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Biomedical subjects

L Howe

Publications and source records attributed to L Howe.

At least 19 recordsLinked to original sources
PubMed2004

Guidelines for the management of periorbital cellulitis/abscess.

Orbital and periorbital swelling secondary to acute sinusitis is relatively common. Distinguishing between preseptal and orbital involvement can be difficult based on clinical observations alone. A delay in diagnosis and appropriate treatment may result in serious complications including blindness. The literature is reviewed and simple guidelines suggested to manage such patients, including their initial assessment, investigations with particular reference to the indications and timing of CT scanning, antimicrobial therapy and the type of surgery. These guidelines have been approved across disciplines in our unit and trialled successfully for 2 years.

Abscess↗
PubMed2002

A cat cloned by nuclear transplantation.

Sheep, mice, cattle, goats and pigs have all been cloned by transfer of a donor cell nucleus into an enucleated ovum, and now we add the successful cloning of a cat (Felis domesticus) to this list. However, this cloning technology may not be readily extendable to other mammalian species if our understanding of their reproductive processes is limited or if there are species-specific obstacles.

Animals↗
PubMed2001

Histone H3 specific acetyltransferases are essential for cell cycle progression.

Longstanding observations suggest that acetylation and/or amino-terminal tail structure of histones H3 and H4 are critical for eukaryotic cells. For Saccharomyces cerevisiae, loss of a single H4-specific histone acetyltransferase (HAT), Esa1p, results in cell cycle defects and death. In contrast, although several yeast HAT complexes preferentially acetylate histone H3, the catalytic subunits of these complexes are not essential for viability. To resolve the apparent paradox between the significance of H3 versus H4 acetylation, we tested the hypothesis that H3 modification is essential, but is accomplished through combined activities of two enzymes. We observed that Sas3p and Gcn5p HAT complexes have overlapping patterns of acetylation. Simultaneous disruption of SAS3, the homolog of the MOZ leukemia gene, and GCN5, the hGCN5/PCAF homolog, is synthetically lethal due to loss of acetyltransferase activity. This key combination of activities is specific for these two HATs because neither is synthetically lethal with mutations of other MYST family or H3-specific acetyltransferases. Further, the combined loss of GCN5 and SAS3 functions results in an extensive, global loss of H3 acetylation and arrest in the G(2)/M phase of the cell cycle. The strikingly similar effect of loss of combined essential H3 HAT activities and the loss of a single essential H4 HAT underscores the fundamental biological significance of each of these chromatin-modifying activities.

Acetylation↗
PubMed2001

Recruitment of HAT complexes by direct activator interactions with the ATM-related Tra1 subunit.

Promoter-specific recruitment of histone acetyltransferase activity is often critical for transcriptional activation. We present a detailed study of the interaction between the histone acetyltransferase complexes SAGA and NuA4, and transcription activators. We demonstrate by affinity chromatography and photo-cross-linking label transfer that acidic activators directly interact with Tra1p, a shared subunit of SAGA and NuA4. Mutations within the COOH-terminus of Tra1p disrupted its interaction with activators and resulted in gene-specific transcriptional defects that correlated with lowered promoter-specific histone acetylation. These data demonstrate that the essential Tra1 protein serves as a common target for activators in both SAGA and NuA4 acetyltransferases.

Acetylation↗
PubMed2001

T-cell contributions to alveolar bone loss in response to oral infection with Porphyromonas gingivalis.

We have previously shown that mice lacking CD4+, but not CD8+, T cells lose less alveolar bone loss in response to oral infection with Porphyromonas gingivalis than do immunocompetent mice of the same genetic background, indicating that CD4+ T cells contribute to bone resorption. The CD4+ and CD8+ T-cell knockouts were produced by targeted deletions of, respectively, major histocompatibility complex II (MHCII) or beta2-microglobulin (producing non-expression of MHCI). Because MHC deletions can have other effects in addition to those on T-cell selection, we wanted to confirm that the lessened bone loss was truly an effect of the lack of T cells. Consequently, we repeated our experiments with C57B1 /6J-Tcra mice that have a targeted deletion of the alpha chain of the T-cell receptor (Tcra). Six weeks after oral infection with P. gingivalis ATCC 53977 the total bone loss at buccal maxillary sites was 0.28 mm in infected immunocompetent mice (P=0.002 compared with sham-infected mice), whereas in Tcra knockouts the bone loss was only 0.08 mm (P=0.04 compared with shams). The T-cell-deficient mice thus lost 70% less bone after infection than did genetically matched immunocompetent mice (P =0.003). These experiments confirm that T cells, and their responses to oral infection with P. gingivalis, help to push bone remodeling in the direction of net loss of bone.

Alveolar Bone Loss↗
PubMed2000

The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex.

We have purified and characterized a Gcn5-independent nucleosomal histone H3 HAT complex, NuA3 (Nucleosomal Acetyltransferase of histone H3). Peptide sequencing of proteins from the purified NuA3 complex identified Sas3 as the catalytic HAT subunit of the complex. Sas3 is the yeast homolog of the human MOZ oncogene. Sas3 is required for both the HAT activity and the integrity of the NuA3 complex. In addition, NuA3 contains the TBP- associated factor, yTAF(II)30, which is also a component of the TFIID, TFIIF, and SWI/SNF complexes. Sas3 mediates interaction of the NuA3 complex with Spt16 both in vivo and in vitro. Spt16 functions as a component of the yeast CP (Cdc68/Pob3) and mammalian FACT (facilitates chromatin transcription) complexes, which are involved in transcription elongation and DNA replication. This interaction suggests that the NuA3 complex might function in concert with FACT-CP to stimulate transcription or replication elongation through nucleosomes by providing a coupled acetyltransferase activity.

Acetyltransferases↗
PubMed2000

The many HATs of transcription coactivators.

Histone acetylation is closely linked to gene transcription. The identification of histone acetyltransferases (HATs) and the large multiprotein complexes in which they reside has yielded important insights into how these enzymes regulate transcription. The demonstration that HAT complexes interact with sequence-specific activator proteins illustrates how these complexes target specific genes. In addition to histones, some HATs can acetylate non-histone proteins suggesting multiple roles for these enzymes.

Acetyltransferases↗
PubMed1999

Dental implants. 7. Basic restorative techniques.

Some restorative techniques for implant supported restorations will be familiar to dentists used to providing conventional crown and bridgework. The differences and principles involved when using implants are identified.

Dental Abutments↗
PubMed1999

Myers Briggs Type Indicator and Tridimensional Personality Questionnaire differences between bipolar patients and unipolar depressed patients.

OBJECTIVES: The current study was designed to compare personality differences between bipolar patients and unipolar depressed patients, as evaluated on the Myers Briggs Type Indicator (MBTI) and the Tridimensional Personality Questionnaire (TPQ). METHODS: A group of bipolar and a group of unipolar depressed patients filled out the MBTI, the TPQ, the Beck Depression Inventory, and the CAGE questionnaire. The two groups were compared with each other as to responses on the above surveys, and subgroups of bipolar depressed and bipolar patients with manic symptoms were also compared. RESULTS: Bipolar patients were found to be significantly more extroverted (p = 0.004) and less judging (p = 0.007) on the MBTI. They were significantly more novelty seeking (p = 0.004) and less harm avoidant (p = 0.002) on the TPQ. Of the above differences, only the TPQ harm avoidance scale appeared strongly linked to the patients' level of depression. CONCLUSION: Significant differences in personality exist between bipolar disorder and unipolar depressed patients.

Adult↗
PubMed1999

Mucinase and sialidase activity of the vaginal microflora: implications for the pathogenesis of preterm labour.

Evidence linking bacterial vaginosis (BV) to chorioamnionitis and spontaneous preterm birth is mounting. Successful treatment of BV could reduce the rate of late miscarriage and preterm birth. Mucinase and sialidase activity have been implicated in the pathogenesis of BV. This study extends the work of previous studies to investigate sialidase, other known mucin degrading enzymes and overall mucin degrading activity in samples of vaginal fluid from women with and without BV. Samples from 31 women were diagnosed for BV, and tested for enzyme activity using established assays. Activity was recorded in all samples. Significant increases in activity were detected in BV samples for sialidase using a mucin (BSM P<0.005) and serum type glycoprotein (AGP P<0.005) substrates, beta-galactosidase (P<0.001), and beta-N-acetylhexosaminidase (P<0.01). No significant increases in BV patients were detected in O-glycanase, proteinase, arylesterase, sulphatase or whole mucinase activities. These results support the hypothesis that certain BV-associated enzymes may detrimentally affect the mucosal barrier, permitting bacteria access to the uterus.

Bacterial Proteins↗
PubMed1999

Histone acetyltransferase complexes and their link to transcription.

Early studies revealing the relationship between the state of histone acetylation and gene transcription were largely indirect. Increasing information regarding the enzymes that catalyze transcription linked acetylation is beginning to clarify this issue. This review attempts to relate previous data regarding the distribution of histone acetylation within different chromatin regions with recent data regarding the substrate specificity, subunit composition, and recruitment of the known histone acetyltransferase complexes.

Acetyltransferases↗
PubMed1999

Time-resolved studies of the excited-state dynamics of meso-tetra(hydroxylphenyl)chlorin in solution.

Meso-tetra(hydroxyphenyl)chlorin (m-THPC) is a new photosensitizer developed for potential use in photodynamic therapy (PDT) for cancer treatment. In PDT, the accepted mechanism of tumor destruction involves the formation of excited singlet oxygen via intermolecular energy transfer from the excited triplet-state dye to the ground triplet-state oxygen. Femtosecond transient absorption measurements are reported here for the excited singlet state dynamics of m-THPC in solution. The observed early time kinetics were best fit using a triple exponential function with time constants of 350 fs, 80 ps and > or = 3.3 ns. The fastest decay (350 fs) was attributed to either internal conversion from S2 to S1 or vibrational relaxation in S2. Multichannel time-resolved absorption and emission spectroscopies were also used to characterize the excited singlet and triplet states of the dye on nanosecond to microsecond time scales at varying concentrations of oxygen. The nanosecond time-resolved absorption data were fit with a double exponential with time constants of 14 ns and 250 ns in ambient air, corresponding to lifetimes of the S1 and T1 states, respectively. The decay of the T1 state varied linearly with oxygen concentration, from which the intrinsic decay rate constant, ki, of 1.5 x 10(6) s-1 and the biomolecular collisional quenching constant, kc, of 1.7 x 10(9) M-1 s-1 were determined. The lifetime of the S1 state of 10 ns was confirmed by fluorescence measurements. It was found to be independent of oxygen concentration and longer than lifetimes of other photosensitizers.

Antineoplastic Agents↗