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H Wood

Publications and source records attributed to H Wood.

At least 37 records · Page 2Linked to original sources
PubMed1994

The 5' end of yeast 5.8S rRNA is generated by exonucleases from an upstream cleavage site.

We have developed techniques for the detailed analysis of cis-acting sequences in the pre-rRNA of Saccharomyces cerevisiae and used these to study the processing of internal transcribed spacer 1 (ITS1) leading to the synthesis of 5.8S rRNA. As is the case for many eukaryotes, the 5' end of yeast 5.8S rRNA is heterogeneous; we designate the major, short form 5.8S(S), and the minor form (which is seven or eight nucleotides longer) 5.8S(L). These RNAs do not have a precursor/product relationship, but result from the use of alternative processing pathways. In the major pathway, a previously unidentified processing site in ITS1, designated A3, is cleaved. A 10 nucleotide deletion at site A3 strongly inhibits processing of A3 and the synthesis of 5.8S(S); processing is predominantly transferred to the alternative 5.8S(L) pathway. Site A3 lies 76 nucleotides 5' to the end of 5.8S(S), and acts as an entry site for 5'-->3' exonuclease digestion which generates the 5' end of 5.8S(S). This pathway is inhibited in strains mutant for XRN1p and RAT1p. Both of these proteins have been reported to have 5'-->3' exonuclease activity in vitro. Formation of 5.8S(L) is increased by mutations at A3 in cis or in RAT1p and XRN1p in trans, and is kinetically faster than 5.8S(S) synthesis.

Base Sequence↗
PubMed1994

Normal neurulation in mammals.

During mammalian neurulation regional differences are evident between the cranial region, in which neurulation is most complex, the trunk as far as the caudal neuropore and the secondary neurulation region of the caudal trunk plus tail. Differences among these three regions are characterized by specific patterns of morphogenesis and by specific patterns of gene expression. During cranial neurulation distinct regions develop in the brain and the presomitic hindbrain forms seven rhombomeric divisions. The first clear morphological boundary is the preotic sulcus (later transformed into the gyrus between rhombomeres 2 and 3), which may limit cell movement as neuroepithelial cells rostral to it flow towards and into the rapidly expanding forebrain region. The formation of rhombomeres as morphological entities and the development of a normal rhombomere-specific pattern of homeobox and other gene expression domains depend on relatively low levels of retinoic acid. Retinoic acid receptors, which are retinoic acid-activated transcription factors, and retinoid binding proteins, which control the availability of retinoic acid to the receptors, show regional patterns of expression in the cranial, trunk and caudal regions of the neuroepithelium during neurulation. These patterns suggest a possible mechanism for region-specific gene expression during neurulation.

Animals↗
PubMed1994

The association of swallowing dysfunction and aspiration pneumonia.

The medical literature has emphasized that aspiration of gastric contents or oral bacteria is a common cause of aspiration pneumonia. Swallowing disorders have been implicated in this disease but not studied at the time that aspiration pneumonia was diagnosed. A significant difference was found in the incidence of videofluoroscopically confirmed oropharyngeal swallowing problems in a group of patients diagnosed with aspiration pneumonia (AP) when compared with patients with nonaspiration pneumonia (NAP). Six of the 9 patients in the AP group aspirated during the videofluoroscopic evaluation and 2 others were considered to be at risk for aspiration. None of the 7 NAP patients demonstrated swallowing problems or aspiration. A significant difference in oral transit time also occurred between the two groups. Liquid was found to have a significantly faster oral transit time than paste or a cookie. Pharyngeal transit times were not found to be significantly different. Although there were only a small number of patients who met the criteria for this pilot study, a strong association was found between swallowing dysfunction and aspiration pneumonia.

Adult↗
PubMed1994

Genetic control of bacterial suicide: regulation of the induction of PBSX in Bacillus subtilis.

PBSX is a phage-like bacteriocin (phibacin) of Bacillus subtilis 168. Bacteria carrying the PBSX genome are induced by DNA-damaging agents to lyse and produce PBSX particles. The particles cannot propagate the PBSX genome. The particles produced by this suicidal response kill strains nonlysogenic for PBSX. A 5.2-kb region which controls the induction of PBSX has been sequenced. The genes identified include the previously identified repressor gene xre and a positive control factor gene, pcf. Pcf is similar to known sigma factors and acts at the late promoter PL, which has been located distal to pcf. The first two genes expressed from the late promoter show homology to genes encoding the subunits of phage terminases.

Amino Acid Sequence↗
PubMed1994

Exposure to retinoic acid before or after the onset of somitogenesis reveals separate effects on rhombomeric segmentation and 3' HoxB gene expression domains.

We have compared the relationship between the patterns of altered morphogenesis and of altered gene expression in mouse embryos exposed to excess retinoic acid (RA) (a) just before and (b) just after the onset of somitic segmentation (day 7.75 to day 8.25). Exposure to RA prior to the onset of somitic segmentation results in suppression of rhombomeric (but not somitic) segmentation, and conversion of the genetic identity of the whole preotic hindbrain to that of rhombomere 4. In contrast, exposure to RA at early somite stages results in near-normal rhombomeric segmentation; rhombomeric gene expression domains indicate that only rhombomere 2 has changed its genetic identity to that of rhombomere 4, the other preotic segments showing normal expression patterns for HoxB genes and Krox-20. The results indicate that RA has separable effects (1) on the genes mediating the process of rhombomeric segmentation per se, such as Krox-20, and (2) on the genes that influence the nature of the structures that subsequently develop from the individual rhombomeres, such as the Hox genes.

Animals↗
PubMed1992

Evolutionary conserved nucleotides within the E.coli 4.5S RNA are required for association with P48 in vitro and for optimal function in vivo.

E.coli 4.5S RNA is homologous to domain IV of eukaryotic SPR7S RNA, the RNA component of the signal recognition particle. The 4.5S RNA is associated in vivo with a 48kD protein (P48), which is homologous to a protein component of the signal recognition particle, SRP54. In addition to secondary structural features, a number of nucleotides are conserved between the 4.5S RNA and domain IV of all other characterised SRP-like RNAs from eubacteria, arachaebacteria and eukaryotes. This domain consists of an extended stem-loop structure; conserved nucleotides lie within the terminal loop and within single-stranded regions bulged from the stem immediately preceding the loop. This conserved region is a candidate for the SRP54/P48 binding site. To determine the functional importance of this region within the 4.5S RNA, mutations were introduced into the 4.5S RNA coding sequence. Mutated alleles were tested for their function in vivo and for the ability of the corresponding RNAs to bind P48 in vitro. Single point mutations in conserved nucleotides within the terminal tetranucleotide loop do not affect P48 binding in vitro and produce only slight growth defects. This suggests that the sequence of the loop may be important for the structure of the molecule rather than for specific interactions with P48. On the other hand, nucleotides within the single-stranded regions bulged from the stem were found to be important both for the binding of P48 to the RNA and for optimal function of the RNA in vivo.

Alleles↗
PubMed1992

Signal-sequence recognition by an Escherichia coli ribonucleoprotein complex.

Hydrophobic signal-sequences direct the transfer of secretory proteins across the inner membrane of prokaryotes and the endoplasmic reticulum membranes of eukaryotes. In mammalian cells, signal-sequences are recognized by the 54K protein (M(r) 54,000) of the signal recognition particle (SRP) which is believed to hold the nascent chain in a translocation-competent conformation until it contacts the endoplasmic reticulum membrane. The SRP consists of a 7S RNA and six different polypeptides. The 7S RNA and the 54K signal-sequence-binding protein (SRP54) of mammalian SRP exhibit strong sequence similarity to the 4.5S RNA and P48 protein (Ffh) of Escherichia coli which form a ribonucleoprotein particle. Depletion of 4.5S RNA or overproduction of P48 causes the accumulation of the beta-lactamase precursor, although not of other secretory proteins. Whether 4.5S RNA and P48 are part of an SRP-like complex with a role in protein export is controversial. Here we show that the P48/4.5S RNA ribonucleoprotein complex interacts specifically with the signal sequence of a nascent secretory protein and therefore is a signal recognition particle.

Bacterial Proteins↗
PubMed1992

Detection of occult lymph node metastases in malignant melanoma.

An accurate prediction of the prognosis of melanoma is dependent on the ability to determine the presence or absence of malignant cells in lymph nodes. Our laboratory has developed a method for screening lymph node sections for the presence of micrometastatic disease. The nodes obtained from regional lymphadenectomies are dissected free from surrounding tissue and divided into halves. One-half is subjected to routine histopathological evaluation and the other one-half is disrupted into a single cell suspension and placed into cell culture. Lymph nodes from 19 patients with malignant melanoma were evaluated by tissue culture. Tumor cells were isolated in 125 of the 173 nodes examined. In contrast, only 14 of these nodes were initially found positive for melanoma by routine pathological evaluation. All lymph nodes positive for melanoma by pathological evaluation were also culture positive. Examination by cell culture has led to an upgrade in the stage of disease in 58% of the histologically node-negative patients. In addition, 43% of the patients who were histologically node negative but culture positive have recurred, suggesting some clinical correlation. These results indicate that the tissue culture method for detecting micrometastatic lymph node disease may prove more reliable and sensitive than current techniques for determining the presence of occult melanoma.

Antigens, Neoplasm↗
PubMed1991

Induction of c-fos mRNA in cerebral cortex by excitotoxin stimulation of cortical inputs: involvement of N-methyl-D-aspartate receptors.

In this study we have characterized the induction of c-fos mRNA in cerebral cortex in response to unilateral kainate injection into the nucleus basalis. This treatment is associated with an intense stimulation of the ascending pathway and the subsequent induction of ornithine decarboxylase (ODC) enzyme activity and ODC mRNA in ipsilateral cerebral cortex which is sensitive to treatment with MK-801 and dihydropyridine antagonists. Unilateral injection of kainate into nucleus basalis caused a marked induction of c-fos mRNA in ipsilateral cortex which was detectable at 1 h, reached a maximal value at 8 h where c-fos mRNA levels were 16 times those in unoperated animals and then returned to control values by 24 h. However, the early induction of c-fos mRNA at 1 h was not related to a specific effect of kainate since at this time point, sham-operated animals also showed a significant increase in the level of c-fos mRNA in ipsilateral cerebral cortex. No significant induction of c-fos mRNA was detected in ipsilateral cortex in sham-operated animals at 4 and 8 h after injection of vehicle. Treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (3 mg/kg) significantly attenuated the response obtained at 4 h and 8 h after kainate injection by 73% and 55% respectively, but did not influence the level of c-fos mRNA induced at 1 h. Delaying administration of MK-801 by 30 min reduced the effectiveness of this treatment on the response obtained at 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Excitotoxin lesion of nucleus basalis causes a specific decrease in Go mRNA in cerebral cortex. Sensitivity to MK-801.

Lesions of the ascending cholinergic pathway from nucleus basalis are known to have profound effects on cortical function. In particular, a substantial potentiation of carbachol-stimulated polyphosphoinositide turnover is detected from 1 day after lesion and is maintained for several days before returning to normal by 1 month. In this study the effect of this lesion was investigated on levels of three G-protein alpha-subunit mRNAs. Excitotoxin lesion of the nucleus basalis caused a selective reduction in the levels of Go alpha mRNA in cerebral cortex ipsilateral to the lesion, Gs alpha and Gi alpha mRNA being unaffected. The maximal effect was obtained at 3 days after lesion where levels of Go alpha mRNA were decreased by 40% compared to sham-operated animals. Levels of Go alpha mRNA returned to normal values by 28 days. Treatment with MK-801 caused a significant attenuation of the decrease in Go alpha mRNA, indicating the involvement of NMDA receptors in this response.

Animals↗
PubMed1990

Induction of ornithine decarboxylase mRNA in cerebral cortex in response to kainate lesion of nucleus basalis: involvement of NMDA receptors.

Excitotoxin lesion of nucleus basalis with kainate or ibotenate results in degeneration of cholinergic neurones and a subsequent cholinergic deficit in cerebral cortex ipsilateral to the lesion. This lesion is accompanied by a massive increase in ornithine decarboxylase (ODC) activity in ipsilateral cortex, which was further investigated in this study by assay of levels of ODC mRNA in cerebral cortex after lesion. Injection of kainate into the nucleus basalis induced a significant increase in ODC mRNA in ipsilateral cerebral cortex which was maximal at 8 h after lesion and declined to control levels by 72 h. This induction showed clear regional specificity and was completely prevented by injection of an N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, at a dose of 1 mg/kg, 2 h after excitotoxin lesion. This study indicates that excitotoxin lesion causes an early and transient increase in ODC mRNA that is mediated by NMDA receptors and may represent a physiological response to injury.

Animals↗
PubMed1989

Well equipped.

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England↗
PubMed1986

Lysosomal elastase and cathepsin G in beige mice. Neutrophils of beige (Chediak-Higashi) mice selectively lack lysosomal elastase and cathepsin G.

A profound decrease in activities of the two lysosomal serine proteinases, elastase, and cathepsin G, was found in neutrophils of four independent beige mutants. Elastase and cathepsin G activities were assayed with the specific synthetic substrates MeO-Suc-Ala-Ala-Pro-Val-MCA and Suc-Ala-Ala-Pro-Phe-pNA, respectively. The defect is intrinsic to cells of beige mice, since transplantation of bone marrow from normal to mutant mice restored normal proteinase activity, and normal mice transplanted with beige marrow produced neutrophils with a deficiency of proteinase activity. The loss of elastase and cathepsin G activity was confirmed by separation of [3H]diisopropylfluorophosphate-labeled proteins on denaturing gels, which also revealed that other serine proteinases are at normal levels in beige neutrophil extracts. The deficiency of lysosomal proteinase activity appears specific, in that four other common neutrophil lysosomal enzymes, plus the spectrum of major neutrophil proteins are not affected by the beige mutation. The deficiency of proteinase activity is likely not the primary genetic alteration of the beige mutation, since more than one proteinase is affected, and heterozygous F1 mice have normal rather than intermediate levels of both proteinases. The lowered proteinase activity may contribute to the high susceptibility of beige mice and Chediak-Higashi patients to infection.

Animals↗