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Biomedical subjects

A Thorpe

Publications and source records attributed to A Thorpe.

At least 19 recordsLinked to original sources

Benign prostatic hyperplasia.

In both ageing men and women, there is an increasing incidence of lower urinary tract symptoms (LUTS) which are increasing. These infections have many possible causes, including smooth muscle dysfunction, neurological factors and benign prostatic hyperplasia. Up to 15% to 25% of men aged 50-65 years have LUTS of sufficient severity to interfere with their quality of life. Although benign prostatic hyperplasia is an important cause of these symptoms, and can have serious consequences, clinicians should be aware of these other causes so that the appropriate diagnosis is made before invasive treatments are started. New medical treatments, including alpha-adrenergic blocking agents and 5 alpha-reductase inhibitors mean that many men without complications such as infection, bleeding, or chronic retention, and with mild to moderate symptoms, should be managed in primary care. Combined local protocols between primary and secondary care will help to establish which men with persistent symptoms or complications need referral for a urological opinion to determine the need for further investigation and more invasive forms of management. We review the pathophysiology of the disease, and current approaches to investigation and management of this common problem.

Cross-Sectional Studies↗

Comparison of CT and MRI in the pre-operative staging of rectal adenocarcinoma and prediction of circumferential resection margin involvement by MRI.

OBJECTIVE: It has been suggested that MRI may be used as the sole modality of choice in pre-operative staging in rectal cancers. Knowledge of tumour stage and a threatened Circumferential Resection Margin (CRM) pre-operatively are essential for planning neo-adjuvant therapy and as predictors of local recurrence. At present most units utilize CT scanning to assess these parameters. The aim of our study was two fold: firstly to examine the accuracy of preop CT and MRI staging of rectal cancers compared with final histology and secondly to assess the accuracy of MRI in predicting penetration of the mesorectal envelope (ME). PATIENTS AND METHODS: All patients with biopsy proven rectal adenocarcinoma underwent thin slice MRI and CT scan pre-operatively. Forty-seven patients have been prospectively entered into the study: 24 male (median age 68 years; range 38-91 years). Eleven patients were unsuitable for surgery leaving 36 patients available for study. RESULTS: CT correctly staged patients with T1/T2 rectal cancers more often than MRI (77% vs. 43%, P = 0.226). Patients with T1/T2 tumours were overstaged more often by MRI compared with CT (54% vs. 23%, P = 0.226). A greater proportion of patients with T3 tumours were correctly staged by MRI than CT (76% vs. 41%, P = 0.08); and more T3 disease was understaged by CT than MRI (54 vs. 18%, P = 0.032). CT and MRI staged T4 disease equally. In the assessment of mesorectal envelope integrity, MRI had a sensitivity of 80% and a specificity of 84%. The positive predictive value was 44% and the negative predictive value 96%. CONCLUSIONS: These results suggest significant differences between accurate pre-operative "T" staging by CT and MRI for rectal cancer. MRI has the potential however, to accurately assess mesorectal envelope invasion. Further analysis is required to assess whether MRI can be used as the sole modality in pre-operative staging of rectal cancers.

Adenocarcinoma↗

Neuropeptide co-localisation in the lepidopteran frontal ganglion studied by confocal laser scanning microscopy.

A comparative study of the co-localisation of three different families of neuropeptides, viz. allatostatins of the Y/FXFGL-NH(2) type, Manduca sexta allatostatin (Mas-AS) and allatotropin, in the frontal ganglion of lepidopteran larvae has been carried out by means of immunocytochemistry and confocal laser scanning microscopy. The simultaneous application of three types of fluorochrome-conjugated antibodies reveals triple co-localisation in an anterodorsal pair of neurones in the frontal ganglion of the noctuids Heliothis virescens and Lacanobia oleracea. There is no evidence of differential axonal transport, since all parts of these neurones show complete co-localisation of all three peptides. Prominent axons of the ganglionic neurones project in the recurrent nerve to the foregut and stomodeal valve. Over the crop, lateral and sub-lateral branches follow the course of circular muscle fibres and terminate in varicosities. All three neuropeptides have previously been shown to be myoregulatory on the foregut; the Y/FXFGL-NH(2) allatostatins and Mas-AS are inhibitory, whereas allatotropin is excitatory. The morphological evidence of co-localisation of physiologically antagonistic peptides within the same terminals suggests that an extremely complex mechanism controls the contractile activities of the foregut. A posterodorsal pair of neurones in the frontal ganglion have prominent axons projecting via the frontal connectives to the brain and in the recurrent nerve to the stomodeal valve where extensive branching suggests control over the valve movements. Studies of another noctuid, Spodoptera frugiperda, and the sphingid, M. sexta, show interesting variations in the co-localisation phenomenon.

Animals↗

Performance testing of three portable, direct-reading dust monitors.

Three portable direct-reading dust monitors were tested in a recirculating dust tunnel and a calm air dust chamber against a range of industrial dusts with different size distributions to investigate sources of variation in their responses. Responses were found to be linear compared to reference gravimetric respirable samplers over a range of concentrations for a particular particle size distribution. Their calibration factors were dependant on particle size, particle composition and air velocity. If particle size and air velocity do not change significantly then the calibration factor can be applied to the monitor readings to give an accurate measure of dust concentration. The DataRam and HAM, factory calibrated against respirable dust concentration, were found to agree closely, whereas the Microdust gave higher readings, having been factory calibrated against total suspended particulate concentration. The calibration of the DataRam was significantly altered by either contamination of the optics with dust or by cleaning the optics. This was not observed with either the Microdust or HAM, since both monitors include a reference calibration element.

Air Pollutants, Occupational↗

Morphological and physiological comparisons of two types of allatostatin in the brain and retrocerebral complex of the tomato moth, Lacanobia oleracea (Lepidoptera: Noctuidae).

The cellular localisation of two types of allatostatin in the brain and retrocerebral complex has been studied in larvae of Lacanobia oleracea (Noctuidae) using antisera against Manduca sexta allatostatin (Mas-AS) and two members of the Y/FXFGL-NH(2) allatostatin family. The axons of two groups of Mas-AS-immunoreactive neurosecretory cells in the pars lateralis form part of the nervi corporis cardiaci (NCC 1). They exit the brain as the combined NCC 1 and NCC 2 and pass through the corpora cardiaca (CC), where they divide to innervate the corpora allata (CA) and the mandibular (salivary) gland. The presence of Mas-AS immunoreactivity in the CA is consistent with the inhibitory action of this peptide on juvenile hormone (JH) biosynthesis in L. oleracea. Immunoreactivity in the mandibular gland nerve suggests an additional, as yet unidentified role for this peptide. Cells of the pars intermedialis, the main contributors to NCC 2, do not show Mas-AS immunoreactivity. The distribution of Y/FXFGL-NH(2) immunoreactivity is different from that of Mas-AS. Although there are fewer cells in the pars lateralis, immunoreactivity is observed in certain neurones of the pars intermedialis and the tritocerebrum. Axons of these latter neurones contribute to NCC 2 and NCC 3, respectively, and, combined with those from NCC 1, result in the prominent occurrence of Y/FXFGL-NH(2) immunoreactivity in the CC, particularly in the storage lobe. The CA has far less Y/FXFGL-NH(2) immunoreactivity compared with Mas-AS. In bioassays, the Y/FXFGL-NH(2) allatostatins did not inhibit JH synthesis by CA of L. oleracea.

Animals↗

Labour's century. One hundred years of solicitude.

The Labour Party made few policy statements on health before the First World War. Its only election pledge was to oppose compulsory vaccination in 1900. Growing awareness of North-South inequalities in health, and disparities in nutrition, prompted a greater interest in health services in the 1930s. Aspects of the NHS came under fire from within the Labour Party soon after 1948. Promises of extra spending in the 1960s and 1970s were inhibited by economic problems.

Health Expenditures↗

Triple co-localisation of two types of allatostatin and an allatotropin in the frontal ganglion of the lepidopteran Lacanobia oleracea (Noctuidae): innervation and action on the foregut.

The triple co-localisation of peptidergic material immunoreactive to antisera raised against allatostatins of the Y/FXFGL-NH2 type, Manduca sexta allatostatin (Mas-AS), and allatotropin has been demonstrated in a single pair of anterodorsal neurones in the frontal ganglion of the tomato moth, Lacanobia oleracea (Noctuidae). Another pair of posterior neurones contain only Y/FXFGL-NH2-type allatostatin immunoreactivity. The neurites of all four cells trifurcate, and axons project to the brain in the frontal connectives and to the foregut in the recurrent nerve. Axons from the anterior neurones, within the recurrent nerve, have prominent lateral branches supplying muscles of the crop, and axons from both anterior and posterior cells show profuse branching and terminal arborisations in the region of the stomodeal valve. The brain contributes Y/FXFGL-NH2-immunoreactive material, but not allatotropin or Mas-AS, to the recurrent nerve via NCC 1+2 and NCC 3. All three peptides have a reversible effect on the spontaneous (peristaltic) contractions of the foregut (crop) in vitro. Thus, both types of allatostatin are inhibitory at 10(-12) to 10(-7) M, whereas allatotropin is strongly myostimulatory at 10(-14) M. This is the first demonstration of the gut myoinhibitory effects of Mas-AS and, taken together with the effects of Y/FXFGL-NH2-type allatostatins and allatotropin, reveals a different functional aspect to that normally attributed to these three peptides, i.e. control of juvenile hormone synthesis by the corpus allatum.

Amino Acid Sequence↗

Sulfakinin neuropeptides in a crustacean. Isolation, identification andtissue localization in the tiger prawn Penaeus monodon.

The sulfakinin (SK) family of neuropeptides are characterized by a C-terminal octapeptide sequence that begins with two acidic residues (most commonly DD), and ends with YGHMRF-NH2, usually with the tyrosyl residue sulfated. So far, sulfakinins have only been identified in insects and the present study was initiated to investigate if the family is more widely distributed within the arthropods. Purification of an extract of the central nervous system of the giant tiger prawn Penaeus monodon has revealed three novel members of the sulfakinin peptide family. One of the peptides, Pem SKI, has the sequence <QFDEY(SO3H)GHMRF-NH2, where <Q denotes a pyroglutamic acid residue, and is for all criteria typical of insect sulfakinins, several of which also have an N-terminal pyroglutamic acid. Tyrosyl O-sulfation was verified by mass spectrometry. The two other peptides have a hitherto unknown L/M variation at position three from the C-terminus. One of these, Pem SKII, has a particularly glycine-rich N-terminus, AGGSGGVGGEYDDYGHLRF-NH2. The other, Pem SKIII, is a truncated form of Pem SKII, with the sequence VGGEYDDYGHLRF-NH2. Mass spectrometry of the latter two peptides indicated that only one of the two tyrosyl residues is sulfated. By analogy, it is suggested that the sulfation is located at the residue in position six from the C-terminus. A small amount of a nonsulfated variant of Pem SKII was also present in the extract. Immunocytochemical studies with sulfakinin antisera show a sparse neuronal distribution pattern, similar to that of insects. A prominent pair of large (approximately 25 micrometer) cells and 6-8 pairs of smaller (approximately 10 micrometer) cells are present in the protocerebrum. The larger cells have prominent neurites that give rise to varicosities in the centre of the brain. Their axons exit the brain via the circumoesophageal connectives and continue along the intersegmental connectives. Each of the thoracic and abdominal ganglia has sulfakinin-immunoreactive arborizations as a result of branching from the intersegmental nerves. This distribution pattern strongly suggests a role in neurotransmission or neuromodulation, although it remains to be elucidated what the exact role(s) is. However, on account of the conservation of peptide structure during the evolutionary period spanning the insect/crustacean lineage, especially between Pem SKI and insect sulfakinins, it may be assumed that the sulfakinins have a significant physiological role.

Amino Acid Sequence↗

Regulation of lepidopteran foregut movement by allatostatins and allatotropin from the frontal ganglion.

The frontal ganglion and associated neuronal pathways in larvae of the noctuid moth Helicoverpa armigera have been studied immunocytochemically with antisera against the endogenous neuropeptides, the allatostatins (helicostatins), and allatotropin. Two pairs of large ganglionic neurones contain allatostatin immunoreactivity, with the anteriormost of these pairs showing colocalisation with allatotropin. Allatostatin and allatotropin axons exit the frontal ganglion in the recurrent nerve and traverse the surface of the crop to give terminal arborisations around the stomodeal valve. There is a greater degree of lateral branching of allatotropin axons compared with allatostatin axons over the crop musculature. In vitro experiments show that the two types of peptides have antagonistic effects on the spontaneous myoactivity of the crop musculature. Allatotropin is myostimulatory at concentrations as low as 10(-16) M, enhancing both frequency and amplitude of peristaltic waves of contraction. All members of the helicostatin family inhibit peristalsis completely at concentrations of 10(-7)-10(-6) M and, to varying degrees, at 10(-10)-10(-8) M. On the basis of this evidence, it is suggested that peptidergic neurones of the frontal ganglion play a major part in regulating foregut motility through the antagonistic actions of the allatostatins and allatotropin.

Amino Acid Sequence↗

Characterisation of the helicostatin peptide precursor gene from Helicoverpa armigera (Lepidoptera: Noctuidae).

The gene encoding the helicostatin peptide family was isolated from a Helicoverpa armigera genomic DNA library. The deduced precursor sequence allowed unambiguous identification of all helicostatin peptides and verified the sequences of eight peptides previously isolated. The gene consists of at least three exons and encodes a precursor of 225 amino acids that contains three blocks of tandemly arranged helicostatin peptides including seven copies of the C-terminal sequence -YXFGL followed by a single Gly residue for carboxylamidation. Complete endoproteolytic processing at all possible dibasic cleavage sites would generate the seven helicostatin octapeptides previously purified from larval extracts. If processing was not complete at the third pair of basic amino acids the octadecapeptide (helicostatin IIa) would also be released. Two novel putative helicostatin peptide sequences were identified; YSKFNFGL and ERDMHRFSFGL, both of which had the C-terminal pentapeptide -FXFGL in place of the more usual -YXFGL sequence. Comparison of the helicostatin precursor with that of the cockroaches, locust and flies revealed variation in size, sequence and organisation of the 'allatostatin' precursors across different insect orders. In situ hybridisation histochemistry established that helicostatins are expressed in neurones of the central nervous system and endocrine cells of the midgut, indicating that the helicostatins are true brain-gut peptides. Northern blot analysis identified a single transcript of 1.6 kb in mRNA from whole larvae, isolated central nervous system and gut tissue.

Amino Acid Sequence↗

The place of bronchoscopic photodynamic therapy in advanced unresectable lung cancer: experience of 100 cases.

OBJECTIVES: The objectives of the study were: (1) to evaluate effectiveness of photodynamic therapy (PDT) for symptom palliation in patients with inoperable lung cancer; (2) to determine survival benefit in a subset of patients. METHODS: One hundred patients, 68 male, 32 female, aged 44-81 years (mean 62.5) with advanced inoperable bronchogenic cancer and endobronchial luminal obstruction were prospectively studied. Eighty-two percent had previous chemo/radiotherapy. The pre-treatment protocol consisted of: clinical, radiological and bronchoscopic examination, pulmonary function testing, assessment of WHO performance status and clinical staging. Treatment protocol was: intravenous injection of 2 mg/kg body weight of photofrin/polyhaematoporphyrin and interstitial illumination using 630 nm laser light 24-72 h later. Follow-up was at 6-8 weeks for 1 year. Then every 3-6 months if applicable. Repeat PDT as necessary. RESULTS: All patients were stage IIIa-IV. The histology of the tumour was: non small cell in 90 and small cell in 10. There was no treatment related mortality. Mean endoluminal obstruction fell from 85.8% to 17.5%, mean forced vital capacity (FVC) and forced expiratory volume in 1s (FEVI) improvement was 430 ml and 280 ml, respectively. Ninety patients died from 6 weeks to 37 months, mean and median survival: 9 months and 5 months, respectively. Ten patients are alive from 13 to 72 months, mean 36 months, median 29 months. Overall 2-year survival was 19%. Multivariant analysis indicated that age, sex, histology and stage of disease did not influence survival significantly but performance status did. Patients with WHO < 2 had mean and median survival of 17.8 and 14 months versus WHO > 2, 6.9 mean and 4 months median survival (log-rank P < 0.0001). CONCLUSIONS: (1) PDT is effective in palliation of inoperable advanced lung cancer. (2) Subset of patients with a better performance status have added survival benefit.

Adult↗

Monitoring of urban particulate using an electret-based passive sampler.

Site sampling trials have been carried out in the urban environment in order to assess the usefulness of a passive sampling device, originally developed for personal monitoring of airborne dust levels in industry. The sampling element is a small disc of electret material (polymer carrying a permanent electric charge) within a metal frame weighing approximately 15 g. The sampler is designed to capture particles by electrostatic attraction, in which case the capture rate depends on their electrical mobility but is independent of the rate at which air flows past the device. Passive samplers, along with miniaturized cascade impactors, have been exposed to urban particulate for periods of up to 28 days in locations with significantly different levels of airborne pollution. The cascade impactor data enabled good estimates to be made of PM10 and PM2.5 levels, and data from the passive sampler correlated with the total dust sampled by the impactor and with both the size fractions, that with the PM10 being better. Too few data have yet been obtained for its accuracy to be established, but it is unlikely that it will approach that of pumped samplers. It has been shown to be potentially useful for multiple, simultaneous site sampling and for monitoring personal environmental exposure situations in which dispensing with a power source is particularly useful. Being small, the sampler is easy to hide or camouflage, and because it is cheap, its loss or damage is not a serious matter.

Aerosols↗

Measurements of the effectiveness of dust control on cut-off saws used in the construction industry.

Materials used in the construction industry frequently contain large quantities of silica. When they are cut or shaped with power tools considerable respirable dust can be produced. Three dust control systems for use with cut-off saws have been evaluated on site: wet dust suppression using mains water, the same system using water from a portable water tank, and local exhaust ventilation. The efficiency of water suppression on cut-off saws has been precisely quantified in controlled laboratory conditions by means of measurements with and without dust control. When dust control was used on-site, the mean concentrations of airborne silica were reduced by a factor of between three and seven, the accuracy being limited by the relatively high limit of detection for silica. All controls systems generally reduced respirable dust levels by at least 90%. Although the effectiveness of dust suppression did not depend on blade type, a diamond blade was more effective than a resin-bonded blade with the pressurised water system; cutting a slab with this type of blade could be completed before the water tank required repressurization. In laboratory tests, the application of water reduced the dust concentration to < 4% of its value without control. The method for monitoring the dust concentration was sufficiently sensitive to measure a difference in concentration produced during cutting in different directions. It is important, however, that the pressure in supply reservoirs is properly maintained, that the water is correctly applied and that it is used at the correct rate. If this is done effective dust control can be achieved.

Construction Materials↗

Localization of allatostatin-immunoreactive material in the central nervous system, stomatogastric nervous system, and gut of the cockroach Blattella germanica.

Immunoreactivity against peptides of the allatostatin family having a typical YXFGL-NH2 C-terminus has been localized in different areas of the central nervous system, stomatogastric nervous system and gut of the cockroach Blattella germanica. In the protocerebrum, the most characteristic immunoreactive perikarya are situated in the lateral and median neurosecretory cell groups. Immunoreactive median neurosecretory cells send their axons around the circumesophageal connectives to form arborizations in the anterior neuropil of the tritocerebrum. A group of cells in the lateral aspect of the tritocerebrum project to the antennal lobes in the deutocerebrum, where immunoreactive arborizations can be seen in the periphery of individual glomeruli. Nerve terminals were shown in the corpora allata. These terminals come from perikarya situated in the lateral neurosecretory cells in the pars lateralis and in the subesophageal ganglion. Immunoreactive axons from median neurosecretory cells and from cells positioned in the anteriormost part of the tritocerebrum enter together in the stomatogastric nervous system and innervate foregut and midgut, especially the crop and the valve between the crop and the midgut. The hindgut is innervated by neurons whose perikarya are located in the last abdominal ganglion. Besides immunoreactivity in neurons, allatostatin-immunoreactive material is present in endocrine cells distributed within the whole midgut epithelium. Possible functions for these peptides according to their localization are discussed.

Amino Acid Sequence↗

Isolation and identification of multiple neuropeptides of the allatostatin superfamily in the shore crab Carcinus maenas.

20 neuropeptides belonging to the allatostatin superfamily were isolated from extracts of cerebral and thoracic ganglia of the shore crab Carcinus maenas. They were purified by HPLC, monitored by radioimmunoassay and identified by mass spectrometry and amino acid sequencing. The allatostatins are characterised by a common C-terminal pentapeptide sequence -YXFGL-NH2. Previously such peptides have only been reported from insects. In insects the variable post-tyrosyl residue is restricted to Ala, Asn, Asp, Gly or Ser. In C. maenas, however, there are only two types; thirteen of the peptides having a post-tyrosyl Ala and the other seven, a post-tyrosyl Ser. The crab peptides include the shortest allatostatins so far identified (YAFGL-NH2 and YSFGL-NH2) as well as the longest, a 27-residue peptide. The total of 20 peptides exceeds the highest number of allatostatins found in any of the insects investigated so far (14 in Periplaneta americana). It is of interest that, despite their clear homology, none of the peptides of C. maenas is identical to any of the more than 50 known insect allatostatins. The crab allatostatins show evidence of gene duplication and mutation that has resulted in several sub-groups with close structural similarities. For example, there are four heptapeptides with the common C-terminus -PYAFGL-NH2 that differ only at the N-terminal residue, which is either Glu, Asp, Asn or Ser. Other motifs, variously extended at the N-terminus, include -GPY(A/S)FGL-NH2 (three peptides), -DMY(A/S)FGL-NH2 (three peptides), and -GQY(A/S)FGL-NH2 (two peptides). Unique among the allatostatin superfamily, one of the crab peptides has a Tyr for Phe substitution at position three from the C-terminus (GGPYSYGL-NH2). Immunocytochemistry has provided clues to the functions of the allatostatins in crustaceans by showing their widespread presence in the central and stomatogastric nervous systems.

Amino Acid Sequence↗

Identification, tissue localisation and physiological effect in vitro of a neuroendocrine peptide identical to a dipteran Leu-callatostatin in the codling moth Cydia pomonella (Tortricidae: Lepidoptera).

A neuroendocrine peptide of the Leu-callatostatin family, LPVYNFGL-NH2, has been isolated from tissue extracts of 5th instar larvae of the codling moth, Cydia pomonella (Lepidoptera). It is identical to a peptide previously isolated from the blowfly, Calliphora vomitoria (Diptera). The distribution of this peptide within the tissues of C. pomonella has been mapped by immunocytochemistry using antisera raised against LPVYNFGL-NH2. Midgut endocrine cells contain Leu-callatostatin immunoreactivity, as do several paired Leu-callatostatin neurones in the brain and ventral nerve cord. Within the visceral nervous system, the frontal ganglion contains four Leu-callatostatin neurones. Axons from these cells combine with others originating from neurones in the brain and project within the nervi cardiostomatogastrici to innervate the tissues of the foregut. In particular, the oesophageal valve has a prominent ring of Leu-callatostatin-immunoreactive fibres. The synthetic peptide, LPVYNFGL-NH2, has a potent reversible inhibitory effect in vitro on all visible forms of spontaneous contractile activity of the foregut, including closure of the oesophageal valve. Complete myoinhibition is observed at peptide concentrations from 10(-10 )to 10(-16) M. These results, in conjunction with the results of similar studies on cockroaches, crickets and flies, suggest that the Leu-callatostatins are a ubiquitous family of insect neuroendocrine peptides with an important role in the control of gut motility.

Animals↗

Lepidopteran peptides of the allatostatin superfamily.

Peptides of the allatostatin superfamily with the C-terminal amino acid sequence -YXFGL-NH2 have been isolated and identified from the lepidopterans, the codling moth, Cydia pomonella (Tortricidae) and the bollworm, Helicoverpa armigera (Noctuidae). The peptides, designated cydiastatins and helicostatins respectively, were monitored during purification with radioimmunoassays based on the callatostatins of the blowfly Calliphora vomitoria. The eight peptides from each of the two species appear to form an homologous series with four identical and three that differ by a single amino acid. This study demonstrates the ubiquitous nature of this family of peptides in insects.

Amino Acid Sequence↗