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Biomedical subjects

B Harmon

Publications and source records attributed to B Harmon.

At least 19 recordsLinked to original sources
PubMed2001

Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets.

Naive CD4+ T cells activated through TCR/CD28 under Th1 or Th2 conditions expressed canonical cytokine patterns irrespective of cell division. Only cells that had divided fewer than four times were capable of reexpressing alternative cytokines when restimulated under opposing conditions. Although T cells transcribed both IFN-gamma and IL-4 within hours in a Stat4-/Stat6-independent manner, neither T-bet nor GATA-3 was induced optimally without Stat signals, and polarized cytokine expression was not sustained. Cytokine genes were positioned apart from heterochromatin in resting T cell nuclei, consistent with rapid expression. After polarization, the majority of silenced cytokine alleles were repositioned to heterochromatin. Naive T cells transit through sequential stages of cytokine activation, commitment, silencing, and physical stabilization during polarization into differentiated effector subsets.

Alleles↗
PubMed2000

Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety).

The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.

Abdominal Pain↗
PubMed1999

Radiation-induced apoptosis and gene expression in neonatal kidney and testis with and without protein synthesis inhibition.

PURPOSE: To analyse the incidence of radiation-induced apoptosis, expression of two apoptosis-related genes, Bcl-2 and p53, and post-radiation levels of cell proliferation in the neonatal rat (4-5 days old) kidney and testis. MATERIALS AND METHODS: Apoptosis was quantified in control or treated kidney or testis at 2, 4, 6, 8 and 24h after 5 Gy of whole body X-irradiation (n=4 per group). Morphology (light and electron microscopy) and DNA gel electrophoresis were used to assess apoptosis. Temporal and spatial expression of Bcl-2 or p53 were analysed using immunohistochemistry. Administration of cycloheximide (1.5mg/kg) was used to determine whether new protein synthesis had a role in induction of apoptosis. Tritiated thymidine uptake and autoradiography were used to indicate alterations in cell proliferation (radiolabel administered 1 h prior to tissue collection) or S-phase cells undergoing radiation-induced apoptosis (radiolabel administered 1 h prior to irradiation). RESULTS: Apoptosis peaked at 4 h in the testis and 6 h in the kidney and was significantly higher in the renal nephrogenic zone than in the testis (p<0.05). Mitosis was almost completely negated after irradiation in both tissues. A higher proportion (almost fivefold) of the apoptotic cells died in S phase in the kidney than in the testis. Cycloheximide negated induction of apoptosis in the kidney, and markedly decreased apoptosis in the testis. Bcl-2 expression was highest in the differentiated zone of control kidneys and increased after irradiation in the nephrogenic zone, particularly near foci of apoptosis in developing nephrons. In the control testis, Sertoli cells had moderate expression of Bcl-2. After irradiation, there was complete absence of Bcl-2 expression in apoptotic Sertoli cells, with surviving cells increasing Bcl-2 expression. Irradiated kidney had more intense nuclear p53 expression compared with controls. In the testis, p53 that was present in controls continued to be expressed in surviving cells but not apoptotic cells in radiation-treated animals. CONCLUSIONS: Unique differences can be identified between the incidence and biomolecular control of radiation-induced apoptosis in the normal neonatal kidney and testis. These results may find application for minimizing damage to these normal neonatal tissues in the development of, for example, cancer treatment regimens.

Animals↗
PubMed1998

Transition metals as protease inhibitors.

An alternative approach to the development of clinically useful protease inhibitors was investigated. The approach utilized coordination chemistry of transition metal ions rather than substrate analogs to block active sites of these enzymes. In the case of serine proteases it was found that aqueous Ti(IV) is a potent inhibitor of the trypsin subclass, but not the chymotrypsin subclass. The direct binding of Ti(IV) to trypsin was made possible by the presence of a free carboxyl group at the bottom of the substrate binding pocket of the enzyme, and the five-coordinate geometry of TiO(SO4)(H2O). Although initial binding of Ti(IV) was reversible, it was followed in time by irreversible inhibition. Direct binding of octahedral or tetrahedral metal ion complexes was prevented by the inability of the enzyme active sites to promote formation of a five-coordinate transition state of the metal ion required for reaction. These studies demonstrate the ability of direct metal ion binding as a way to enhance blocking of enzyme active sites as compared with that of traditional organic inhibitors. Application of these findings was investigated by measuring the affect Ti(IV) had on growth of Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa. Five-coordinate titanyl sulfate completely inhibited the growth of these organisms. This suggests that five-coordinate titanyl sulfate, which is easier and less expensive to manufacture than conventional antibiotics, may be useful in controlling endemic infections of E. coli and S. typhimurium.

Binding Sites↗
PubMed1997

Cognitive and behavioral predictors of sexually transmitted disease risk behavior among sexually active adolescents.

OBJECTIVE: To identify important cognitive and behavioral predictors of sexually transmitted disease (STD) risk behavior among a sexually active adolescent cohort. DESIGN: One-year longitudinal study of health beliefs, sexual behaviors, and STD acquisition among 549 adolescents, 14 to 21 years of age. SETTING: School- and community-based health clinics in a large metropolitan area. PARTICIPANTS: Data from 410 sexually active adolescents completing surveys at baseline and 1-year follow-up. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Sexually transmitted disease risk behavior--a composite measure of condom use consistency with most recent sexual partner(s), number of vaginal sex partners, and frequency of intercourse with most recent sexual partner(s). RESULTS: For girls (n = 335), a model including baseline STD risk behavior, condom use self-efficacy, oral contraceptive use, communication with sexual partners about STD prevention, and alcohol use in connection with sexual activity explained 21.1% of the variance in STD risk behavior at 1-year follow-up. For boys (n = 75), the strongest predictors of STD risk behavior at follow-up included baseline STD risk behavior, perceived susceptibility to STD, condom use self-efficacy, negative outcome expectations associated with condom use, and perceived barriers to STD prevention. CONCLUSIONS: Efforts targeting reduction in STD risk behavior must begin before the onset of somewhat stable patterns of sexual risk behavior. Among adolescents who are sexually active, interventions should include components that increase condom use self-efficacy, build skills to communicate with sexual partners about STD prevention, and address behaviors associated with STD risk behavior including oral contraceptive use.

Adolescent↗
PubMed1996

Specific interactions of chromatin with the nuclear envelope: positional determination within the nucleus in Drosophila melanogaster.

Specific interactions of chromatin with the nuclear envelope (NE) in early embryos of Drosophila melanogaster have been mapped and analyzed. Using fluorescence in situ hybridization, the three-dimensional positions of 42 DNA probes, primarily to chromosome 2L, have been mapped in nuclei of intact Drosophila embryos, revealing five euchromatic and two heterochromatic regions associated with the NE. These results predict that there are approximately 15 NE contacts per chromosome arm, which delimit large chromatin loops of approximately 1-2 Mb. These NE association sites do not strictly correlate with scaffold-attachment regions, heterochromatin, or binding sites of known chromatin proteins. Pairs of neighboring probes surrounding one NE association site were used to delimit the NE association site more precisely, suggesting that peripheral localization of a large stretch of chromatin is likely to result from NE association at a single discrete site. These NE interactions are not established until after telophase, by which time the nuclear envelope has reassembled around the chromosomes, and they are thus unlikely to be involved in binding of NE vesicles to chromosomes following mitosis. Analysis of positions of these probes also reveals that the interphase nucleus is strongly polarized in a Rabl configuration which, together with specific targeting to the NE or to the nuclear interior, results in each locus occupying a highly determined position within the nucleus.

Animals↗
PubMed1996

Apoptosis and mitosis in oral and oropharyngeal epithelia: evidence for a topographical switch in premalignant lesions.

Apoptosis (programmed cell death) may play a part in carcinogenesis. The mucosa of the oral cavity, a common site for the development of dysplasia and squamous cell carcinoma, is ideal for the study of carcinogenesis in vivo. Earlier work suggested that apoptosis falls with the development of carcinoma, and that carcinogenesis is preceded by topographical changes in apoptosis. To explore these hypotheses, 72 paraffin sections were obtained: 15 normal (N), nine mild dysplasia (D), 15 severe dysplasia/carcinoma in situ (CIS), 30 squamous cell carcinoma (SCC: power analysis suggested 15 per group). Apoptotic (AI) and mitotic (MI) indices and AI/MI ratio were calculated (1000 cells/slide). These, with age, sex, alcohol and smoking habits, and anatomical subsite, were entered into a regression model with histological group as dependent. Vertical cell position (cp) was plotted, and resultant frequency curves were compared. MI significantly increased (mean N 0.39, 95% confidence interval 0-0.35; D 0.63, 0.23-0.98; SCC 0.86, 0.51-1.21, P < 0.0001) and AI/MI significantly decreased (D 0.54, 0.20-0.86; SCC 0.28, 0.05-0.61, P < 0.05) progressing from D, through CIS, to SCC. However, after inclusion of all variables, only MI remained significant (P < 0.0001). Peak incidence of mitosis shifted downwards in CIS relative to N and D, whilst peak apoptosis shifted upwards. Thus, programmed cell death remains static as mitosis increases in carcinogenesis of the oral cavity. However, there is an alteration in the topographical relationship of these events in CIS which may make homeostatic mechanisms involving apoptosis less efficient.

Adolescent↗
PubMed1992

American Indian--Alaska Native youth health.

OBJECTIVE: To assess risk behaviors, health problems, worries and concerns, and resiliency-promoting factors among American Indian-Alaska Native adolescents. DESIGN: Survey. SETTING: Nonurban schools from eight Indian Health Service areas. PARTICIPANTS: A total of 13,454 seventh- through 12th-grade American Indian-Alaska Native youths. MAIN OUTCOME MEASURES: revised version of the Adolescent Health Survey, a comprehensive, anonymous, self-report questionnaire with 162 items addressing 10 dimensions of health. RESULTS: Poor physical health was reported by 2% of the study sample and was significantly correlated with social risk factors of physical and/or sexual abuse, suicide attempts, substance abuse, poor school performance, and nutritional inadequacies. Injury risk behaviors included never wearing seatbelts (44%), drinking and driving (37.9% of driving 10th through 12th graders), and riding with a driver who had been drinking (21.8%). Physical and sexual abuse prevalence was 10% and 13%, respectively, with 23.9% of females reporting physical abuse and 21.6% of females reporting sexual abuse by the 12th grade. Almost 6% of the entire sample endorsed signs of severe emotional distress. Eleven percent of the teens surveyed knew someone who had killed himself or herself, and 17% had attempted suicide themselves. Sixty-five percent of males and 56.8% of females reported having had intercourse by the 12th grade. Weekly or more frequent alcohol use rose from 8.2% of seventh graders to 14.1% by the 12th grade; for males, the survey noted an increase in regular alcohol use of 3% to 5% a year to 27.3% by the 12th grade. For each variable measured, rates are much higher for American Indian adolescents than those for rural white Minnesota youth, except for age at first intercourse and alcohol use. CONCLUSIONS: American Indian-Alaska Native adolescents reported high rates of health-compromising behaviors and risk factors related to unintentional injury, substance use, poor self-assessed health status, emotional distress, and suicide. Interventions must be culturally sensitive, acknowledge the heterogeneity of Indian populations, be grounded in cultural traditions that promote health, and be developed with full participation of the involved communities.

Adolescent↗
PubMed1989

Deep vein thrombosis: a perspective on anatomy and venographic analysis.

Pulmonary thromboembolism affects 750,000 Americans annually. DVT is the primary origin of PE, which results in approximately 150,000 patient deaths annually. Normal variants affect the incidence of DVT. Patients with duplicated or fenestrated superficial femoral veins and patients with five or more valves are at increased risk for development of DVT. Positive contrast venography performed in the radiology department under fluoroscopic control remains the "gold standard" for the diagnosis of DVT, despite the development of other modalities. Low-osmolar contrast agents, either nonionic or dilute ionic, and postprocedure infusion of 2,500 U of heparin mixed in 150 mL of physiologic saline should be used to reduce the incidence of postphlebography DVT. Positive venographic signs of DVT include filling defect, cutoff, nonvisualization, and collateralization.

Humans↗
PubMed1984

An ultrastructural study on the "meconium corpuscles" in rat foetal intestinal epithelium with particular reference to apoptosis.

During the embryonic development of the intestine, programmed deletion of epithelial cells plays a vital role in the formation of secondary lumina and of villi. Electron microscopy shows that this deletion is effected by apoptosis, a distinctive mode of cellular death recently recognised as being implicated in normal tissue involution in the adult, as well as during intrauterine development. The process involves cellular condensation and budding to form membrane-bounded apoptotic bodies containing well-preserved organelles. These are then either engulfed by neighbouring principal cells or sloughed off into the intestinal lumen. Engulfed apoptotic bodies that show various degrees of lysosomal degradation have previously been referred to as "meconium corpuscles".

Animals↗
PubMed1982

Innervation of arteriovenous anastomoses in the web of the foot of the domestic duck, Anas platyrhynchos: structural evidence for the presence of non-adrenergic non-cholinergic nerves.

An analysis of the innervation of arteriovenous anastomoses in the web of the foot of the Pekin Duck (Anas platyrhynchos) was compared with the innervation of the right atrium of the duck heart using histochemical, ultrastructural and morphometric techniques, before and after 6OHDA. The presence of intense catecholamine fluorescence and nerve terminals containing typical noradrenergic small dense-cored vesicles, together with the absence of fluorescence and degeneration of noradrenergic terminals after 6OHDA, indicated the presence of a dense adrenergic innervation at the periphery of the anastomoses. Ultrastructural and histochemical data gave support to the presence of a cholinergic innervation. There was evidence that arteriovenous anastomoses were innervated by non-adrenergic, non-cholinergic nerves, viz. after 6OHDA, the mean diameter, mean percentage and mean density of granular vesicles in axon profiles associated with anastomoses (107 . 25 nm, 22 . 34% and 12 . 73 vesicles micron-2, respectively) were significantly higher (P less than 0 . 001) than values in the atrium (87 . 13 nm, 9 . 92% and 5 . 51 vesicles micron-2, respectively) and axons associated with anastomoses contained large granular vesicles ranging up to 210 nm in diameter. This non-adrenergic non-cholinergic innervation may represent the non-adrenergic non-cholinergic vasodilatory nerves shown by pharmacological methods to be present in the foot of the Pekin Duck.

Adrenergic Fibers↗
PubMed1980

Pressure standardized lumbar discography.

The basic procedure for carrying out clinical lumbar discography has been examined. As a consequence, a pressure-standardized injection technique has been established. It is shown that monitoring the flow of contrast medium into the disc can, in the case of a true nuclear injection, improve the diagnostic efficiency. Additionally, knowledge of this flow can help to avoid a commonly occurring, but not often recognized, artefact described in detail elsewhere (Quinnell and Stockdale, 1980).

Adult↗
PubMed1975

An electron-microscope study of the mode of cell death induced by cancer-chemotherapeutic agents in populations of proliferating normal and neoplastic cells.

Deletion of scattered single cells by ultrastructurally typical apoptosis was observed to take place continuously in the lining of the small intestinal crypts of normal mice, and in untreated Crocker mouse ascites tumours. Injection of the cancer-chemotherapeutic agents actinomycin D, mitomycin C, cytosine arabinoside and cycloheximide massively enhanced the rate of apoptosis in each situation, the morphology of cell death induced by these drugs being fundamentally different from that of coagulative necrosis, which developed without treatment in the centres of solid nodules that grew after subcutaneous inoculation of the tumour. In the crypt lining, where the predominant cell type affected appeared to be epithelial, the apoptotic bodies were either extruded into the lumen or rapidly phagocytosed and degraded by adjacent viable cells. But bodies in the ascites tumour were rarely ingested by uninvolved cells, presumably because of their wide dispersal in a fluid medium, and the stages in their development were seen more clearly than has been possible in solid tissues, where phagocytosis is ususlly rapid: they eventually underwent a change resembling coagulative necrosis or in-vitro autolysis. Reports suggesting that cancer-chemotherapeutic agents enhance autophagy in solid malignant neoplasms require confirmation, for secondary lysosomes of any sort were found to be uncommon in the treated ascites tumours, and there is little doubt that phagocytosed apoptotic bodies have been mistaken for autophagic vacuoles in the past. The significance of the fact that cancer-chemotherapeutic agents induce a type of cell death that is found in normal tissues is at present unknown.

Animals↗