Biomedical subjects

P Houghton

Publications and source records attributed to P Houghton.

At least 19 recordsLinked to original sources

PubMed1998

Medicinal plants and Alzheimer's disease: Integrating ethnobotanical and contemporary scientific evidence.

The use of complementary medicines such as plant extracts in dementia therapy, varies according to the different cultural traditions. In orthodox Western medicine, contrasting with that in China and the Far East for example, pharmacological properties of traditional cognitive or memory enhancing plants have not been widely investigated in the context of current models of Alzheimer's disease. An exception is Ginkgo biloba in which the ginkgolides have antioxidant, neuroprotective, and cholinergic activities relevant to Alzheimer's disease mechanisms. The therapeutic efficacy of Ginkgo biloba extracts in Alzheimer's disease in placebo-controlled clinical trials is reportedly similar to currently prescribed drugs such as tacrine or donepezil and, importantly, undesirable side effects of Ginkgo biloba are minimal. Old European reference books (eg, medical herbals) document a variety of other plants such as Salvia officinalis (sage) and Melissa officinalis (balm) with memory improving properties, and cholinergic activities have recently been identified in extracts of these plants. Precedents for modern discovery of clinically relevant pharmacological activities in plants with long-established medicinal use include, for example, the interaction of alkaloid opioids in Papaver somniferum (Opium poppy) with endogenous opiate receptors in the brain. With recent major advances in understanding the neurobiology of Alzheimer's disease, and as yet limited efficacy of so-called rationally designed therapies, it may be timely to re-explore historical archives for new directions in drug development. This article considers not only the value of an integrative traditional and modern scientific approach to developing new treatments for dementia, but also in the understanding of disease mechanisms. Long before the current biologically based hypothesis of cholinergic derangement in Alzheimer's disease emerged, plants now known to contain cholinergic antagonists were recorded for their amnesic and dementia-inducing properties.

Alzheimer Disease↗

PubMed1997

Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft.

A methylator-resistant human glioblastoma multiforme xenograft, D-245 MG (PR), in athymic nude mice was established by serially treating the parent xenograft D-245 MG with procarbazine. D-245 MG xenografts were sensitive to procarbazine, temozolomide, N-methyl-N-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, 9-aminocamptothecin, topotecan, CPT-11, cyclophosphamide, and busulfan. D-245 MG (PR) xenografts were resistant to procarbazine, temozolomide, N-methyl-N-nitrosourea, and busulfan, but they were sensitive to the other agents. Both D-245 MG and D-245 MG (PR) xenografts displayed no O6-alkylguanine-DNA alkyltransferase activity, and their levels of glutathione and glutathione-S-transferase were similar. D-245 MG xenografts expressed the human mismatch repair proteins hMSH2 and hMLH1, whereas D-245 MG (PR) expressed hMLH1 but not hMSH2.

Animals↗

PubMed1996

Associations between atlantoaxial and craniomandibular anatomy.

Roentgen-cephalometric studies have shown that anatomical features of the craniocervical junction are associated with head posture, cranial base angulation, and mandibular shape and growth. The aim of the present work was to study relationships between atlantoaxial and craniofacial morphology based on macroscopical observations of skeletal material derived from 38 prehistoric Polynesian and 53 prehistoric Thai people. The two uppermost cervical vertebrae and the mandible of each individual were studied macroscopically and each skull base was analyzed on cephalometric X-rays in lateral projection. The height of the atlantal anterior and posterior arches displayed a significant negative correlation with the cranial base angulation, in that the higher the arches the steeper the flexure between the sphenoidal/clival and clival/foraminal planes. None of the axial variables were associated with the cranial base angulation. The height of the atlantal posterior arch was also associated with the mandibular length, ramal height and gonial angle. Thus, in general, a high arch was seen in conjunction with a long, high and square shaped mandible, whereas a low arch was usually found together with a short and low mandible characterized by an obtuse jaw angle. The anterior height of the axis (vertebral mass + dens) was significantly associated with mandibular length and ramal height. It is suggested that these results are evidence of the intimate ontogenetic development of the atlas and the cranial base, and a reflection of the functional relationship between atlas and cranium.

Anthropology↗

PubMed1995

Asymmetry in the human skeleton. A study on prehistoric Polynesians and Thais.

Atlantal, long bone, and craniofacial measurements of prehistoric Polynesian and Thai skeletons were analysed to ascertain the extent and direction of bilateral asymmetry. The atlantal articular mass was constantly and significantly higher on the right side than on the left. In Thais, the midlongitudinal axis of the atlanto-occipital facet on the right side had a steeper inclination than that on the left. In both groups the dental occlusion was less mesial on the right side and the mandible was shorter, significantly so in the Thais. The long bones were more asymmetric in the Polynesians than in the Thais. Height asymmetry of atlas lateral tuberculum correlated inversely with mandibular ramal width asymmetry. Atlanto-occipital facet length asymmetry correlated with asymmetry of the gonial angle and facet angulation asymmetry correlated inversely with radial length asymmetry. Our results suggest a pervading asymmetry of skeletal structures which we ascribe as local adaptations to functional demands rather than as due to a uniform asymmetric growth pattern.

Animals↗

PubMed1994

Immunohistochemical analysis of the distribution of MyoD1 in muscle biopsies of primary myopathies and neurogenic atrophy.

The expression of the myogenic determination gene MyoD1 plays a primary role in the commitment of primitive mesenchymal cells to a striated muscle lineage and is down-regulated during later stages of differentiation. To determine the potential role of this gene in myopathic conditions, we examined its expression by means of immunohistochemical analysis, using a series of muscle biopsies from 14 patients with a variety of primary myopathies and neurogenic disorders. Utilizing the avidin-biotin-complex technique, cryostat sections were stained with monoclonal antibody 5.8 A, which we have previously described as having a high level of specificity for tumors with rhabdomyoblastic differentiation. Of special interest was the observation in 4 of 8 cases of neurogenic atrophy of varying levels of cytoplasmic positivity of muscle fibers, appearing to correlate with their degree of atrophy, in addition to weak nuclear staining. Muscle biopsies from 2 patients with Duchenne's muscular dystrophy and 2 patients with autoimmune inflammatory myopathies demonstrated various levels of nuclear positivity in scattered foci that appeared to correlate with areas of regeneration. A biopsy from a single case of neurogenic atrophy secondary to infantile spinal muscular atrophy (Werdnig-Hoffmann's disease) demonstrated diffuse but relatively weak staining of myofiber nuclei, in contrast to sections of normal striated muscle and muscle biopsies from patients with unexplained myoglobinuria, which exhibited only minimal amounts of staining. These data are compatible with observations that MyoD1 expression is related to electrical activity and muscle regeneration.

Adult↗

PubMed1994

The molecular basis of skeletal muscle differentiation.

In recent years, significant advances have been made in understanding the molecular mechanisms involved in the regulation of skeletal-muscle differentiation. This review focuses on the role of the MyoD family of myogenic transcription factors that includes MyoD, myf-5, myogenin, and MRF4 (herculin or myf-6) in myogenesis. Members of this family share sequence homology for the basic-helix-loop-helix (bHLH) regulatory motif. The basic domain is required for DNA binding, whereas the HLH domain is required for dimerization. The bHLH motif confers both properties of transcriptional activation of muscle specific genes and inhibition of cell growth through collaboration with the E2A gene products (E12 and E47) and the retinoblastoma gene product (pRB). The functions of the MyoD family can be suppressed through inhibition of their expression or activity by various factors. These include peptide growth factors (FGF and TGF-beta), immediate early gene products (Fos, Jun and Myc), other oncogene products (Ras, Src), the Id protein, and innervation. The use of gene-knockout animal models has shown that there is some degree of functional redundancy in that inactivation of either MyoD or myf-5 has no effect on muscle development, whereas inactivation of both genes results in an absolute lack of muscle cells. In contrast, the inactivation of myogenin alone results in mice with gross deficiency of mature muscle.

Animals↗

PubMed1993

Neandertal supralaryngeal vocal tract.

Interpretations of skeletal anatomy claiming to show that Neandertals could not have had a similar supralaryngeal vocal apparatus to that of humans are demonstrated to be flawed. Correction of the errors suggests that the Neandertal vocal apparatus need not have differed from that of recent humans.

Animals↗

PubMed1992

Desmin positivity in primitive neuroectodermal tumors of childhood.

In this report, we describe two rosette-forming primitive neuroectodermal tumors that were found to contain desmin by both immunohistochemistry and Western blotting. Electron microscopy on both cases was consistent with primitive neuroectodermal tumors and revealed that the tumor cells contained cytoplasmic bundles of intermediate filaments. In both cases, studies for MyoD1 protein using immunohistochemistry and Western blotting were negative. Thus, the detection of desmin in a pediatric neoplasm does not absolutely exclude the diagnosis of primitive neuroectodermal tumor and should not be considered as prima facie evidence that a small-cell tumor is a rhabdomyosarcoma.

Abdominal Neoplasms↗

PubMed1991

MyoD1 protein expression in alveolar soft part sarcoma as confirmatory evidence of its skeletal muscle nature.

A typical case of alveolar soft part sarcoma was found to express in a strong and widespread fashion the marker MyoD1 protein. This nuclear phosphoprotein is the product of a regulatory gene that controls the commitment of a cell to myogenic lineage; it therefore provides strong and perhaps definitive evidence in support of the skeletal muscle nature of this enigmatic neoplasm.

Cell Transformation, Neoplastic↗

PubMed1990

Polynesian face and dentition: functional perspective.

Widely dispersed throughout the Pacific, Polynesians are a biologically distinctive people in form and size of both body and head. Large-bodied and well-muscled, their body phenotype is suited to life in a thermolabile oceanic environment. Their craniofacial skeleton is large and robust, with mandibular size and form (the "rocker" mandible) being especially characteristic. In this paper the Polynesian variants of body form, and of facial size (including dentition) and form, are interpreted from a functional perspective.

Anthropometry↗

PubMed1990

An annual event.

Explore the source record for details and available documents.

Health Education↗

PubMed1989

Molecular differential pathology of rhabdomyosarcoma.

Tumors of the soft tissues are classified histogenetically according to their phenotypic resemblance to normal adult tissue. Here we describe molecular approaches that make it possible to distinguish between one class of these tumors, rhabdomyosarcoma, and other small-, round-cell tumors. We show that the ascertainment of specific genotypic changes can be used to distinguish further between the embryonal and alveolar subtypes of rhabdomyosarcoma. We tested our model in two ways: first, in a retrospective analysis of diagnostically problematic cases of undifferentiated, small-cell tumors and, second, in a blind study of pediatric tumors. Rhabdomyosarcoma was correctly identified in all cases using this strategy alone. The underlying simplicity of the strategy used to define rhabdomyosarcoma subtypes with molecular markers suggests a model by which tumors can be unequivocally identified, which may apply equally well to other human solid tumors.

Adolescent↗

PubMed1988

Validity and reliability issues in alternative patient classification systems.

The validity and reliability issues involved in using alternative patient classification systems were reviewed. Disease Staging and Patient Management Categories (PMCs) were applied separately and in conjunction with DRGs to three populations of patients drawn from a nine-hospital community data base. Data were examined with analyses that were as consistent as possible with hospital-based reviews of resource utilization. Questions focused on content and context validity (partially assessable by homogeneity), general and statistical reliability (measured by variance reduction), gaming, and cost. Ordinal stratifications were inconsistently produced, and improvement to DRGs' homogeneity was generally negligible. When used alone, staging produced only half the variance reduction of DRGs. PMCs, when used alone, appeared to produce sizeable variance reductions that may have been due to the large number of one- and two-case categories produced. Staging had category overlap, was expensive, and was unidimensional and subject to manipulation. PMCs had potentially serious logic problems, and both were inadequately documented. Neither system was considered appropriate for all needs, but each might work adequately under well-defined and limited conditions.

Diagnosis-Related Groups↗

PubMed1988

The effect of gastrin-releasing peptide on the endocrine pancreas.

Infusion of GRP into conscious sheep and dogs produced elevations of systemic plasma levels of insulin, glucagon, and pancreatic polypeptide (PP). In the dog, infusions of GRP produced dose-dependent decreases in plasma glucose levels, whereas, in the sheep, dose-dependent increases in plasma glucose levels occurred. Glucose turnover studies demonstrated that infusions of GRP produce prompt increases in the rate of appearance of glucose in sheep, but previous studies demonstrated a transient decrease in the rate of appearance of glucose in dogs, suggesting that sheep and dogs differ in hepatic responses to the elevated levels of insulin and glucagon. GRP was a potent PP secretagogue in the sheep, whereas, in contrast to results in the dog, infusions of GRP did not result in elevations of plasma levels of gastrin in sheep. GRP has multiple complex stimulatory effects on the endocrine pancreas, and there exist species-dependent differences in responses, which affect the potency and spectrum of the hormone-releasing activity of GRP. Further studies are required to determine the precise anatomical relation of GRP-containing nerve fibers to islet cells and to elucidate the pathways by which GRP activates endocrine pancreatic hormone release.

Animals↗

PubMed1987

The role of function in the development of human craniofacial form--a perspective.

As an anatomical region the head combines great diversity of function with close integration of structure. Consequently no structural component has autonomy of form. There is a sequence of maturation of functions and their related structural components, and in this sequence the nervous system and its supportive structures mature first. The nasal airway matures next in response to increasing body mass, and the masticatory system constitutes the last major functional system to reach maturity. The later the maturation of the function, the greater is the requirement for its related morphology to adapt to preceding skeletal templates. These matters of developmental sequence, and extrinsic as well as intrinsic craniofacial functions, are paramount considerations in interpreting the form of any component of head anatomy.

Face↗

PubMed1982

The Polynesian head: growth and form.

We consider the cranial base to be the primordial determinant of the head form and mandibular shape so common amongst (but not exclusive to) adult Polynesians. The flatness of the cranial base manifests its full influence only when growth of the upper facial skeleton is complete in early adulthood. We argue that during growth and maturation the upper facial skeleton and the maxillary occlusal plane are required to adjust in position to a major extent according to the template set out by the flat cranial base, with consequent obligatory and extreme adjustment in shape and position of the mandible in order that occlusion be maintained. The base is constrained from adjusting its own shape significantly by virtue of its intimate relationship with the brain and the emerging cranial nerves. The structural consequences of these adaptations are seen in the bony profile, which is vertically disposed and orthognathic, and in the large nasopharynx, while functionally the relative inefficiency of the mandible as a lever requires extensive compensatory development of masticatory musculature which influences the shape of the face and vault.

Adolescent↗

PubMed1981

Polynesian head form: an interpretation of a factor analysis of Cartesian co-ordinate data.

The three dimensional co-ordinates of a large number of landmarks on a series of Polynesian skulls have been obtained by means of a diagraph, and from standard lateral cephalograms. The method is accurate, and a very large amount of data is stored in the concise form of the standardized co-ordinates. A factor analysis of some of these data defines a number of distinct craniofacial segments showing independent variation in positioning, and therefore presumably growth, along defined axes. The segments thus defined relate well to the conclusions of other studies of skull growth and form, and support the view that the basis of cranial variation is the same for all Homo sapiens. It is suggested that the strict independence of the isolated craniofacial segments may be a consequence of the particular method, and may not truly reflect the situation in the growing skull.

Cephalometry↗

PubMed1978

Prehistoric New Zealanders.

The physical condition of prehistoric man in New Zealand is briefly surveyed. These were tall, robust Polynesian people living an active existence, and having an adequate diet. The mean life span of about 30 years for adults was short only by modern Western standards. A number of skeletal features, notably aspects of skull and long bone form, set them apart from other races of mankind.

Anthropology, Physical↗