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Biomedical subjects

M Glenn

Publications and source records attributed to M Glenn.

At least 19 recordsLinked to original sources
PubMed2002

DNA vaccination against feline calicivirus infection using a plasmid encoding the mature capsid protein.

Feline calicivirus (FCV), a member of the diverse family Caliciviridae, is a respiratory and oral pathogen of cats. Although conventional FCV vaccines are available, there are some safety and efficacy problems associated with their use. The potential of DNA vaccination against FCV infection was therefore explored. Four cats were inoculated intramuscularly with three 100 microg doses, 2 weeks apart, with a plasmid (pF9VAC) containing the mature capsid protein gene of FCV strain F9. Four control cats received the same plasmid lacking the FCV gene insert. All eight cats showed clinical signs following heterologous challenge with FCV strain LS027. However, rectal temperatures and general clinical sign scores were significantly lower in vaccinates compared to controls, and there was a marked difference in ulcer distribution between the two groups. Although no serological responses were detected in either group prior to challenge, post-challenge titres in the vaccinated group were generally higher. The results indicate that partial protection against a calicivirus is possible by DNA vaccination but that other approaches to enhance efficacy such as the use of cytokine genes or prime-boost protocols may also be required.

Animals↗
PubMed2001

Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol.

Patient-tumor-specific oligonucleotides were generated for the detection of minimal residual disease (MRD) in a highly specific and sensitive clonotypic polymerase chain reaction (cPCR). The clone-specific region of highest diversity, CDR-III, was PCR amplified and sequenced. Nested CDR-III clonotypic primers were used in a semi-nested cPCR with a sensitivity of at least 1 in 10(5) cells. Patients with protocol-eligible Rai intermediate or high-risk chronic lymphocytic leukemia (CLL) received induction with fludarabine 25 mg/m(2) per day for 5 days every 4 weeks for 6 cycles, followed by consolidative high-dose cyclophosphamide (1.5, 2.25, or 3g/m(2)). cPCR was performed on peripheral blood and bone marrow mononuclear cells. All 5 patients achieving a clinical partial remission (PR) studied by cPCR were positive. Five patients achieved nodular PR (nPR) (residual nodules or suspicious lymphocytic infiltrates in a bone marrow biopsy as the sole suggestion of residual disease). Five of 5 patients with nPR were cPCR positive. In contrast, flow cytometry for CD5-CD19 dual staining and kappa--lambda clonal excess detected MRD in only 3 of the same 5 nPR patients, all of whom were cPCR positive, and immunohistochemistry detected MRD in only 1 of 4 assessable patients. Three of 7 CR patients evaluable by cPCR had MRD. Only 1 CR patient had MRD by flow cytometry; that patient was also cPCR positive. These data support the conclusions that nodular PR in CLL represents MRD and that clonotypic PCR detects MRD in CLL more frequently than flow cytometry or immunohistochemistry. (Blood. 2001;97:1929-1936)

Antigens, CD↗
PubMed2000

A novel gene STORP (STOmatin-Related Protein) is localized 2 kb upstream of the promyelocytic gene on chromosome 15q22.

We generated a 100-kb map of the region 5' of the PML (promyelocytic leukemia) gene on human chromosome 15q22 and identified a new gene provisionally named STORP for stomatin-related protein. The STORP gene is positioned 2 kb upstream of the PML gene in a head-to-head configuration, and contains 7 exons spanning a genomic region of about 11 kb. There is an open reading frame of 398 amino acids, which would encode a protein of 45 kD. Northern blot analysis demonstrated that the STORP gene has a ubiquitous pattern of expression similar to that of the PML gene. Hybridization of STORP cDNA probe to genomic DNA from other species demonstrated that the STORP gene is conserved among mammalian vertebrates and that the physical linkage with PML is conserved in mice. Unlike PML, the STORP gene is not induced by interferon alpha (IFNalpha), and thus can be distinctly regulated from the PML gene. STORP is homologous to the EPB72 gene coding for the erythrocyte band 7 integral membrane protein or stomatin, which is deficient in a certain form of hereditary stomatocytosis. The function of STORP is unknown. Further study will focus on studying its potential role in red cell function and disorders.

Amino Acid Sequence↗
PubMed2000

Consolidation therapy with high-dose cyclophosphamide improves the quality of response in patients with chronic lymphocytic leukemia treated with fludarabine as induction therapy.

Fludarabine is the most active agent in the treatment of chronic lymphocytic leukemia (CLL). Despite this activity only a minority of patients treated with fludarabine achieve a complete response. We evaluated a new treatment program of sequential therapy with fludarabine followed by high-dose cyclophosphamide in previously untreated patients with CLL. This report details the results in 25 patients with previously untreated CLL. Patients received fludarabine (25 mg/m2/day x 5 days every 4 weeks for six cycles) as induction followed by consolidation with high-dose cyclophosphamide at one of three dose levels 1.5 g/m2, 2.25 g/m2, or 3 g/m2 administered every 2 weeks for three doses. High-dose cyclophosphamide was given with G-CSF support (5 microg/kg/day days 3-12). Complete response (CR) required a normal physical examination, normal CBC, a normal bone marrow evaluation including no residual lymphoid nodules on biopsy. A nodular response was defined as a complete response with the exception of an occasional residual nodule seen on bone marrow biopsy. Flow cytometric analysis for CD5:CD19 dual staining and kappa/lambda clonal excess was performed in all patients as a sensitive measure of minimal residual disease (MRD). Selected patients had patient/tumor-specific oligonucleotides generated that were subsequently used in a polymerase chain reaction as an extremely sensitive measure of MRD. There were no treatment-related deaths and no patient encountered unacceptable toxicity. After completion of this sequential regimen 76% (95% confidence interval: 59-93%) of patients had a major response: eight (32%) achieved a CR, four (16%) a nodular response, seven (28%) a PR, and six patients (24%) failed. Four patients withdrew from study during induction with fludarabine and did not receive at least one cycle of cyclophosphamide. Of the 21 patients who received consolidation with cyclophosphamide 10 (48%) had an improved quality of response when compared to that achieved with fludarabine. Two patients (8%) had no disease detectable by flow cytometry ('flow cytometric' CR) after six cycles of fludarabine. This improved to nine patients (36%) after high-dose cyclophosphamide. Following consolidation with high-dose cyclophosphamide three patients (12%) tested negative by PCR. All of these patients had morphologic evidence of residual disease after six cycles of fludarabine. Consolidation with high-dose cyclophosphamide increased the fraction of patients achieving a nodular response or CR three-fold (16% to 48%). This appears to be clinically relevant because with a median follow-up of 52 (range 34-78) months the projected 6-year survival for patients achieving a CR or NR is 91% compared to 41% for all others (P = 0.012). We conclude that sequential therapy with fludarabine followed by high-dose cyclophosphamide in previously untreated patients with CLL is safe and can improve the quality of response in a large proportion of patients compared to therapy with fludarabine alone.

Adult↗
PubMed2000

Expression of the hydrogen peroxide-generating enzyme fatty acyl CoA oxidase activates NF-kappaB.

Peroxisome proliferators are a class of hepatic carcinogens in rodents and have been proposed to act in part by increasing oxidative stress. Fatty acyl CoA oxidase (FAO), which is highly induced by peroxisome proliferators, is the hydrogen peroxide-generating enzyme of the peroxisomal beta-oxidation pathway. We previously showed that the treatment of rats and mice with the peroxisome proliferator ciprofibrate resulted in increased hepatic NF-kappaB activity and suggested that this effect may be secondary to the action of H2O-generating enzymes. To test this possibility directly, we have determined whether transient overexpression of FAO, in the absence of peroxisome proliferators, leads to NF-kappaB activation. Here, we show that FAO overexpression in Cos-1 cells, in the presence of an H2O-generating substrate, can activate a NF-kappaB regulated reporter gene. Electrophoretic mobility shift assays further demonstrated that FAO expression increases nuclear NF-kappaB DNA binding activity in a dose-dependent manner. The antioxidants vitamin E and catalase can inhibit this activation. These results indicate that FAO mediates, at least in part, peroxisome proliferator-induced NF-kappaB activation.

Acyl-CoA Oxidase↗
PubMed1999

Nucleotide sequence of UK and Australian isolates of feline calicivirus (FCV) and phylogenetic analysis of FCVs.

We have determined the first complete genome sequence and capsid gene sequences of feline calicivirus (FCV) isolates from the UK and Australia. These were compared with other previously published sequences. The viruses used in the comparisons were isolated between 1957 and 1995 from various geographical locations and obtained from cats showing a range of clinical signs. Despite these diverse origins, comparisons between all strains showed a similar degree of sequence variation within both ORF1 (non-structural polyprotein) and ORF2 (major capsid protein) (amino acid distances of 7.7-13.0% and 8.8-18.6%, respectively). In contrast, ORF3 (putative minor structural protein) sequences indicated a more heterogenous distribution of FCV relatedness (amino acid distances of 1.9-17.9%). Phylogenetic analysis suggested that, unlike some other caliciviruses, FCV isolates within the current data set fall into one diverse genogroup. Within this group, there was an overall lack of geographic or temporal clustering which may be related to the epidemiology of FCV infection in cats. Analysis of regions of variability in the genome has shown that, as well as the previously identified variable regions in ORF2, similar domains exist within ORFs 1 and 3 also, although to a lesser extent. In ORF1, these variable domains largely fall between the putative non-structural protein functional domains.

Amino Acid Sequence↗
PubMed1999

Identification of a spliced gene from Kaposi's sarcoma-associated herpesvirus encoding a protein with similarities to latent membrane proteins 1 and 2A of Epstein-Barr virus.

Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) is a novel herpesvirus implicated as the causative agent of Kaposi's sarcoma (KS), primary effusion lymphoma, and some cases of multicentric Castleman's disease. KSHV persists in the majority of KS spindle (endothelial tumor) cells and lymphoid cells in a latent form, with only a limited set of viral genes expressed in a tissue-specific manner. Here, we report the identification of a family of alternatively-spliced transcripts of approximately 7.5 kb expressed in latently infected body cavity-based lymphoma (BCBL) cell lines which are predicted to encode membrane proteins with similarities to the LMP2A and LMP1 proteins of Epstein-Barr virus. In two highly divergent sequence variants of the right end of the KSHV genome, alternative splicing of eight exons located between KSHV ORF 75 and the terminal repeats yields transcripts appropriate for proteins with up to 12 transmembrane domains, followed by a hydrophilic C-terminal, presumably cytoplasmic, domain. This C-terminal domain contains several YxxI/L motifs reminiscent of LMP2A and a putative TRAF binding site as in LMP1. In latently (persistently) infected BCBL cells the predominant transcript utilizes all eight exons, whereas in phorbol-ester-induced cells, a shorter transcript, lacking exons 4 and 5, is also abundant. We also found evidence for an alternative use of exon 1. Transfection of an epitope-tagged cDNA construct containing all exons indicates that the encoded protein is localized on cell surface and intracellular membranes, and glutathione S-transferase pull-down experiments indicate that its cytoplasmic domain, like that of LMP1, interacts with TRAF1, -2, and -3. Two of 20 KS patients had antibodies to the hydrophilic C-terminal domain, suggesting that the protein is expressed in vivo.

Alternative Splicing↗
PubMed1996

Young adult exercisers and nonexercisers differ in food attitudes, perceived dietary changes, and food choices.

Health experts recommend merging a healthy diet and adequate physical activity into one behavior. This study compared attitudes about foods, recent dietary changes, and food choices of 319 18- to 24-year-olds, who defined themselves as exercisers or nonexercisers. Subjects were recruited by telephone and were mailed questionnaires that asked about factors influencing food selection and changes in intake of high-fat foods. Exercisers considered it more important to eat nutritious foods; ate more nutrient-dense, low-fat foods; and more frequently met the Food Guide Pyramid recommended grain and fruit intakes than nonexercisers. Female exercisers more often perceived foods high in calcium to be fattening and not healthful, and they reported decreasing their intake of high-fat foods more than did female nonexercisers. Some merging of healthy diet and exercise behavior is evident among the young adult exercisers in this study. Nutrition and exercise messages targeted to young women should emphasize low-calorie calcium sources.

Adolescent↗
PubMed1988

Wound tension in rhytidectomy. A preliminary report.

In superficial musculoaponeurotic system (SMAs) suspension procedures in rhytidectomy, skin closing tension seems to be lower at the main anchor points than with non-SMAS procedures. To evaluate this clinical impression, a preliminary investigation into the effect of SMAS suspension on wound closing tension was undertaken. Intraoperatively, skin closing tension was compared with and without SMAS plication sutures at the two key anterior and posterior skin anchor points. Results confirmed decreased tension with SMAS plication. Anteriorly in the temporal part of the scalp, a significant difference of 87 g was demonstrated. Posteriorly in the occipital hairline, a significant difference of 96 g was demonstrated. Individual differences in tension were more pronounced in patients with prominent SMAS laxity than in those patients with mild laxity.

Aged↗
PubMed1987

Lack of effect of dopamine receptor blockade on the TSH response to TRH in borderline personality disorder.

We recently reported that some patients with borderline personality disorder (BPD) exhibit a blunted thyrotropin (thyroid-stimulating hormone; TSH) response to thyrotropin-releasing hormone (TRH). Because it is known that dopamine can inhibit the TSH response to TRH and that some patients with BPD show improvement with antipsychotic (dopamine-blocking) medication, we investigated whether haloperidol could reverse the blunted TSH response in BPD. Of 12 patients with BPD, three showed a blunted TSH response that did not normalize with haloperidol. Furthermore, there were no overall group changes in TSH response with haloperidol. The present study suggests that reductions in TSH response in BPD are not secondary to dopamine.

Adult↗
PubMed1985

Subcellular fractionation of a hypercellulolytic mutant, Trichoderma reesei Rut-C30: localization of endoglucanase in microsomal fraction.

The growing mycelia of Trichoderma reesei Rut-C30 are richly endowed with endoplasmic reticula and a variety of pleomorphic subcellular bodies. Mycelia of the culture growing in presence of avicel pH101 was fractionated in sucrose density gradients, and several morphologically and biochemically distinct fractions were isolated. Mycelia were homogenized in a Bead Beater, and the homogenate was freed of nucleus and wall fragments by low-speed centrifugation before fractionation. Organelle-free cytosol, which did not penetrate the gradient, contained (of the total) 72% of the vanadate-sensitive ATPase, 26% of carboxymethyl cellulase (CMCase), 2% of cytochrome c reductase, and 13% of the protein. Significant fractions separated on a gradient were light vesicles containing heavily stained material inside and ribosomes attached to the outside surface, intact vesicles resembling condensing vacuoles, large vesicles derived from the plasma membrane, and heavy vesicles containing crystalline material. The light-vesicle fraction contained a large portion of the cell-bound CMCase activity. The particle-bound ATPase and cytochrome c reductase activities were concentrated in heavy fractions. The fractionation in the presence of MgCl2 improved the preservation of subcellular bodies derived from the endoplasmic reticula. Although the CMCase activity of the light-vesicle fraction was 4 times higher than the activity in the heavy-vesicle fraction, the CMCase antibody-binding capacities of both fractions were about the same. This discrepancy between the catalytic activity and the antibody-binding capacity suggests that the heavy vesicles might have contained considerable amount of inactive CMCase compared with that present in the light vesicles.

Cell Fractionation↗
PubMed1984

One day vs. two days of prophylactic antibiotics in patients undergoing major head and neck surgery.

Thirty patients undergoing major head and neck surgery were prospectively randomized to receive moxalactam (30 mg/kg) before surgery and for either 3 or 6 doses total postoperatively. Wound infection criteria were carefully specified and serum drug levels were monitored. Overall infection rate was 3%; the single infection occurred in a patient randomized to the 3 dose protocol. There was no statistically significant difference in infection rates between the two groups. Drug serum levels between the groups did not differ and none of the patients developed significant drug side effects. We conclude that short course prophylaxis is equally effective as more prolonged therapy. Our wound infection rate compares favorably with previous studies and supports the use of moxalactam as a prophylactive antibiotic in major head and neck surgery.

Adult↗
PubMed1983

Family medicine and family therapy: comparative development, methods, and roles.

Family medicine and family therapy have evolved separately, but the fields are now increasingly in contact with each other. Today's family physician needs a deeper grasp of their similarities and differences. This paper compares the two disciplines in terms of their (1) membership criteria for treatment, (2) considered appropriateness for treatment, (3) contractual process, and (4) evolution of membership over time. Also explored are the disciplines' notions of illness and change; their differing attitudes toward technique are analyzed as well. Family therapists and family physicians appear likely to have increased exposure to one another. As they do, common approaches may develop, and conceptual differences may present a mutual stimulus for growth and change.

Behavior Therapy↗
PubMed1978

Chronic effects of methadone on a line tilt generalization gradient in the pigeon.

Using an adjusting interval schedule, pigeons were trained to key peck at a relatively constant rate during 45 degrees line tilt presentations and at an extremely low rate in the presence of 0 degrees and 90 degrees line angles. Subsequently, the birds received intramuscular injections of methadone hydrochloride every 8 hr in doses beginning at 3 mg/kg/day and increasing progressively to 90 mg/kg/day. Stimulus generalization tests were run on the first day and on the last day a given dose was administered to assess the development of tolerance. Although chronic methadone treatment was associated with an overall decrement in key peck rate, the gradients of line tilt generalization were indistinguishable from saline control gradients at doses as high as 90 mg/kg/day. Though the birds exhibited gross behavioral incoordination, visual stimulus control appeared unaffected.

Animals↗
PubMed1978

Adrenarche: a survey of rodents, domestic animals, and primates.

The concentrations of the adrenal steroids dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and delta 4-androstenedione (delta 4-A) have been measured by RIA before and after sexual maturation in plasma of rodents, domestic animals, and primates to determine whether these species exhibit and adrenarchal process comparable to man. The average concentrations of DHA and DHAS were less than 60 ng/dl and 5 microgram/dl, respectively, in plasma of sexually mature rodents and domestic animals, and a significant increase in the plasma DHA level after sexual maturation was seen only in the rabbit and dog. The concentrations of DHA, DHAS, and delta 4-A in 21 rhesus monekeys from 0-3 yr of age were 2021 +/- 235 ng/dl (mean +/- SE), 357 +/- 60 microgram/dl, and 107 +/- 9 ng/dl, respectively, and did not increase during sexual maturation. By contrast, DHA, DHAS, and delta 4-A levels in plasma of chimpanzees were 5.9-fold, 3.3-fold, and 4.8-fold greater, respectively, in 7- to 22-compared to 0- to 3-yr-old animals. Temporally, the increase in DHA levels in the chimpanzee is apparent at 5 yr and this precedes the increase in gonadal steroids, as is characteristic of human adrenarche. It is apparent that adrenal androgen levels and their developmental patterns differ markedly among species, and that among the species examined, only the chimpanzee exhibits an adrenarche comparable to that of man.

Adrenal Glands↗