which there is a matched normal anatomical component for comparison. This application is also only beneficial where the planned reconstruction is dimensionally stable.

Adolescent↗
PubMed1998

Meiosis: vive la difference!

The application of molecular and modern cell biological techniques is beginning to show that the classical picture of the meiotic process is an oversimplification. The comparison of different species and analysis of mutants have recently demonstrated that many of the features previously thought to be an integral part of meiosis can be altered in their timing or even entirely dispensed with. In plants, differences in the meiotic pathway have been observed, by using methods for 3-D optical imaging, between the polyploids maize and wheat. The fact that two such closely related species differ may be the result of different mechanisms for dealing with polyploidy or may be species differences, but shows that a detailed understanding of the process in the particular species of interest is necessary.

Animals↗
PubMed1998

Telekid Care: bringing health care into schools.

BACKGROUND: Telekid Care is a project that attempts to overcome the health and educational barriers faced by children in urban Kansas City, Kansas. Telemedicine units were placed in school nurses' offices and linked to physicians at the University of Kansas Medical Center (KUMC). This paper describes the development of this project, presents utilization data, and discuss the lessons learned from the application of telemedicine in a school setting. RESULTS: Project developers spent 11 months designing the protocol and procedures for a pilot test. Four elementary schools participated, and 187 consultations were conducted. The most common reason for consultation was ear, nose, and throat (ENT) problems, making up 28% of all consults. Mandatory school physical examinations and dermatology problems combined to make up an additional 40% of the consults. The average time that elapsed between the request for a consult and confirmation of an appointment was 23 minutes. When immediate service was requested, 85% of the consults occurred the day of the request. These results strongly demonstrate telemedicine's ability to offer immediate service to children in need. CONCLUSION: Telemedicine enabled underserved inner-city children to gain access to health services. This service was most effective when it was integrated into the delivery system. Furthermore, community groups strongly favored the project, positively influencing its acceptance as an innovative health care delivery system.

Appointments and Schedules↗
PubMed1998

Long-term survival after locally aggressive anorectal melanoma.

Anorectal melanoma is a rare disease and, unlike cutaneous melanoma, there are few guidelines regarding optimal management. It has a reputation for having a poor prognosis, which has been attributed to a delay in diagnosis and to a lack of effective systemic therapy. It has also been suggested that the biology of this tumor may differ from that of cutaneous melanoma. An interesting case of anorectal melanoma is presented which highlights the unique considerations and challenges encountered by medical oncologists and surgeons who treat this disease.

Aged↗
PubMed1998

A randomised trial of the durability of non-allergenic latex-free surgical gloves versus latex gloves.

A prospective randomised trial was performed to compare the robustness of a new non-latex surgical glove with a standard latex glove when worn by four general surgeons in a district general hospital. Gloves were retrieved after surgery and examined using the European Standard Test for punctures. The overall puncture rate was 10.1%, and there was no significant difference in the rates between the two types of glove, although punctures in the non-latex glove tended to be larger and more readily noted by the wearer. The increase in latex allergy among health care staff dictates the need for gloves made from other materials, which may also be useful for operations on latex-allergic patients.

Attitude of Health Personnel↗
PubMed1997

Association of homologous chromosomes during floral development.

Reduction in chromosome number and genetic recombination during meiosis require the prior association of homologous chromosomes, and this has been assumed to be a central event in meiosis. Various studies have suggested, however, that while the reduction division of meiosis is a universally conserved process, the pre-meiotic association of homologues differs among organisms. In the fruit fly Drosophila melanogaster, some somatic tissues also show association of homologues [1,2]. In the budding yeast Saccharomyces cerevisiae, there is some evidence for homologue association during the interphase before meiotic division [3,4], and it has been argued that such associations lead directly to meiotic homologue pairing during prophase I [5]. The available evidence for mammals suggests that homologous chromosomes do not associate in germ cells prior to meiotic prophase [6]. To study the occurrence of homologue pairing in wheat, we have used vibratome tissue sections of wheat florets to determine the location of homologous chromosomes, centromeres and telomeres in different cell types of developing anthers. Fluorescence in situ hybridization followed by confocal microscopy demonstrated that homologous chromosomes associate pre-meiotically in meiocytes (germ-line cells). Surprisingly, association of homologues was observed simultaneously in all the surrounding somatic tapetum cells. Homologues failed to associate at equivalent stages in a homologue recognition mutant. These results demonstrate that the factors responsible for the recognition and association of homologues in wheat act before the onset of meiotic prophase. The observation of homologue association in somatic tapetum cells demonstrates that this process and meiotic division are separable.

Cell Nucleus↗