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Biomedical subjects

M L Turner

Publications and source records attributed to M L Turner.

At least 19 recordsLinked to original sources

Peripheral blood stem cell transplantation.

Haematopoietic stem cells are usually sessile within the bone marrow microenvironment. However, small numbers do circulate in the peripheral blood of normal individuals, and following chemotherapy and/or intravenous growth factors, a substantial transient rise in circulating stem cells occurs. Leukocytes harvested by cytapheresis at this time can be used for autologous reconstitution of the haematopoietic and lymphoid systems following high dosage chemo/radiotherapy for the treatment of malignant disease. Peripheral blood stem cell transplants give rise to similar disease response rates as autologous bone marrow transplants, but have the advantage of more rapid haematopoietic reconstitution, and in addition can be offered to patients in whom marrow harvest is not feasible due to bone marrow damage or infiltration. This article reviews the theoretical and historical background to haematopoietic stem cell research, current clinical practice in peripheral blood stem cell mobilisation and harvesting, addresses the potential advantages and disadvantages compared to bone marrow transplantation, and assesses current experience of comparative efficacy.

Animals

Effects of same-modality interference on immediate serial recall of auditory and visual information.

Two studies investigated the effects of same-modality interference on the immediate serial recall of auditorily and visually presented stimuli. Typically, research in which this task is used has been conducted in quiet rooms, excluding auditory information that is extraneous to the auditorily presented stimuli. However, visual information such as background items clearly within the subject's view have not been excluded during visual presentation. Therefore, in both the present studies, the authors used procedures that eliminated extra-list visual interference and introduced extra-list auditory interference. When same-modality interference was eliminated, weak visual recency effects were found, but they were smaller than those that were generated by auditorily presented items. Further, mid-list and end-of-list recall of visually presented stimuli was unaffected by the amount of interfering visual information. On the other hand, the introduction of auditory interference increased mid-list recall of auditory stimuli. The results of Experiment 2 showed that the mid-list effect occurred with a moderate, but not with a minimal or maximal, level of auditory interference, indicating that moderate amounts of auditory interference had an alerting effect that is not present in typical visual interference.

Acoustic Stimulation

Cell adhesion molecules: a unifying approach to topographic biology.

Cell adhesion molecules are pivotal to the development and maintenance of tissue structure in metazoan organisms. In mammals, several families of proteins are involved in cell-cell and cell-matrix adhesion. The cadherins are homophilic, primary CAMs, involved in the establishment of boundaries between cell collectives early in embryogenesis. The Ig gene superfamily have diversified widely, with homophilic and heterophilic CAMs and antigen recognition molecules amongst the members. The Integrin family play an important role in binding to extracellular matrix, as well as counter-receptors on the surface of other cells. The Selectin family and HCAM are carbohydrate-binding proteins, and play a prominent role in the circulation of lymphocytes and neoplastic cells. CAMs are fundamental to development of tissue structure in metazoan organisms. Cellular differentiation dictates adherence to a specific microenvironment, through the pattern of surface CAM expression. Conversely, CAM binding can affect gene expression within the cell itself. Cell differentiation and cell adhesion are interdependent processes. In the adult, CAM are crucial to tissue maintenance. Cells frequently change their adhesive properties in response to physiological or pathological processes. The integrity of the vascular system is maintained by circulating platelets which are capable of rapid upregulation of cell adhesion and profound changes in metabolism, on contact with subendothelial matrix. Both endothelial cells and neutrophils undergo changes in CAM expression in response to inflammatory mediators, permitting rapid and appropriate recruitment of phagocytes to damaged tissue. Tissue repair is dependent on phenotypic changes in normally static cells, allowing increased motility and replication. The immune system requires constitutive cells to undergo multiple complex adhesion and detachment events over short periods of time, and is capable of discriminating normal self from aberrant-self or non-self, through antigen specific recognition and adhesion molecules. The pathophysiology of processes such as infection and neoplasia are profoundly affected by cellular CAM expression. CAMs and related molecules are fundamental to the development, maintenance and surveillance of tissue structure.

Animals

General principles in the diagnosis and treatment of vulvar diseases.

There are several major considerations that compel us to regard the vulva in a special way. Its surface epithelium encompasses a range from mucosa, to keratinized glabrous skin, to keratinized, hair-bearing skin. It thus needs to be approached from the point of view of a dermatologist who has an interest in sexually transmitted diseases and mucosal pathology. Dermatologists have long dealt with another mucosal surface, the mouth, and there are numerous similarities between the two--witness several important orogenital syndromes. The vulva serves both sexual and obstetric functions, so disorders in this area naturally fall in the purview of the obstetrician-gynecologist. What we have attempted to do is to put forth a guide for evaluation and treatment of these patients that is essentially a combination of both approaches. In the authors' experience, we have learned a great deal from each other. We have learned to take a history, examine a patient, and eventually treat her with a combination of dermatologic and gynecologic modalities. If the dermatologist reading this article has become familiar with gynecologic techniques, and the gynecologist with dermatologic techniques, and they have learned when to apply each, we have accomplished our aim.

Diagnosis, Differential

Vulvar vestibulitis syndrome.

VVS is currently recognized as one of the leading causes of vulvodynia or chronic vulvar pain. Its cause is unknown, and it is defined by a constellation of signs and symptoms confined to the vulvar vestibule. Hence, there is introital or entry dyspareunia, vestibular erythema of varying degrees, and localized tenderness confined to the vulvar vestibule. It has been found to be associated with subclinical HPV infection; chronic, recurrent candidiasis; and persistent alteration of vaginal pH secretion, and therapy for some of these conditions sometimes leads to amelioration of the symptoms associated with vulvar vestibulitis. The majority of cases, however, are still idiopathic. The more chronic and severe cases are frequently helped by a surgical procedure that results in excision of most of the vestibule and advancement of the vaginal epithelium. Some of the milder cases are known to remit spontaneously, so conservative, supportive management is of the utmost importance.

Chronic Disease

Vulvar manifestations of systemic diseases.

As the study of vulvar diseases becomes more accepted and as physicians and patients become more comfortable discussing vulvar complaints, there will also be less hesitancy to examine the area adequately. This can only lead to better observations, more knowledge, and more exact diagnosis and treatment of these problems, whether they be primary in the vulva or part of a systemic process.

Acute Disease

An HIV positive haemophiliac with acute lymphoblastic leukaemia successfully treated with intensive chemotherapy and syngeneic bone marrow transplantation.

A 26-year-old HIV positive severe haemophiliac developed Burkitt-type acute lymphoblastic leukaemia with intracranial involvement. He underwent standard combination therapy, and entered complete remission. Syngeneic bone marrow transplantation (BMT) was undertaken; the donor was also HIV positive. The patient died 18 months from transplant of isolated intracranial relapse, with no evidence of systemic relapse. Unlike other types of non-Hodgkin's lymphoma, Burkitt's type occurs in HIV positive patients with relatively normal CD4 cell counts. Remission can be achieved using intensive chemotherapy, and since these patients may otherwise have a reasonable life expectancy, BMT may be appropriate.

Adult

Characterization of human loricrin. Structure and function of a new class of epidermal cell envelope proteins.

We have isolated and characterized a full-length cDNA clone encoding human loricrin. Curiously, this protein displays major differences from the recently described mouse loricrin (Mehrel, T., Hohl, D., Nakazawa, H., Rothnagel, J.A., Longley, M.A., Bundman, D., Cheng, C.K., Lichti, U., Bisher, M.E., Steven, A. C., Steinert, P.M., Yuspa, S.H., and Roop, D.R. (1990) Cell 61, 1103-1112). Although both proteins are glycine-serine-cysteine-rich, the sequences have not been conserved. However, analysis of the sequences reveals a common motif of quasi-peptide repeats of an aliphatic or aromatic amino acid residue followed by several glycine and/or serine and cysteine residues. These sequences are interspersed and flanked by short glutamine- or glutamine/lysine-rich peptides. Thus loricrins consist of a family of cell envelope proteins of highly variable sequences that nevertheless retain common structural elements. We show that unlike all other putative protein components of the cell envelope, loricrins are highly insoluble, due at least in part to cross-linking by disulfide bonds. Furthermore, we have isolated four peptides from purified human cell envelopes that contain recognizable loricrin sequences and which are cross-linked by the N epsilon-(gamma-glutamyl)lysine isodipeptide bond. The presence of such bonds thus affords an explanation for the extraordinary insolubility of loricrin by cross-linking to the cell envelope and can also explain the low steady-state levels of monomeric loricrin in cytoskeletal extracts of epidermis. This study represents the first report of this isodipeptide cross-link in a protein component of the cornified cell envelope. We propose a model for the structure of loricrin in which (i) the unusual glycine-serine-rich sequences adopt a flexible loop conformation, indexed on the recurrent aliphatic residues; (ii) inter- or intramolecular isodipeptide and disulfide cross-links induce or stabilize folding of loricrin so as to form a more compact rosette-like structure; and (iii) the presence of the flexible glycine-rich loops necessarily will impact a flexible character to the cell envelope and entire epithelium.

Amino Acid Sequence

Vulvar vestibulitis syndrome: an overview.

Vulvar vestibulitis syndrome is a constellation of symptoms and findings involving and limited to the vulvar vestibule that consists of: (1) severe pain on vestibular touch to attempted vaginal entry, (2) tenderness to pressure localized within the vulvar vestibule, and (3) physical findings confined to vulvar erythema of various degrees. Histopathologic findings are consistent with a chronic, nonspecific inflammatory response that is occasionally associated with metaplasia of the minor vestibular glands. The cause is likely multifactorial, and to date the syndrome has been seen in association with subclinical human papillomavirus, chronic recurrent candidiasis, chronic recurrent bacterial vaginosis, chronic alteration of vaginal pH, and the use of chemical and destructive therapeutic agents. Therapy is directed at elimination of these symptoms. When symptoms are unrelieved, a surgical approach consisting of vestibulectomy with vaginal advancement has a high rate of success.

Chronic Disease

Pudendal neuralgia.

We call attention to a group of patients with chronic vulvar burning (vulvodynia), who do not have apparent infections or easily discernible abnormal physical findings, but who on simple sensory testing have allodynia, hyperalgesia, hyperpathia, and hypoesthesia in varying permutations within the areas innervated by the pudendal nerve. We propose that pudendal neuralgia (pain along the pudendal nerve) is one of the causes of idiopathic vulvodynia. In those patients in whom a neurologic, metabolic, infectious, traumatic, or malignant cause for neuralgia is not found, medical management with tricyclic antidepressants, antiepileptic agents, or both may prove helpful. Awareness of this entity will lead to earlier diagnosis, treatment, and reassurance of patients with chronic vulvar burning.

Acyclovir

Repair of Achilles tendon ruptures with a polylactic acid implant: assessment with MR imaging.

An investigational tendon repair device composed of a polymer of lactic acid (PLA) is currently undergoing multicenter clinical trials for use in repairing rupture of the Achilles tendon. The advantages of the PLA device include high tensile strength and the induction of a rapid proliferative tissue response resulting in a shorter rehabilitation period than with conventional surgical repair. We reviewed 16 MR examinations performed in 10 patients 3-35 months after repair to characterize the MR appearance. All 16 T1-weighted sagittal images revealed a thickened fusiform tendon with streaks of moderate signal within the tendon corresponding to the PLA device and its surrounding collagenogenic response. The double-echo T2-weighted axial images at the mid tendon level demonstrated progressive changes in the signal pattern of the central portion of the tendon that reflected the maturation of the healing tendon. All tendons repaired with PLA implants were uniformly hypertrophied relative to the contralateral normal side because of the induced proliferative collagenogenic ingrowth. Two follow-up MR examinations were performed in six patients and showed mean reductions in tendon caliber of 24% and 30% at the mid and inferior levels. MR imaging of the Achilles tendon repaired with PLA implants shows a diffusely thickened tendon with streaks of signal within the tendon that distinguish it from tendons repaired by conventional techniques.

Achilles Tendon