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Biomedical subjects

D M Dawson

Publications and source records attributed to D M Dawson.

At least 19 recordsLinked to original sources
PubMed1998

Altered expression of RET proto-oncogene product in prostatic intraepithelial neoplasia and prostate cancer.

BACKGROUND: The RET proto-oncogene encodes a protein that belongs to the tyrosine kinase growth factor receptor family. Germline point mutations in RET are found in individuals with multiple endocrine neoplasia (MEN) syndromes, and gene rearrangements have been reported in papillary thyroid cancers. We recently identified transcripts of the RET proto-oncogene in human prostate cancer xenografts and prostate cancer cell lines by means of reverse transcription-polymerase chain reaction analyses. The purpose of this study was to investigate Ret protein expression in human prostate tissue. METHODS: Ret protein expression was evaluated immunohistochemically in formalin-fixed, paraffin-embedded whole-prostate sections. The prostate specimens were obtained from 30 patients with prostate cancer after radical prostatectomies. Ret protein expression was compared in tumor foci and benign prostatic tissue. Medullary thyroid carcinoma tissue associated with an MEN syndrome and papillary thyroid cancer tissue served as positive controls. RESULTS: Ret appeared to be overexpressed in high-grade (histopathologically advanced) prostatic intraepithelial neoplasia (PIN) and prostate cancer when compared with its expression level in benign prostatic secretory epithelium. In addition, there was an apparent increase in Ret protein expression with decreased cellular differentiation, i.e., increasing Gleason pattern. CONCLUSION: Expression of the RET proto-oncogene in benign prostatic epithelium, high-grade PIN, and histopathologically advanced prostate cancer suggests that RET may play a role in the growth of both benign and neoplastic prostate epithelial cells.

Drosophila Proteins↗
PubMed1997

Hereditary ataxia with sensory neuronopathy: Biemond's ataxia.

We report the case of a man with late-onset hereditary ataxia and sensory loss. Three of his sisters were affected by a similar disorder; to date no other members of his family have developed symptoms. The clinical features of this family are similar to a rare form of autosomal dominant hereditary ataxia, recently classified as SCA4. Postmortem findings indicate that this syndrome is marked by degeneration of cerebellar Purkinje cells, dorsal root sensory ganglion neurons, and the ascending posterior columns. Similar clinical and pathologic findings were reported by Biemond in 1954.

Adult↗
PubMed1997

Fibrin deposition in Peyronie's disease plaque.

PURPOSE: Peyronie's disease is a pathological fibrosis characterized by excessive deposition of collagen in the plaque. Although the etiology of Peyronie's disease is unknown, trauma has been hypothesized as the inciting event. In an effort to obtain more insight into the pathogenesis of Peyronie's disease plaque tissue was examined for collagen, elastic fiber, and fibrin content and distribution. MATERIALS AND METHODS: Plaque tissue specimens from 33 patients with Peyronie's disease, control penile tissue and nodular tissue from 8 patients with Dupuytren's contracture were analyzed histochemically for collagen staining and elastic fiber structure and distribution. Plaque tissue from 19 Peyronie's disease patients, control tissue and nodular tissue from Dupuytren's disease were also analyzed for the presence of fibrin by histochemical staining and immunoblotting. RESULTS: Aberrantly stained collagen was detected in 32 of 33 plaque specimens (97%) and disrupted elastic fibers in 31 of the same specimens (94%). Fibrin deposition was detected histochemically in plaque tissue from 18 of 19 patients (95%) but it was not detectable in normal or scarred tunica from control patients. The presence of authentic fibrin accumulation in plaque tissue was confirmed by immunoblot analysis but fibrin was not detected in dermal tissue extracts from the same patient. Aberrant collagen staining and fibrin deposition were detected in nodular tissue from 7 of 8 Dupuytren's contracture patients (88%) and altered elastic fibers in 5 of the same patients (63%). CONCLUSIONS: Deposition of fibrin in plaque tissue is consistent with the hypothesis that repetitive microvascular injury results in fibrin deposition in the tissue space and has served to provide insights into the pathophysiology of Peyronie's disease. We propose a model that accounts for the clinical and biological features of Peyronie's disease.

Adult↗
PubMed1996

A familial factor independent of CAG repeat length influences age at onset of Machado-Joseph disease.

Machado-Joseph disease (MJD) is a late-onset, progressive, neurodegenerative disorder caused by the expansion of an unstable trinucleotide (CAG) repeat sequence in a novel gene (MJD1) on chromosome 14. Previous studies showed that age at onset is negatively correlated with the number of CAG repeat units, but only part of the variation in onset age is explained by CAG repeat length. Ages at onset and CAG repeat lengths of 136 MJD patients from 23 kindreds of Portuguese descent were analyzed, to determine whether familial factors independent of CAG repeat length modulate age at onset of MJD. Correlation among sibs for onset age adjusted for CAG repeat length was .43, which indicates that an environmental or genetic factor common to sibs influences onset age. Positive correlations were also observed for avuncular (r = .22) and first-cousin pairs (r = .28), which supports the hypothesis that a genetic factor is influencing age at onset. Commingling analysis of onset ages adjusted for CAG repeat length identified three distributions in this population of affected individuals. Further studies of a much larger sample are needed to determine whether these distributions represent the influence of a genetic or environmental factor.

Adolescent↗
PubMed1995

Entrapment neuropathies: clinical overview.

Causes include congenital defects, trauma, and inflammation. Some forms are overdiagnosed, particularly carpal tunnel syndrome. Others--such as thoracic outlet syndrome and anterior interosseous nerve syndrome--are rare. Diagnosis and management are relatively straightforward in most cases, but much remains to be learned about the natural course and prevention of these disorders.

Carpal Tunnel Syndrome↗
PubMed1995

Correlation between CAG repeat length and clinical features in Machado-Joseph disease.

Machado-Joseph disease (MJD) is associated with the expansion of a CAG trinucleotide repeat in a novel gene on 14q32.1. We confirmed the presence of this expansion in 156 MJD patients from 33 families of different geographic origins: 15 Portuguese Azorean, 2 Brazilian, and 16 North American of Portuguese Azorean descent. Normal chromosomes contain between 12 and 37 CAG repeats in the MJD gene, whereas MJD gene carriers have alleles within the expanded range of 62-84 CAG units. The distribution of expanded alleles and the gap between normal and expanded allele sizes is either inconsistent with a premutation hypothesis or most (if not all) of the alleles we studied descend from a common ancestor. There is a strong correlation between the expanded repeat size and the age at onset of the disease as well as the clinical presentation. There is mild instability of the CAG tract length with transmission of the expanded alleles; both increase and decrease in size between parents and progeny occur, with larger variations in male than in female transmissions. Together, these effects can partly explain the variability of age at onset and of phenotypic features in MJD; however, other modifying factors must exist.

Adult↗
PubMed1995

Therapy for multiple sclerosis.

Multiple sclerosis is hypothesized to be a cell-mediated autoimmune disease directed against central nervous system myelin. Immunotherapy is directed at decreasing the autoimmune response using both specific and nonspecific modulation of the immune system in an attempt to halt accumulation of disability. Symptomatic therapy may also help multiple sclerosis patients.

Humans↗
PubMed1993

Entrapment neuropathies of the upper extremities.

The three syndromes described in this article were chosen from about a dozen nerve-compression disorders that affect the arm from scapula to digits. They illustrate the range of problems encountered. None of the other syndromes are as common, and in some instances (pronator syndrome and anterior interosseous syndrome), localized inflammation is at least as common a cause of neuropathy as is compression. Some syndromes of nerve compression have important implications for musicians, athletes, and those who place stress on the upper limbs through heavy or repeated use. Well-designed prospective trials are clearly needed to expand our knowledge of the prevention and treatment of the entrapment neuropathies. Much more needs to be known about the long-term natural history of these disorders, since prevention is usually possible.

Arm↗
PubMed1993

Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis.

Multiple sclerosis (MS) is thought to be an autoimmune disease mediated by T lymphocytes that recognize myelin components of the central nervous system. In a 1-year double-blind study, 30 individuals with relapsing-remitting MS received daily capsules of bovine myelin or a control protein to determine the effect of oral tolerization to myelin antigens on the disease. Six of 15 individuals in the myelin-treated group had at least one major exacerbation; 12 or 15 had an attack in the control group. T cells reactive with myelin basic protein were reduced in the myelin-treated group. No toxicity or side effects were noted. Although conclusions about efficacy cannot be drawn from these data, they open an area of investigation for MS and other autoimmune diseases.

Adult↗
PubMed1993

Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group.

Previous studies reported that a 2- to 3-week course of IV cyclophosphamide plus adrenocorticotropic hormone (ACTH) induction can temporarily halt progressive MS for a period of 12 months in the majority of patients treated, after which reprogression occurs. The Northeast Cooperative Multiple Sclerosis Treatment Group was formed to determine whether outpatient pulse cyclophosphamide therapy could affect reprogression and whether there were differences between a modified induction regimen and the previously published regimen. Two hundred fifty-six progressive MS patients were randomized into four groups to receive IV cyclophosphamide/ACTH via the previously published versus a modified induction regimen, with or without outpatient IV cyclophosphamide boosters (700 mg/m2 every other month for 2 years). There were blinded evaluations performed every 6 months. Results demonstrate that (1) there were no differences between the modified and the published induction regimens either in terms of initial stabilization or subsequent progression; (2) without boosters, the majority of patients continued to progress; and (3) in patients receiving boosters, there was a statistically significant benefit at 24 months and 30 months (p = 0.04). Time to treatment failure after 1 year was also significantly prolonged in the booster versus the nonbooster group (p = 0.03). Age was the most important variable that correlated with response to therapy in that amelioration of disease progression occurred primarily in patients 40 years of age or younger. Boosters had a significant benefit on time to treatment failure in patients ages 18 to 40, p = 0.003, but not in patients ages 41 to 55, p = 0.97.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Machado-Joseph disease in New England: clinical description and distinction from the olivopontocerebellar atrophies.

Experience is described in 25 patients from southern New England with Machado-Joseph Disease, examined serially at annual screening clinics. The disorder is dominantly inherited, with a wide range of phenotypic variation. Core clinical features described include ataxia, nystagmus, dysarthria, facial fasciculations, and lid retraction, producing a characteristic staring expression. In addition, young onset patients have spasticity, extrapyramidal rigidity, and dystonic manifestations. Late onset patients often have distal atrophy and sensory loss. Postural instability is often an early feature. We discuss the distinction of this entity from the olivopontocerebellar atrophies.

Adolescent↗
PubMed1992

Lower motor neuron dysfunction in patients with multiple sclerosis.

A patient in whom multiple sclerosis (MS) was ultimately diagnosed presented with a lower motor neuron syndrome involving 1 hand, with EMG evidence of denervation. Twelve other patients were subsequently identified with definite MS and asymmetric hand atrophy. These patients were studied clinically and electrophysiologically. Evidence of chronic and ongoing denervation was noted in the hands of 12 of the 13 patients; in only 3 patients could the EMG abnormalities be accounted for by peripheral nerve lesions. Thus, lesions resulting in lower motor neuron damage may occur in the central nervous system in MS patients. We suggest that demyelination in the region of the ventral root exit zone may account for these findings.

Action Potentials↗
PubMed1992

Bubble hair.

An unusual hair dystrophy was studied by means of light and electron microscopy. Hair fibers demonstrated a boomerang deformity containing small and large "bubbles". Electron microscopy revealed a loss of cortical cells and medulla at these sites. Cross-section images showed either a single large cavity or a reticulated, "swiss cheese-like" loss of cells. These two cases represent the second and third reported cases of bubble hair deformity. We present the second light and electron microscopic study of this disorder, including new electron microscopic findings. The cause of bubble hair deformity remains obscure. The involved tufts of wiry hair resolved with gentle hair care. This suggests that trauma to the hair shaft may play a role. It is likely that additional cases of bubble hair remain unrecognized. Investigation of other patients with localized tufts of wiry hair is likely to reveal additional cases.

Adult↗
PubMed1991

Neuralgic amyotrophy in association with radiation therapy for Hodgkin's disease.

We describe 4 patients with Hodgkin's disease who developed neuralgic amyotrophy in the setting of radiation therapy. In contrast to tumor progression or radiation plexopathy, the symptom onset was abrupt and occurred within days to weeks of receiving radiation treatments. There is an association between Hodgkin's disease, radiation therapy, and neuralgic amyotrophy.

Adult↗
PubMed1991

Acute nontraumatic myelopathies.

Acute myelopathies (acute transverse myelopathies) can be divided into two major groups. Vascular myelopathies are caused by aortic disease, surgery, or intrinsic vascular disease of cord vessels. Inflammatory/demyelinative myelopathies include lupus erythematosus, various viral infections, and primary demyelinating disease. Criteria for diagnostic decisions and recent data from magnetic resonance imaging are reviewed.

Acute Disease↗
PubMed1990

The use of sensory action potentials in the diagnosis of peripheral nerve disease.

We review the different measurements that can be derived from recordings of compound sensory action potentials, and describe how less commonly measured aspects may be of use in clinical situations. In addition to the frequently obtained maximum conduction velocity and amplitude, minimum conduction velocity may be measured if near nerve electrodes and response averaging are used. Minimum conduction velocity is a sensitive measure of both axonal and demyelinating peripheral nerve pathology. Activity-dependent conduction is another aspect of sensory conduction that may provide additional information for the clinician. Refractory period of transmission has been used to diagnose subtle demyelinating lesions, as well as some axonal disorders. Supernormal period and the conduction of trains of stimuli may also be useful, although, at present, they remain predominantly research tools.

Action Potentials↗
PubMed1989

Perioperative nerve lesions.

The scenario is all too familiar. A patient has a surgical procedure. Anesthesia is uneventful and the procedure goes well. Nothing untoward is observed in the recovery room. Later that evening the patient complains of numbness, weakness, or pain, and a neurological deficit is found. A neurologist is called, examines the patient, and it is concluded that a nerve lesion has occurred, because of stretch, ischemia, compression, or laceration. A subsequent electromyogram and nerve conduction study confirm the clinical impression, but offer little in the way of explanation. Over the subsequent months, the patient makes a slow recovery but there has been a prolonged period of pain and disability. Liability issues loom. This scenario could reflect a number of different nerve lesions. This review illustrates the different modes of pathogenesis that may occur and the variable nature of the neurological deficits. We grouped these lesions according to the clinical setting in which they occur.

Brachial Plexus↗