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Biomedical subjects

R A Robinson

Publications and source records attributed to R A Robinson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Phase II study of topotecan in patients with advanced non-small-cell lung cancer previously untreated with chemotherapy.

PURPOSE: This study was designed to assess the anti-tumor activity of topotecan (TPT) in patients with advanced non-small-cell lung cancer (NSCLC) previously untreated with chemotherapy. PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC with measurable disease in nonradiated fields were eligible. Other eligibility criteria were Zubrod performance status (PS) < or = 2 and adequate renal and liver function. TPT was administered at a dose of 1.5 mg/m2/d for 5 days over 30 minutes every 21 days. Of 48 registered patients, 40 were fully assessable. Nineteen patients had adenocarcinoma (AD), 14 squamous carcinoma (SCC), and seven poorly differentiated carcinoma. RESULTS: Six patients (15%) achieved a partial remission (PR) (durations: 8, 14, 18, 28, 56, and 61 weeks) and four patients a minor response; 10 patients had stable disease and 20 patients progressive disease. The PR rate was 36% (five of 14 patients) in patients with SCC versus 4% (one of 26 patients) in those with other histologies (P = .014). The overall median survival time was 38 weeks and 30% of patients were alive at 1 year. Grade 3 to 4 granulocytopenia and thrombocytopenia occurred after 76% and 10% of courses administered, respectively. No grade 3 to 4 nonhematologic toxicities were observed. Grade 1 or 2 nonhematologic toxicities consisted of nausea (46% and 5%), vomiting (31% and 7%), and fatigue (53% and 16%). CONCLUSION: TPT at the dose and schedule used has moderate antitumor activity in NSCLC; its activity is mostly limited to patients with SCC. TPT is well tolerated, with myelosuppression of short duration being the most common and limiting toxicity.

Adenocarcinoma↗
PubMed1996

p53 expression in placentas with hydropic change and hydatidiform moles.

Hydatidiform moles result from abnormal fertilization and have been divided into partial and complete forms based on morphologic, cytogenetic, and clinical features. Little is known about their pathogenesis or malignant transformation. We applied an immunohistochemical marker for the p53 tumor suppressor gene product to placentas with hydropic change and hydatidiform moles to determine whether abnormal p53 gene product accumulation occurs in molar gestations. Ploidy of these placentas was determined by flow cytometry and fluorescence in situ hybridization. The mean percentages of p53-positive cells was determined by counting 200 cytotrophoblastic and proliferating trophoblastic cells. The staining intensity was graded on a scale of 1+ (faint) to 3+ (strong). The mean percentage of p53-positive cells for the placentas were as follows: 8.9% +/- 10.5 for hydropic change; 28.0% +/- 13.2 for partial mole; and 41.0% +/- 19.6 for complete mole. There was a significant difference in p53 expression between hydropic change and partial mole (P = 0.05) and hydropic change and complete mole (P = 0.0008). Although there was a difference between partial mole and complete mole, this did not reach statistical significance (P = 0.15). Hydatidiform moles exhibited 2+ to 3+ staining intensity, whereas hydropic placentas exhibited weaker intensity (1-2+). The finding of p53 gene product overaccumulation in partial and complete moles suggests that p53 gene mutations or alternatively, post-transcriptional changes in the p53 gene product occur resulting in inactivation and stabilization of the protein. This may play a role in uncontrolled trophoblastic proliferation and neoplastic transformation.

Female↗
PubMed1996

Chromosome-specific aneusomy in carcinoma of the breast.

Fluorescence in situ hybridization was performed on touch preparations from 55 primary infiltrating ductal carcinomas of the breast to determine numeric chromosome abnormalities. The frequency of aneusomy, measured by both nondisomy and chromosomal gain, was determined for chromosomes X, 4, 6-12, 17, and 18 with the use of chromosome-specific, alpha-satellite DNA probes. The presence of chromosome-specific numeric abnormalities was correlated with established clinicopathological parameters, including tumor size, lymph node involvement, tumor grade, estrogen receptor level, and menopause status. In addition, a case-control study was performed to explore a possible association between chromosome-specific aneusomy and recurrence in lymph-node-negative patients. Although chromosomes 8 and 6 were most frequently aneusomic, numeric abnormalities of chromosomes 4 and 11 were most strongly associated with established prognostic factors. For chromosomes 4 and 11, strong associations were found with tumor involvement of lymph nodes and increased tumor size, along with a weaker association with tumor grade. In addition, numeric abnormalities of the following chromosomes were associated with the corresponding prognostic factors: chromosomes X, 7, and 12 with lymph node status; chromosomes 10, 17, and 6 with tumor size; and chromosomes 7, 12, 17, and X with tumor grade. No correlations were observed with estrogen receptor level or menopause status. In the case-control study performed on isolated nuclei of paraffin-embedded tissue from lymph node-negative breast cancer patients (19 cases and 19 controls), the gain of chromosome 4 was correlated with disease progression. These findings suggest that chromosome-specific aneusomy is associated with certain established prognostic factors and may be associated with disease progression.

Adult↗
PubMed1995

Glial hyaluronate-binding protein: a product of metalloproteinase digestion of versican?

Glial hyaluronate-binding protein (GHAP) is a 60 kDa glycoprotein with an amino acid sequence identical to that of the hyaluronate-binding region of versican, a large fibroblast aggregating proteoglycan found in the brain. Both GHAP and versican were identified by immunoblot in bovine brain extracts prepared only minutes after death. Human recombinant collagenase, stromelysin, mouse gelatinase and gelatinases isolated from human brain by affinity chromatography digest versican and give rise to a polypeptide with electrophoretic mobility identical to GHAP. Immunoblot analysis, peptide mapping and C-terminal amino acid sequencing indicate that the polypeptide generated by digestion with human brain gelatinases is identical to GHAP. We suggest that GHAP is a naturally occurring versican degradation product.

Amino Acid Sequence↗
PubMed1995

Some risk factors associated with clinical lameness in dairy herds in Minnesota and Wisconsin.

An observational study of the relationships between clinical lameness and herd-level risk factors was made in 18 dairy herds in Minnesota and Wisconsin. Lameness in the lactating cows was assessed by two observers during herd visits made in the summer of 1989 and the spring of 1990, using a uniform scoring system. A questionnaire was used to obtain information about the general management, routine hoof care, nutrition, housing and flooring on the farms. Factors associated with the prevalence of clinical lameness in the summer included stall moisture, the size of the exercise area for the lactating cows and the amounts of dry concentrates and fresh forages fed to them. Factors associated with clinical lameness in the spring included the use of parlour milking facilities and the frequency with which the rations for the lactating cows were balanced.

Animal Feed↗
PubMed1995

p53 protein overexpression in smooth muscle tumors of the uterus.

p53 is a nuclear phosphoprotein whose overexpression may portend a poor prognosis in a variety of neoplasms. In this immunohistochemical study we examined p53 overexpression in a variety of uterine smooth muscle tumors (34 leiomyosarcomas, 18 leiomyomas, and six smooth muscle tumors of uncertain malignant potential [STUMPs]). p53 immunoreactivity was observed in none of 18 (0%) leiomyomas, one of six (17%) STUMPs, and 16 of 34 (47%) leiomyosarcomas. Reactivity was not observed in the surrounding nonneoplastic uterine smooth muscle. Strong p53 overexpression in the leiomyosarcomas was significantly associated with high grade morphology (P = .013) and a high stage at the time of presentation (P = .021). In 25 leiomyosarcoma patients with clinical follow-up, p53 overexpression was associated with shorter length of survival (P = 0.024). However, this effect was not independent of tumor stage or grade. A regression analysis showed that tumor stage was the only independent predictor of length of survival. Our study size is small, and further studies are warranted to determine the significance and replicability of these findings.

Female↗
PubMed1995

Ploidy analysis by flow cytometry and fluorescence in situ hybridization in hydropic placentas and gestational trophoblastic disease.

Placentas with hydropic change may be hydropic degeneration (HD) or gestational trophoblastic disease (GTD), partial (PM) or complete (CM) hydatidiform mole. The separation of HD from PM and PM from CM by histological findings may be problematic in some cases and can be clarified with ploidy analysis. Fluorescence in situ hybridization (FISH) using a probe to chromosome 7 (D7Z1) was applied to tissue cut from paraffin blocks from 10 histologically representative cases each of HD, PM, and CM on which ploidy had been previously confirmed by flow cytometry from paraffin embedded tissue. Villous stromal cells and nonproliferative trophoblast were examined for number of signals/cell and percentage of cells/placenta with three hybridization signals. The mean number of hybridization signals/cell was HD 1.14; PM 1.79; and CM 1.17, with statistical significance between HD and PM (P < .0001), and PM and CM (P < .0001). The mean percentage of cells/placenta with three hybridization signals was HD 1.10%, PM 23.1%, and CM 2.11%, with statistical significance between HD and PM (P < .0001), and PM and CM (P < .0001). In addition, there was no overlap in the mean percentage of cells with three hybridization signals between HD and PM, and PM and CM. Chromosome 2 probe (D2Z1) was applied to tissues that had three chromosome 7 signals to exclude trisomy, and in all cases three signals were present confirming triploidy in PM. FISH can identify diploid and triploid hydropic placentas in paraffin-embedded tissue to assist in differentiating HD from PM, and PM from CM.

Chromosomes, Human, Pair 2↗
PubMed1995

Lymphomas of the oral soft tissues are not preferentially associated with latent or replicative Epstein-Barr virus.

OBJECTIVES: Epstein-Barr virus is periodically shed in the saliva of persons infected by the virus. Epstein-Barr virus has been implicated in the pathogenesis of certain subtypes of lymphoma, particularly high-grade lymphomas. Because high-grade subtypes represent the majority of lymphomas that arise in oral soft tissues, we hypothesized that Epstein-Barr virus might be preferentially associated with oral lymphomas. STUDY DESIGN: A series of 34 oral lymphomas were diagnosed according to the revised European-American classification scheme. They were examined for the presence of latent Epstein-Barr virus by EBER1 in situ hybridization and for expression of the Epstein-Barr virus replicative protein, BZLF1, by immunohistochemistry. RESULTS: Epstein-Barr virus EBER1 transcripts were detected in 11 of 31 oral lymphomas including 7 of 10 AIDS-related lymphomas and only 4 of 21 lymphomas that occurred in nonimmunocompromised persons. The Epstein-Barr virus-containing lymphomas were all high-grade histologic subtypes, that is, diffuse large cell, immunoblastic, or Burkitt's lymphomas. In contrast, Epstein-Barr virus was not detected in any of five low-grade oral lymphomas. In the single case of T-cell lymphoma in this study, EBER1 was expressed in the tumor cells. A switch from viral latency to replication, as measured by EBV BZLF1 expression, was identified in rare lymphoma cells in only four cases. This rate of viral replication was not higher than what has been reported in lymphomas arising at other anatomic sites. Although one of our lymphomas arose at a site of previous oral hairy leukoplakia, there was no other evidence that Epstein-Barr virus replication predisposed to development or persistence of oral lymphomas. CONCLUSIONS: These data suggest that even though Epstein-Barr virus is frequently found in oral secretions, neither latent nor replicative Epstein-Barr virus is present more commonly in oral lymphomas than in lymphomas arising in other anatomic sites, when controlling for immunodeficiency status.

Adolescent↗
PubMed1995

Medullary carcinoma of the thyroid metastatic to the temporal bone.

We report a case of proven thyroid medullary carcinoma, metastatic to the temporal bone. Review of the otolaryngology literature demonstrates that this is the first such report. The patient presented with symptoms, physical examination, and imaging studies suggestive of a glomus jugulare tumour. The pre-operative diagnosis of metastatic thyroid medullary carcinoma, however, was made, based on a history of medullary carcinoma of the thyroid with previous metastases as well as an elevation in calcitonin levels. Histological examination of the surgical specimen confirmed the diagnosis.

Carcinoma, Medullary↗
PubMed1995

Transient neurologic deficit after spinal anesthesia: local anesthetic maldistribution with pencil point needles?

Recent reports of transient neurologic deficits have raised concern about the potential toxicity of single-dose spinal 5% lidocaine in 7.5% dextrose. Two cases of volunteers who experienced minor local sensory deficits after slow (60 s) injections of 2 mL 5% lidocaine via Whitacre needles are described. One case was a result of a double injection because of a "failed" block. It seemed possible that the neurologic deficit in these cases resulted from neurotoxicity associated with maldistribution of local anesthetic. Using an in vitro spinal model, we investigated drug distribution resulting from injections through side-port spinal needles to determine whether the use of these needles could result in high local concentrations of hyperbaric solutions. A spinal canal model was fabricated using human magnetic resonance measurements. The model was placed in a surgical supine position and filled with lactated Ringer's solution to simulate the specific gravity of cerebral spinal fluid at 22 degrees C. A hyperbaric solution of phthalocyanine blue dye and dextrose (SG 1.042), simulating the anesthetic, was injected through three different needles (27-gauge 4 11/16-in. Whitacre, 25-gauge 3 1/2-in. Whitacre, 25-gauge 3 1/2-in. Quincke). Triplicate injections were done at rapid (2 mL/10 s) and slow (2 mL/60 s) rates, with needle side ports oriented in a sacral and cephalad direction. At slow rates of injection, using 27- or 25-gauge sacrally directed Whitacre needles, injections showed evidence of maldistribution with extrapolated peak sacral lidocaine concentrations reaching 2.0%. In contrast, distribution after slow injection through sacrally directed Quincke needles was uniform.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Serologic studies of experimentally induced Salmonella choleraesuis var kunzendorf infection in pigs.

Two indirect ELISA containing outer membrane protein (OMP) and lipopolysaccharide (LPS) antigens from a field isolate of Salmonella choleraesuis var kunzendorf were developed and evaluated in experimentally infected and uninfected control pigs. Experimentally induced infection with S choleraesuis was successfully established in 10 pigs by oral inoculation with 10(8) organisms, and 3 pigs died of clinical salmonellosis at postinoculation (PI) weeks 1, 2, and 4. Swab specimens from tonsils, nostrils, and rectum of pigs were obtained for culture, and sera were evaluated at weekly intervals for 9 weeks after inoculation. The ELISA containing OMP and LPS antigens with either anti-swine IgG or protein albumin-to-globulin ratio (antiglobulin) conjugates were standardized for serologic evaluation. All 4 ELISA (2 OMP and 2 LPS) detected seroconversion by PI week 3 and had sensitivities and specificities of 97.8 and 88.8, 100 and 100, 95.6 and 88.8, and 93.3 and 72.5%, at their ideal cutoff points (negative mean optical density +2 SD). There was excellent agreement between all 4 ELISA systems as determined by kappa values. Cultures of fecal, tonsil, and nasal swab specimens were positive for S choleraesuis until the fourth week of infection. Fecal swab specimens from 1 pig were positive for S choleraesuis until PI week 7. Persistent infection after antemortem culture results were negative was detected by all 4 ELISA, which indicated consistently high titers until the end of PI week 9.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

p53 immunoreactivity in primary and metastatic prostatic adenocarcinoma.

p53 is a tumor suppressor protein that is overexpressed in a variety of human neoplasms, including prostatic adenocarcinoma. Recent studies have demonstrated a significant positive correlation between extent of p53 overexpression and tumor grade in prostatic adenocarcinoma. Because it appears that mutations of p53 might play a role in the pathogenesis of a subset of biologically aggressive prostatic neoplasms, we sought to examine the frequency of p53 overexpression in primary and metastatic prostatic adenocarcinoma. Using a monoclonal antibody (D07) directed against both the wild-type and mutant forms of p53, we examined p53 immunoreactivity in 36 cases of primary prostatic adenocarcinoma, 17 cases of metastatic prostatic adenocarcinoma involving lymph nodes and 15 cases of metastatic prostatic adenocarcinoma involving bone. Twenty-eight percent (10/36) of the primary tumors displayed nuclear staining for p53. Increased p53 immunoreactivity was observed in only 6% (1/16) of prostatic adenocarcinomas with a total Gleason score of 6 or less, as compared with 45% (9/20) of those adenocarcinomas with a Gleason score of 7 or more. Fifty-nine percent (10/17) of the lymph node metastases and 43% (6/14) of the bone metastases displayed nuclear immunoreactivity for p53. Our results indicate that increased p53 expression is positively correlated with increased histologic grade and with the presence of metastatic disease in patients with prostatic adenocarcinoma, and they suggest that mutations of the p53 gene may play a role in mediating the behavior of a biologically aggressive subset of this common neoplasm.

Adenocarcinoma↗
PubMed1995

p53 expression in Bowen's disease and in microinvasive squamous cell carcinoma of the skin.

p53 is a tumor suppressor gene whose protein product is overexpressed in several human tumors. In this study we used a monoclonal antibody (DO7) direct against p53 and a previously described antigen retrieval methodology to examine p53 expression in 27 cases of microinvasive squamous cell carcinoma of the skin and in 10 cases of Bowen's disease. Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections that had been microwave-heated to improve antigenicity. Positive nuclear staining for p53 was observed in 23 of 27 (85%) cases of microinvasive squamous cell carcinoma and in five of 10 (50%) cases Bowen's disease. With the exception of occasional focal positive staining of basal layer cells, no p53 immunoreactivity was observed in normal skin. Our results demonstrate that increased expression of the p53 protein is a common finding in both in situ and microinvasive squamous cell carcinoma of the skin, and they suggest that loss of normal p53 tumor suppressor activity may be an important mechanism of oncogenesis in these neoplasms.

Bowen's Disease↗
PubMed1994

Active-site labeling of an aminoglycoside antibiotic phosphotransferase (APH(3')-IIIa).

The aminoglycoside antibiotics are inactivated by modifying enzymes that are now widely distributed in many pathogenic bacteria. This situation threatens the continued use of these clinically important drugs. We have undertaken studies to understand the molecular mechanism of aminoglycoside resistance, and we report the affinity labeling of the enterococcal aminoglycoside 3'-phosphotransferase, APH(3')-IIIa, with an electrophilic ATP analogue, 5'-[p-(fluorosulfonyl)benzoyl]adenosine (FSBA). Incubation of purified APH(3')-IIIa with FSBA resulted in time-dependent irreversible inactivation of enzyme activity with a binding constant, Ki, of 0.406 mM and a rate of maximal inactivation, kmax, of 0.086 min-1. Addition of ATP completely protected the enzyme from inactivation, consistent with labeling of the ATP binding site. Reaction of APH(3')-IIIa with [14C]FSBA showed that inactivated APH(3')-IIIa incorporates 1 mol of FSBA/mol of enzyme. Peptide mapping of FSBA-inactivated APH(3')-IIIa resulted in the identification of two peptide peaks with highly increased absorbance at 260 nm, indicative of covalent labeling with FSBA. Analysis by electrospray ionization mass spectrometry and Edman degradation revealed two tryptic peptides, Val31-Lys44 and Leu34-Arg49, which incorporated the FSBA label at Lys33 and Lys44, respectively. This establishes the importance of the N-terminal region of APHs in ATP binding, a region of these enzymes which has heretofore not been considered for involvement in substrate binding.

Adenosine↗
PubMed1994

Fine-needle detection of cytomegalovirus parotitis in a patient with acquired immunodeficiency syndrome.

Parotid enlargement is common in patients infected with human immunodeficiency virus type 1. We present a case of cytomegalovirus infection of the parotid gland in a patient with the acquired immunodeficiency syndrome. This case is notable because fine-needle aspiration provided the diagnosis. We therefore present a quick and inexpensive method of detecting a potentially fatal infection that has previously been unrecognized by the medical community.

AIDS-Related Opportunistic Infections↗
PubMed1994

DNA ploidy and P-glycoprotein expression as predictive factors of response to neoadjuvant chemotherapy for invasive bladder cancer.

OBJECTIVE: To identify a factor or factors that could predict response of muscle invasive transitional cell carcinoma of the bladder to neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy. METHODS: DNA ploidy analysis and immunohistochemical staining for p-glycoprotein (the product of the multidrug resistance gene, MDR-1) were performed on bladder biopsies obtained prior to chemotherapy. Radical cystectomy specimens were utilized for complete pathologic staging. RESULTS: Tissue was available for DNA ploidy analysis in 25 patients. Ten patients had complete responses to neoadjuvant chemotherapy and 15 patients did not respond. Nineteen patients had aneuploid tumors, of which 7 (37%) were complete responders. Six patients had diploid tumors, of which 3 (50%) were complete responders. This difference was not statistically significant. Tissue was available for immunostaining in 15 patients. Seven of 9 patients (78%) who did not respond to chemotherapy stained positively for p-glycoprotein, whereas 5 of 6 patients (83%) who had complete responses stained positively. This difference was not statistically significant. CONCLUSIONS: Neither DNA ploidy nor p-glycoprotein expression appears to predict successfully those patients likely to respond to neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy in the treatment of invasive bladder cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Self-peptides bound to the type I diabetes associated class II MHC molecules HLA-DQ1 and HLA-DQ8.

Genetic susceptibility to several autoimmune disorders is associated with the expression of certain MHC class II alleles. Insight into the etiology of such diseases awaits the identification of the class II restriction elements and the possible pathogenic peptides. Towards these aims, self-peptides bound to HLA-DQ1 and HLA-DQ8, allotypes considered to be neutral and permissive respectively towards the development of insulin-dependent diabetes mellitus, are reported. These naturally processed peptides were isolated from immunoaffinity purified HLA-DQ molecules expressed in cultured B lymphocytes. The chromatographic profiles of the peptide repertoires are unique, whereas the size distributions exhibit general similarity to those reported for naturally processed self-peptides bound to HLA-DR. Twenty-eight individual peptides representing 10 nested sets were identified by combined Edman microsequencing and mass spectrometry. Peptide length varied from 13 to 74 amino acids. Source proteins included MHC molecules and other integral membrane proteins, as well as secretory, cytosolic and mitochondrial proteins. Promiscuous invariant chain peptides were identified among the self-peptides bound to HLA-DQ8. No dominant amino acid markers suggestive of particular enzymatic processing events were detected. Some structural features of DQ1 and DQ8 that may relate to the bound peptides are discussed. Peptide specificity was confirmed in binding assays with purified HLA-DQ and HLA-DR protein.

Amino Acid Sequence↗