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Biomedical subjects

K Bruce

Publications and source records attributed to K Bruce.

16 recordsLinked to original sources
PubMed2002

Tuberculosis in an indigenous young white south Wales population.

Concerns about tuberculosis in young people in two linked deprived non-metropolitan communities triggered an investigation into local disease incidence and control measures. A pragmatic case-finding exercise, epidemiological enquiry and DNA genotyping were carried out to establish incidence and connections between cases over a five-year period. Of the 91 cases identified, 88 were from the white indigenous population. Approximately one third of cases were aged under thirty. Eight disease clusters were identified. Epidemiological investigation found spurious links between these, and DNA genotyping was necessary to clarify links. Seven cases and several contacts had been in prisons throughout the United Kingdom. Index cases under thirty generated more contacts, more contacts needing prophylaxis and more secondary cases than older patients. The workload resulting from tuberculosis control in younger cases was considerable. Tuberculosis remains an important problem in this population.

Adolescent↗
PubMed2000

Anorexia in rats infected with the nematode, Nippostrongylus brasiliensis: experimental manipulations.

Nippostrongylus brasiliensis induces a biphasic anorexia in laboratory rats, the first phase coincident with lung invasion (ca day 2) and the second when the worms mature in the intestine (ca day 8). Using the anthelminthic, mebendazole (MBZ), N. brasiliensis infections of the rat were eliminated between the first and second anorexic episodes. This intervention prevented the expression of the second phase of anorexia. Rats exposed to a second infection with N. brasiliensis, 3 weeks after the primary infection, exhibited only a first phase anorexic response which was not influenced by MBZ termination of the primary infection. The lower cumulative food intake and weight gain of all infected rats after 8 days of infection were accompanied by elevated plasma insulin and, in some individuals, by elevated plasma leptin, compared with uninfected controls and previously-infected MBZ-treated rats. Messenger RNA levels for neuropeptide Y were higher in the hypothalamic arcuate nucleus of 8-day infected rats than in recovering MBZ-treated animals. Inoculation of rats with heat-killed N. brasiliensis larvae failed to induce anorexia and did not alter the severity of biphasic anorexia on subsequent injection of viable larvae. The first anorexic episode is therefore dependent upon viable migrating larvae. The second phase of anorexia clearly requires the continuing presence of the parasite beyond the lung phase. Viable migrating larvae are also required to confer 'resistance' to reinfection.

Animals↗
PubMed2000

Increased presence of eosinophilic granulocytes expressing transforming growth factor-beta1 in collagenous colitis.

BACKGROUND: Collagenous colitis is a disease characterized by chronic watery diarrhea, and on microscopic examination of colonic tissue, a typical thickening of the subepithelial collagen layer is seen. The etiology and pathophysiology behind this disease state are largely unknown. METHODS: We have used in situ hybridization and immunohistochemistry to study the expression of transforming growth factor (TGF) -beta1, a growth factor with the capacity to cause accumulation of collagen in tissues, in collagenous colitis. Colonic pinch biopsy specimens from a total of 34 patients were investigated: 17 patients with collagenous colitis and 17 controls. RESULTS: In patients with collagenous colitis there was increased expression of the TGF-beta1 gene compared with controls, as visualized by in situ hybridization. The vast majority of the TGF-beta1-expressing cells were eosinophils, both in collagenous colitis and controls, but there were also scattered fibroblastic and histiocytic stromal cells. Immunohistochemistry showed the presence of TGF-beta1, mainly in eosinophils, in the colonic mucosa. Morphometric quantification showed 603 +/- 192 eosinophils/mm2, (mean +/- standard error of the mean) in the colonic mucosa of patients with collagenous colitis compared with 30 +/- 7 eosinophils/mm2 in the controls. CONCLUSIONS: The present results suggest that eosinophils expressing TGF-beta1 may be of pathophysiologic importance in the connective tissue remodeling seen in collagenous colitis.

Adult↗
PubMed1999

Characterization and distribution of ferritin binding sites in the adult mouse brain.

Studies on iron uptake into the brain have traditionally focused on transport by transferrin. However, transferrin receptors are not found in all brain regions and are especially low in white matter tracts where high iron concentrations have been reported. Several lines of research suggest that a receptor for ferritin, the intracellular storage protein for iron, may exist. We present, herein, evidence for ferritin binding sites in the brains of adult mice. Autoradiographic studies using 125I-recombinant human ferritin demonstrate that ferritin binding sites in brain are predominantly in white matter. Saturation binding analyses revealed a single class of binding sites with a dissociation constant (K(D)) of 4.65 x 10(-9) M and a binding site density (Bmax of 17.9 fmol bound/microg of protein. Binding of radiolabeled ferritin can be competitively displaced by an excess of ferritin but not transferrin. Ferritin has previously been shown to affect cellular proliferation, protect cells from oxidative damage, and deliver iron. The significance of a cellular ferritin receptor is that ferritin is capable of delivering 2,000 times more iron per mole of protein than transferrin. The distribution of ferritin binding sites in brain vis-à-vis transferrin receptor distribution suggests distinct methods for iron delivery between gray and white matter.

Age Factors↗
PubMed1998

Nigrothalamic projections and nigrothalamocortical pathway to the medial agranular cortex in the rat: single- and double-labeling light and electron microscopic studies.

Although the rat medial agranular cortex (AGm) has been implicated in a variety of motor functions, the source of the afferents impinging upon thalamic neurons projecting to the AGm is not directly known. The main purpose of this study was to determine whether the AGm is a major recipient of the nigrothalamocortical pathway. This issue was addressed by two sets of experiments. First, the organization of the nigrothalamic projections was studied by light and electron microscopy following injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the pars reticulata of the substantia nigra (SNR). The major finding of this study was the disclosure of a heretofore unknown projection to the rostromedial part of the ventral anterior-ventral lateral complex (VAL). This projection originates exclusively from the ventral portion of the SNR and is comparable in strength to the well-known nigrothalamic projection to the ventromedial nucleus (VM). Electron microscopic examination revealed differences in the synaptic organization of nigral terminals in the VAL and the VM. A large proportion of the labeled terminals in the VAL was involved in axosomatic synapses, whereas, in the VM, the axosomatic synapses were rare, and 67% of nigral terminals were found in contact with thin dendrites. To assess a possible disynaptic nigrothalamocortical pathway to the AGm, a double-labeling strategy combining PHA-L injections in the SNR and pressure injections of the retrograde tracer, cholera toxin subunit B (CTB) in the AGm was employed. The greatest density of CTB-labeled neurons was found in the rostral and central portion of the VAL, coincident with the nigrothalamic labeling originating from the ventral SNR. Electron microscopic analysis confirmed that some of the PHA-L-labeled terminals established synaptic contacts with the CTB-labeled cell bodies and large dendrites. In conclusion, our findings indicate that there exist two different nigrothalamocortical pathways through the motor thalamus in the rat. The SNR-VAL-AGm cortical projection may play a role in oculomotor functions, whereas the SNR-VM-cortical pathway has been implicated in arousal mechanisms.

Animals↗
PubMed1997

Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma.

Recently, a human homologue of the Drosophila patched gene, PTCH, was identified as a putative tumor suppressor mutated in both hereditary and sporadic basal cell carcinomas. Because PTCH controls its own transcription, inactivating mutations in PTCH may lead to overexpression of mutant PTCH mRNA due to loss of autoregulation. The present study is aimed at evaluating whether deregulation of PTCH mRNA expression is a general feature of BCCs of varying histological growth pattern and malignant potential. Irrespective of histological subtype, PTCH mRNA was overexpressed consistently as determined by in situ hybridization in all of the sporadic (n = 16) and hereditary (n = 20) tumors examined. PTCH expression was found in all of the tumor cells but appeared stronger in the peripheral palisading cells. PTCH mRNA was not detected in adjacent nontumor epidermal cells or in other parts of the epidermis. In the majority of tumors (20 of 36), nuclear immunostaining for p53 was found in scattered cells, whereas seven tumors completely lacked p53 immunoreactivity. Our finding of an up-regulation of PTCH mRNA levels in all of the BCCs analyzed indicates that deregulation of the PTCH signaling pathway constitutes an early rate-limiting event in BCC development.

Adult↗
PubMed1997

Description of a novel plasmid replicative origin from a genetically distinct family of conjugative plasmids associated with phytosphere microflora.

A novel replicative origin (oriV) from a conjugative, mercury resistance plasmid (pQBR11, 304 kbp) has been cloned and sequenced. Homology to the pQBR11 oriV-containing 3.55 kbp BamHI fragment (pCV1200) was restricted to one of five genetically distinct classes (group I) of narrow host range, mega-plasmids that persist as a genetic component of the pseudomonad community indigenous to the microflora of sugar beet. The oriV of pQBR11 was located within a unique sequence of 300 bp which initiated the replication of pUC derived suicide vectors in Pseudomonas putida UWC1. The limited size of the DNA sequence required to initiate replication, and the presence of two 15/16 bp directly repeated motifs, indicate that this group of mega-plasmids contain a single origin of replication, which initiates replication via a host-polymerase dependent rolling circle mechanism.

Base Sequence↗
PubMed1997

Regulation of cellular Mg2+ by Saccharomyces cerevisiae.

Regulation of cellular Mg2+ by S. cerevisiae was investigated. The minimal concentration of Mg2+ that results in optimal growth of S. cerevisiae is about 30 microM and a half-maximum growth rate is attained at about 5 microM Mg2+. Since the plasma membrane has an electrical potential greater than 100 mV, passive equilibration of Mg2+ across the plasma membrane would provide sufficient cytosolic Mg2+ (0.1-1 mM). The total cellular Mg2+ of cells grown in synthetic medium containing 1 mM Mg2+ is about 400 nmol/mg protein, most of which is bound to polyphosphate, nucleic acids, and ATP. Total cellular Mg2+ decreases to about 80 nmol/mg protein as the Mg2+ in synthetic growth medium is reduced to 0.02 mM, but remains relatively constant in growth medium containing 1 to 100 mM Mg2+. Cells shifted into Mg(2+)-free medium continue to grow by utilizing the vacuolar Mg2+ stores. Mg(2+)-starved cells replenish vacuolar Mg2+ stores with a halftime of 30 min. following the addition of 1 mM Mg2+ to the growth medium. The data indicate that cytosolic Mg2+ is maintained by the regulation of Mg2+ fluxes across both the vacuolar and plasma membranes.

Biological Transport↗
PubMed1997

Collagenase-3 (MMP-13) is expressed during human fetal ossification and re-expressed in postnatal bone remodeling and in rheumatoid arthritis.

To explore possible physiologic functions for the metalloproteinase collagenase-3, we have examined its temporal and spatial expression during human fetal development. Except for mesenchymal cells in the umbilical cord at 4 weeks of gestation, signal for collagenase-3 mRNA was confined to mineralizing skeletal tissue and detected in hypertrophic chondrocytes and osteoblastic cells involved in ossification beginning at 10 weeks and continuing through gestation. These cells were also immunoreactive with collagenase-3 antiserum, indicating their ability to produce collagenase-3 protein. In osteoblastic cells, the expression of membrane-type 1 metalloproteinase and 72-kd gelatinase mRNA, which have the capacity to activate collagenase-3 in vitro, colocalized with that of collagenase-3. In postnatal tissues, collagenase-3 was re-expressed in processes involving skeletal remodeling, such as bone cysts and ectopic bone and cartilage formation. Multinucleated osteoclasts were consistently negative for collagenase-3. Furthermore, in patients with seropositive rheumatoid arthritis, expression of collagenase-3 was prominent in articular cartilage, and collagenase-3 protein was detected by immunoblotting in synovial fluids. Consistent with its substrate specificities, a plausible function for collagenase-3 in these processes is to preferentially degrade type II collagen, thus serving a role during primary ossification, in skeletal remodeling, and in destructive joint disease.

Aged↗
PubMed1996

Stromelysin-3 mRNA associated with myofibroblasts is overexpressed in aggressive basal cell carcinoma and in dermatofibroma but not in dermatofibrosarcoma.

Stromelysin-3 is produced in the stroma of various malignant tumors, and in breast carcinoma there seems to be a positive correlation between aggressive disease and intensity of stromelysin-3 expression, suggesting that stromelysin-3 participates in the tumor spread. In basal cell carcinoma, previous findings on stromelysin-3 have been inconclusive in this respect. Our study was undertaken to determine the pattern of stromelysin-3 production in relation to different histologic subtypes and stromal reactions in basal cell carcinoma. By in situ hybridization, stromelysin-3 mRNA was detected in stromal fibroblastic cells in 51/56 samples. Furthermore, there was a significant correlation between strong signal for stromelysin-3 mRNA and infiltrative tumor growth. In all tumors, there was ongoing collagen synthesis as shown by a signal for procollagen I mRNA; this signal co-localized with stromelysin-3 around tumor nests. Our findings suggest a link between stromelysin-3 and fibrotic stromal response, which prompted us to evaluate the expression of stromelysin-3 in other fibrotic skin tumors. Interestingly, stromelysin-3, co-localizing with procollagen I mRNA, was consistently expressed in lesional cells in dermatofibromas (19/19), but not in dermatofibrosarcomas (0/7). Thus, our results indicate that in addition to being a marker for malignant disease, stromelysin-3 is produced by fibroblastic cells associated with benign fibrosis. A subset of cells producing stromelysin-3 appears to be myofibroblasts as demonstrated by immunoreactivity for alpha smooth muscle actin in both basal cell carcinoma and dermatofibroma.

Actins↗
PubMed1994

Visualization of G1 chromosomes: a folded, twisted, supercoiled chromonema model of interphase chromatid structure.

We have used light microscopy and serial thin-section electron microscopy to visualize intermediates of chromosome decondensation during G1 progression in synchronized CHO cells. In early G1, tightly coiled 100-130-nm "chromonema" fibers are visualized within partially decondensed chromatin masses. Progression from early to middle G1 is accompanied by a progressive uncoiling and straightening of these chromonema fibers. Further decondensation in later G1 and early S phase results in predominantly 60-80-nm chromonema fibers that can be traced up to 2-3 microns in length as discrete fibers. Abrupt transitions in diameter from 100-130 to 60-80 nm along individual fibers are suggestive of coiling of the 60-80-nm chromonema fibers to form the thicker 100-130-nm chromonema fiber. Local unfolding of these chromonema fibers, corresponding to DNA regions tens to hundreds of kilobases in length, reveal more loosely folded and extended 30-nm chromatin fibers. Kinks and supercoils appear as prominent features at all observed levels of folding. These results are inconsistent with prevailing models of chromosome structure and, instead, suggest a folded chromonema model of chromosome structure.

Animals↗
PubMed1985

Rehabilitation of the disabled adolescent: experience with a local authority assessment centre.

School leavers and young adults who are severely physically disabled pose particular problems for habilitation and rehabilitation. A local authority unit, the Fourways Assessment Centre, has been providing a comprehensive service to this group of people for the past 10 years. Rather than operating as an independent self contained unit it has been closely integrated with the local authority social services and educational services.

Adolescent↗
PubMed1981

A computer program for distinctive feature analysis.

A computer program is described that will accomplish a distinctive feature analysis for speech misarticulations. The program, which is written in FORTRAN, is interactive in nature and is straightforward in design. It greatly facilitates the use of distinctive feature analysis in articulation training, as it reduces the time necessary to complete such an analysis from several hours to approximately 15 min.

Diagnosis, Computer-Assisted↗
PubMedDate not supplied

Notes on a light and electron microscopic double-labeling method combining anterograde tracing with Phaseolus vulgaris leucoagglutinin and retrograde tracing with cholera toxin subunit B.

Investigations of monosynaptic connections in the central nervous system have been hindered by the lack of compatible markers that can be used at both light and electron microscopic levels. In attempts to determine synaptic contacts between fibers originating in the substantia nigra and neurons projecting to the spinal cord, we have developed a double immunolabeling technique using anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde transport of unconjugated cholera toxin subunit B (CTB). In this report, we describe technical modifications which consistently produced superior labeling together with adequate ultrastructural preservation of the tissue and discuss the advantages of the two tracers.

Animals↗
PubMedDate not supplied

Quantitation of medullary astrogliosis in sudden infant death syndrome.

One of the few relatively consistent pathologic observations in sudden infant death syndrome (SIDS) is astrogliosis of the brain stem. Astrogliosis is a nonspecific reactive process and its cause in SIDS, although still uncertain, is postulated to be hypoxia-ischemia. In this study, the distribution of reactive astrocytes throughout the rostral-caudal extent of the medulla has been determined. Although astrogliosis was present throughout the length of the medulla, it reached a maximum at levels 50-75% of total length, with 0% at the pontomedullary junction. Counting every reactive astrocyte through serial sections of the medulla seems unwarranted in view of the nonspecificity of the astrocytic response. This report proposes a practical approach to the quantitation of reactive astrocytes in SIDS by examining a representative sample of medulla midway through its length.

Astrocytes↗