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Biomedical subjects

D Wilson

Publications and source records attributed to D Wilson.

At least 289 records · Page 16Linked to original sources

Non-medical implications of malignant melanoma.

Insurance and mortgage companies continue to regard melanoma in a rigid and perhaps flawed way, with detrimental effect to patients' financial standing. We questioned 100 consecutive patients coming to our clinic between the ages of 20 and 50, and asked if they had had problems obtaining life insurance, mortgages etc, since they were diagnosed. A substantial proportion of patients in the younger age groups had problems with mortgage and insurance applications.

Adult↗

Lipidized medulloblastoma in adults.

We describe the clinical, imaging, histologic, immunohistochemical, and ultrastructural features as well as the DNA ploidy analysis of two primitive neuroectodermal neoplasms demonstrating prominent cytoplasmic lipid accumulation originating in the posterior fossa of adults. These two tumors most likely exemplify a variant of medulloblastoma with heavily lipidized cells and support the postulated pluripotentiality of primitive neuroectodermal neoplasms. Recognition of this entity as a phenotypic variant of medulloblastoma will militate against diagnostic confusion with other entities that may contain cells with lipoblastic or adipocytic differentiation.

Cerebellar Neoplasms↗

Decreased weight gain in BB rats before the clinical onset of insulin-dependent diabetes.

Inbred specific pathogen-free diabetes-prone (DP) and diabetes-resistant (DR) BB rats were crossed to produce F1 and intercrossed to produce F2 rats. Diabetes segregates in these crosses as a recessive trait on rat chromosome 4. The weight gain of genetically diabetes-prone rats born to F1 healthy parents was studied to avoid effects of maternal diabetes. The weight gain of the F2 rats was initially not different from the F1 parents. The F2 rats later developing diabetes grew in parallel with their non-affected siblings up until the last 9 days before onset. During these 9 days they showed a decreased weight gain compared to their healthy litter-mates regardless of age. We conclude that decreased weight gain precedes the abrupt clinical onset of diabetes in BB rats and that it may be due to processes associated with the selective loss of beta cells.

Aging↗

The prevalence of oestrogen replacement therapy in South Australia.

OBJECTIVE: To ascertain the prevalence of the use of oestrogen replacement therapy in the South Australian community. DESIGN AND SETTING. Data was collected as part of the South Australian Health Omnibus Survey which involved a clustered, self-weighting, multi-stage, systematic representative area sample of 4608 households in metropolitan and country South Australia. One-thousand and forty-seven women over the age of 40 were personally interviewed by trained data collectors. OUTCOME MEASURES: Demographic characteristics, prevalence of current or past oestrogen use, type of oestrogen used, period of use and reasons for using, stopping or never using therapy. RESULTS: Current use of oestrogen replacement therapy is 13.6% and ever use was 24.3%. The highest prevalence of use was in the age group 45-54 years. Use of oestrogen replacement therapy associated with women born in the UK or Ireland, middle income earners, intermediate education, recent visits to a general practitioner, a current relationship, previous hysterectomy and smoking. The commonest period of use for current users was 1-5 years and the longest 30 years. In contrast many past users had stopped within 6 months, usually because of side effects. The commonest reasons for oestrogen use were to alleviate symptoms, 'following hysterectomy' and to prevent osteoporosis. Only 4.3% took oestrogen to reduce the risk of heart attack or stroke. Reasons for not taking therapy were often due to the woman being premenopausal, having no symptoms or ignorance of the therapy. CONCLUSION: Nearly one quarter of women over the age of 40 have used oestrogen replacement therapy. In general there is a perception only of the short term benefits amongst the current users and there is misinformation amongst the non-users. Therapy is often stopped after a very short time because of minor side effects.

Adult↗

The effects of intraarticular administration of hyaluronan in a model of early osteoarthritis in sheep. I. Gait analysis and radiological and morphological studies.

Using a model of early osteoarthritis (OA) induced in ovine joints by medial meniscectomy, the intraarticular effects of two hyaluronic acid (HA) preparations (AHA and DHA) were investigated. DHA was an HA preparation with an average molecular weight (MW) of approximately 2.0 x 10(6) d, and AHA had a MW of approximately 8 x 10(5) d. Animals (n = 5) were injected intraarticularly with 1 mL (10 mg/mL) of either HA preparation once a week for 5 weeks beginning 16 weeks after initiation of arthropathy. Meniscectomized, saline (1.0 mL)-injected animals (n = 5) and nonoperated sheep (n = 5) were used for controls. Force-plate analysis of gait and radiographic changes in joints were evaluated in these groups before and after intraarticular treatment. At necropsy, cartilage gross morphology, osteophyte development, and cartilage histopathology were examined. Meniscectomized joints were characterized by erosions and fissuring of cartilage of the medial compartment with areas of decreased matrix staining for proteoglycans. Osteophytes were present at the medial joint margins. Saline-treated meniscectomized animals showed reduced loading of the operated limb using the force plate. Force-plate analysis of walking animals before and after treatment with either AHA or DHA indicated some normalization of joint loading. However, osteophyte scores for meniscectomized joints injected with AHA and DHA were higher after treatment than those of the corresponding saline-treated group. Although the gross cartilage damage was lower than in saline-treated controls for both the HA-treated groups, the histological scores did not support this conclusion. Indeed, the tibial score for the DHA group was higher than for the AHA group (P < .05). These studies confirmed previous reports that meniscectomy of sheep stifle (knee) joints resulted in matrix changes similar to those described for early OA in humans. Both HA preparations appeared to improve gait, suggesting decreased lameness. Increased joint loading associated with gait improvement may account for the higher osteophyte scores in the treated groups. However, cartilage damage with DHA was found to be higher than when the lower-MW HA preparation (AHA) was used.

Animals↗

The effects of intraarticular administration of hyaluronan in a model of early osteoarthritis in sheep. II. Cartilage composition and proteoglycan metabolism.

A model of early osteoarthritis (OA) induced in ovine joints by medial meniscectomy was used to study the effects of two hyaluronan (HA) preparations (AHA and DHA) on cartilage composition and proteoglycan (PG) metabolism. DHA was an HA preparation with an average molecular weight (MW) of approximately 2.0 x 10(6) d, and AHA had an MW of approximately 8.0 x 10(5) d. Both preparations were administered intraarticularly once a week for 5 weeks starting 16 weeks after meniscectomy, and animals (n = 5) were killed 5 weeks after the last injection. Meniscectomized, saline-injected (n = 5) and nonoperated (n = 5) animals were used for controls. At necropsy, 3-mm-diameter full-depth cartilage plugs were sampled under sterile conditions from specific locations on the medial and lateral femoral condyles, tibial plateaus, patella, and trochlear groove. The cartilage plugs were cultured in Hams-F12 medium supplemented with 10% fetal calf serum for 24 hours, then for a further 48 hours in the presence of H2(35)SO4 to determine the biosynthesis of PGs. The percentage of 35S-PGs and sulfated glycosaminoglycans released into the media was also ascertained. The cartilage adjacent to the plugs was analyzed for collagen and proteoglycan content and differential extractability with guanidine hydrochloride (GuHCl) solutions. The extractability of PGs with 0.4 mol/L GuHCl (nondissociative conditions) was lower from the medial femoral cartilages of the DHA-treated group than from the corresponding saline-treated group. In contrast, the release of 35S-PGs from the tibial cartilages of the DHA-treated animals was higher than in the saline-treated group. The biosynthesis of 35S-PGs, determined in vitro, for cartilage derived from the medial compartment was generally lower than for the lateral regions of the meniscectomized joints. The biosynthetic activity was further reduced in joints injected with the two HA preparations, but DHA reduced 35SO4 incorporation into PGs more than AHA. It was concluded that reduced biosynthesis of 35S-PGs and secretion into media was a consequence of increased loading of joints in the HA-treated animals rather than a direct effect of these preparations on chondrocyte metabolism.

Animals↗

Flunarizine blocks elevation of free cytosolic calcium in synaptosomes following sustained depolarization.

Gerbil cerebral cortical synaptosomes loaded with the fluorescent calcium probe FURA-2 were used to study depolarization-induced presynaptic cytosolic free calcium concentration, as an in vitro model of cerebral ischemia. The depolarization-induced increase in intrasynaptosomal cytosolic free calcium concentration is not sodium-dependent or sodium channel-dependent and may be due to an influx of extrasynaptosomal calcium resulting from a cadmium- and omega-conotoxin-sensitive, nickel-, nifedipine-, and nimodipine-insensitive voltage-regulated channel. The depolarization-induced increase in intrasynaptosomal free cytosolic calcium concentration is also inhibited by flunarizine, a calcium antagonist that has protective effects in animal models of cerebral anoxia and ischemia. Our results suggest that presynaptic calcium uptake following depolarization may be mediated in part by an N-type channel. Flunarizine may block presynaptic calcium accumulation, in part, by blocking this N-type channel; this blockade may be just one of several mechanisms by which flunarizine exerts protective effects following cerebral ischemia.

Animals↗

Genetic infection induces protective in vivo immune responses.

Drug-induced abortive retroviral infection has been reported to induce both T-cell and B-cell immunity in vivo. We sought to analyze if replication-incompetent retroviruses could induce the development of similarly protective in vivo immune responses in a more desirable fashion. To evaluate retroviral transduction vaccination (genetic infection), a plasmid encoding human CD4 in a retroviral vector was transfected into the pA317 amphotropic retroviral packaging system. The resulting replication defective retrovirus was used to transduce BALB/c mice prior to tumor challenge with human CD4. Immunization elicited specific humoral and cellular anti-human CD4 responses. We evaluated anti-cell responses using a tumor model system. We observed that BALB/c mice challenged with SP2/0 lymphoma cells develop lethal tumors and die within 7 weeks of challenge. Cloned SP2/0 cells stably transfected with the human cell-surface antigen CD4 also develop tumors in naive mice and succumb to the tumors in a similar manner to SP2/0 inoculated animals. In contrast, CD4 retrovirus-transduced animals, when challenged with the CD4-expressing SP2/0 cells, demonstrated a low incidence of tumors and significantly enhanced survival compared to the mice immunized similarly with human CD8 retrovirus. These results establish an in vivo tumor challenge system with relevance to the development of protective in vivo immune responses, and indicate that genetic infection is a useful technique for inducing protective immunity.

Animals↗

Cooperative dimerization of paired class homeo domains on DNA.

Homeo domain-containing proteins mediate many transcriptional processes in eukaryotes. Because nearly all animal homeo proteins are believed to bind to short, highly related DNA sequences, the basis for their high specificity of action is not understood. We show that cooperative dimerization on palindromic DNA sequences can provide increased specificity to one of the three major classes of homeo domains, the Paired/Pax class. The 60-amino-acid homeo domains from this class contain sufficient information to bind cooperatively as homo- and heterodimers to palindromic DNA sequences; that is, the binding of one homeo domain molecule can increase the affinity of a second molecule by up to 300-fold. Different members of the Paired (Prd) class of homeo domains prefer different spacings between half-sites, as determined by the ninth amino acid residue of the recognition helix. In addition, this residue determines the identity of the base pairs at the center of the palindromic sites, as well as the magnitude of the cooperative interaction. The cooperative dimerization of homeo domains in the Prd class distinguishes them from other classes, whereas binding-site configuration and sequence specificity allow for distinctions within this class.

Animals↗

Annexin-1 localization in human skin: possible association with cytoskeletal elements in keratinocytes of the stratum spinosum.

Annexin-1 (also called lipocortin-1 or p35), a putative substrate of the epidermal growth factor/receptor kinase, protein kinase C, and transglutaminase, was immunolocalized in embryonic, neonatal, adult, and diseased human epidermis. In embryonic skin intense annexin-1 immunoreactivity was found in the periderm at 54 d estimated gestational age (EGA). Later (EGA = 91-143 d), annexin-1 immunoreactivity was restricted to basal keratinocytes. In neonatal skin, basal cells were often more heavily stained than were suprabasal keratinocytes, which were also stained. Only basal keratinocytes stained in adult plantar skin, but in thin skin annexin-1 was present in the basal, suprabasal, and sometimes even in the granular layers of the epidermis. Often, annexin-1 appeared concentrated around the perimeter of cells, especially tonofilament/desmosome-rich keratinocytes of the spinous-cell layer. At high magnification, annexin-1 appeared associated with distinct structures and was very granular in appearance in the intensely stained ductal keratinocytes of eccrine sweat glands, cells that are very highly enriched in keratin tonofilaments. This striking distribution in certain keratinocytes enriched in tonofilaments suggests a role for annexin-1 in cytoskeletal functions.

Adult↗

Isolation of a new marker and conserved sequences close to the DiGeorge syndrome marker HP500 (D22S134).

End fragment cloning from a YAC at the D22S134 locus allowed the isolation of a new probe HD7k. This marker detects hemizygosity in two patients previously shown to be dizygous for D22S134. This positions the distal deletion breakpoint in these patients to the sequences within the YAC, and confirms that HD7k is proximal to D22S134. In a search for coding sequences within the region commonly deleted in DGS we have identified a conserved sequence at D22S134. Although no cDNAs have yet been isolated, genomic sequencing shows a short open reading frame with weak similarity to collagen proteins.

Amino Acid Sequence↗

Conotruncal anomaly face syndrome is associated with a deletion within chromosome 22q11.

The conotruncal anomaly face syndrome was described in a Japanese publication in 1976 and comprises dysmorphic facial appearance and outflow tract defects of the heart. The authors subsequently noted similarities to Shprintzen syndrome and DiGeorge syndrome. Chromosome analysis in five cases did not show a deletion at high resolution, but fluorescent in situ hybridisation using probe DO832 showed a deletion within chromosome 22q11 in all cases.

Abnormalities, Multiple↗

Modulation of retinoblastoma cell characteristics by hexamethylene bis-acetamide and other differentiating agents in culture.

The undifferentiated Y-79 retinoblastoma cell line can be induced by specific agents to express characteristics of mature retinal cells. In the present study, attached Y-79 cell cultures were treated with hexamethylene bis-acetamide (HMBA) and other differentiating agents and examined for "neuronal" and other properties. Immunocytochemical staining was performed with antibodies against neuron- and retina-specific antigens, [synaptophysin, interphotoreceptor retinoid-binding protein (IRBP), neural cell adhesion molecule (N-CAM), and rod- and cone-specific transducin (TR alpha and TC alpha)] and microtubule-associated protein (MAP-1) and tubulin. Enhanced expression of tubulin was observed with cAMP treatment in FBS media. Expression of N-CAM was observed in all groups. Morphological differentiation was pronounced with HMBA and butyrate treatment, with HMBA inducing increased tubulin expression after 2 weeks of treatment. Expression of TR alpha was minimal under all culture conditions, whereas TC alpha was ubiquitously expressed. This supports the concept that Y-79 retinoblastoma is predominantly of cone neuronal origin and that, surprisingly, immunocytochemical differentiation is not correlated with the marked morphological changes induced by the major differentiating agents used.

Acetamides↗

Comparison of clinical responses to natural and synthetic surfactants.

The clinical responses to both natural and synthetic surfactants were observed in two District General Hospital Neonatal Units who were centrally randomised as part of two separate multicentre trials (OSIRIS and Curosurf 4). Forty five infants were enrolled consecutively in the OSIRIS trial using synthetic surfactant (Exosurf), while 21 infants were subsequently enrolled in the Curosurf 4 trial using natural surfactant (Curosurf). There were no significant differences between the groups for mean birth weight, gestational age, inspired oxygen (FiO2), or arterial: alveolar oxygen ratio (a/A) prior to surfactant administration. Oxygen requirements fell significantly more rapidly within the first 24 hours for patients treated with Curosurf compared to Exosurf (p < 0.001). Mean duration of > 40% oxygen requirement was significantly shorter in the Curosurf group (2.6 days) compared to 8.0 days in the Exosurf group (p < 0.01). Mean duration of oxygen therapy was also significantly shorter in the Curosurf group (10.2 days) compared to 17.1 days in the Exosurf group (p < 0.05). Ten infants (24%) in the Exosurf group developed intraventricular haemorrhage (IVH) compared to none in the Curosurf group (p < 0.05). As oxygen requirements appear to decrease more rapidly following administration of Curosurf compared to Exosurf a large prospective randomized multicentre trial needs to be performed to compare the effects of these surfactants on both short and long-term outcome.

Arteries↗

Magnetic resonance imaging and morphometric quantitation of cartilage histology after chronic infusion of interleukin 1 in rabbit knees.

Cartilage pathology in rabbit knees was monitored by noninvasive magnetic resonance imaging (MRI) and evaluated using morphometric histologic measurements. Infusion of rabbit knees with the cytokine interleukin 1 induces cartilage degradation and inflammation. A miniosmotic pump was implanted subcutaneously to deliver interleukin 1 through a polyethylene catheter inserted into the rabbit knee. Rabbit knees were imaged using MRI and prepared for histologic examination at 5 and 12 days after chronic infusion of interleukin 1. MRI obtained 0.7-mm sections for three-dimensional reconstruction of cartilage image. Cartilage deterioration near the site of infusion was visible on MRI. MRI measurements indicated a reduction in cartilage thickness. Histology revealed a loss of staining of cartilage matrix proteoglycan, synovial hypertrophy, and perichondral bone resorption. Morphometric analysis of cartilage histology indicated a reduction in both cellularity (chondrocytes/m mu 2 area) and cell to matrix area ratio. These observations suggest that a loss of proteoglycan, an early event in cartilage degeneration, can be detected by MRI.

Animals↗

A South African outpatient drug treatment centre.

The Cape Town Drug Counselling Centre is an outpatient drug treatment service which has been operational since 1985. Statistics obtained from 1990 are detailed, describing patient characteristics in respect of referral sources, age, sex, occupational status, educational level and drugs abused. The typical client profile that emerges is of a young employed male of limited education, referred from a non-professional source, who smokes cannabis alone or with methaqualone (Mandrax). Management of clients, which includes psychotherapy with an emphasis on group-work and medical intervention, is described, and proposed areas for further research are outlined.

Adolescent↗