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Biomedical subjects

J C Steele

Publications and source records attributed to J C Steele.

At least 37 records · Page 2Linked to original sources
PubMed1997

Familial nature and continuing morbidity of the amyotrophic lateral sclerosis-parkinsonism dementia complex of Guam.

Chamorros suffer from two neurologic syndromes known as ALS and the parkinsonism-dementia complex (PDC) of Guam. We report mortality figures for these syndromes during 1991 to 1995 and compare them with those at 5-year intervals dating back to 1951. In contrast to predictions of disease disappearance, both syndromes remain prevalent. However, age of onset and age at death have increased for both syndromes, suggesting that shifting environmental factors are causing disease postponement. We also report the clinical, familial, neuropathologic, and immunohistochemical findings on a consecutive autopsy series of Guamanian Chamorro cases. Twelve cases were diagnosed as PDC, known locally as "bodig," and three as ALS, known locally as "lytico." All but three of these fifteen patients had a pronounced family history of similar illness. Eight of twelve boding patients had siblings who were also affected with bodig; two of three lytico cases had siblings afflicted with lytico. The family histories are compatible with genetic transmission of each syndrome. The neuropathology of bodig is characterized by severe and widespread neurofibrillary tangle (NFT) development. NFTs are surrounded by reactive microglia and reactive astrocytes, and complement proteins and other molecules connected with inflammation are associated with them. Similar inflammatory responses also occur in Alzheimer's disease (AD) but have been largely attributed to the presence of senile plaques. These data indicate that tangles, as well as plaques, generate inflammatory reactions that such reactions may exacerbate the fundamental pathology in bodig as well as in AD.

Aged↗
PubMed1996

Midkine-like immunoreactivity in extracellular neurofibrillary tangles in brains of patients with parkinsonism-dementia complex of Guam.

Midkine (MK) has been shown to be present in amyloid deposits in Alzheimer's disease (AD). In the present study, expression of midkine was examined immunohistochemically in brains of patients with the parkinsonism-dementia complex of Guam, lytico bodig disease (LB), using an affinity purified antibody to midkine. Positive staining was identified on some extracellular neurofibrillary tangles. The relative prevalence was somewhat less than for beta-amyloid protein (Abeta)-positive extracellular tangles. The results demonstrate that expression of MK and Abeta is not an exclusive feature of amyloid deposits in Alzheimer brain, but is also found in LB brain.

Antibody Specificity↗
PubMed1996

Neurofibrillary tangles of Guam parkinson-dementia are associated with reactive microglia and complement proteins.

Guamanian parkinsonism-dementia, locally described as bodig, is characterized by the widespread appearance of neurofibrillary tangles in cortical and subcortical areas. These tangles have similar regional distribution and immunohistochemical profile to those found in Alzheimer disease (AD). We studied the immunohistochemical staining of these tangles, as well as those of AD, using antibodies to complement proteins and related molecules. In bodig, as in AD, extracellular tangles were intensely decorated with antibodies to C1q, C4d and C3d, but not fraction Bb of factor B, properidin or immunoglobulins. This is evidence that the classical, but not the alternative complement pathway is activated on extracellular tangles and that the activation is independent of antibodies. Immunohistochemical staining for amyloid P, an in vitro activator of complement, was remarkably similar to that for the C1q, C4d and C3d in both bodig and AD. This was not the case for beta-amyloid protein (BAP), another in vitro complement activator. Positive staining was observed in only a minority of extracellular tangles in bodig and was only rarely observed in those of AD. BAP would therefore not appear to be a candidate for activating complement on extracellular neurofibrillary tangles. Reactive microglia and reactive astrocytes were closely associated with complement positive extracellular neurofibrillary tangles, indicating an inflammatory response similar to that seen in AD.

Adult↗
PubMed1996

Distinct distribution of apolipoprotein E and beta-amyloid immunoreactivity in the hippocampus of Parkinson dementia complex of Guam.

The distribution of apolipoprotein E (ApoE) was studied in the brain tissue of cases of the amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam, locally known as lytico bodig disease (LB), and compared with cases of Alzheimer's disease (AD) and normal brain tissue. In both LB and AD, strong ApoE immunostaining was observed in association with pathological lesions. In LB, these were mainly extracellular neurofibrillary tangles (eNFTs) which were intensely immuno-positive for ApoE. Occasional diffuse beta-amyloid protein (beta AP) deposits appear in this disorder and they were moderately immunopositive. In AD, senile plaques and diffuse beta AP deposits were intensely immunopositive, while eNFTs were only moderately immunopositive. The reason for the strong association of ApoE with the pathological entities in LB and AD is unknown, but may be related to a scavenger function which does not involve lipid metabolism. In both LB and AD, subpial and layer I diffuse deposits were ApoE negative but beta AP positive. Intracellular NFTs were mostly ApoE negative. A few showed weak positive staining. These data suggest that ApoE appears in LB and AD pathological lesions only after they are well established. In all controls, as well as all LB and AD cases, strong ApoE immunoreactivity was observed in unidentifiable structures in capillaries. Weak staining in a few neurons and very weak staining of an occasional astrocyte was observed. The source of ApoE which is deposited on extracellular pathological structures in LB and AD is unknown.

Adult↗
PubMed1995

Relationship of amyloid beta/A4 protein to the neurofibrillary tangles in Guamanian parkinsonism-dementia.

The Chamorro population of the island of Guam is highly susceptible to a disease called lytico-bodig (LB), which clinically resembles a mixture of amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer disease (AD). The disease is characterized by the widespread development of neurofibrillary tangles in the central nervous system. These tangles have an immunohistochemical profile indistinguishable from that seen in AD. We studied by immunohistochemistry the occurrence of intracellular and extracellular neurofibrillary tangles in LB in the entorhinal cortex, hippocampus and substantia nigra using antibodies to tau protein and ubiquitin. We also studied the relationship of these tangles to amyloid precursor protein (APP) and its beta-amyloid fragment (BAP), using multiple antibodies to BAP and other APP sequences. In advanced cases of LB, the development of neurofibrillary tangles was far more severe than in advanced cases of AD. Virtually all neurons of CA-1 and the subiculum were lost and only ghost tangles remained. In areas dominated by such extracellular tangles, BAP deposits were frequently observed developing around the fibers of ghost tangles. In some cases, the deposits covered only a few of the fibers, but in others, they seemed to envelope the complete tangle. The deposits were thioflavin S and Congo red positive, indicating that the BAP was in a consolidated form. We describe these entities as "tangle-associated amyloid deposits". Such BAP deposits have previously been described in some cases of AD, dementia pugilistica and LB. However, we found them in all cases of LB with dementia in the hippocampal-entorhinal areas and in most cases in the substantia nigra. They do not evolve from diffuse BAP deposits since they are remote from them, and they do not trap dystrophic neurites. The fact that extracellular tangle material can act as a nidus for BAP build-up in LB suggests that further consideration needs to be given to the ways in which extracellular BAP deposits are formed.

Adult↗
PubMed1994

Amyotrophic lateral sclerosis and parkinsonism-dementia from Guam: differences in neurofibrillary tangle distribution and density in the hippocampal formation and neocortex.

Amyotrophic lateral sclerosis/parkinsonism-dementia complex is a highly prevalent neurodegenerative disorder among the native Chamorro population of Guam, and is characterized by widespread formation of neurofibrillary tangles. In the present study, the distribution of neurofibrillary tangles was quantitatively assessed in the cerebral cortex of cases presenting with either predominant amyotrophic lateral sclerosis or parkinsonism-dementia symptomatology. Results show that although the regional and laminar lesion distribution is qualitatively similar in both groups, cases with predominant parkinsonism-dementia generally have higher lesion densities than cases with amyotrophic lateral sclerosis. Interestingly, layer II of the entorhinal cortex was affected to the same degree in both conditions. In both groups, the CA1 field of the hippocampus, subiculum, and entorhinal cortex were the most affected areas. In the neocortex, the perirhinal and inferior temporal cortex consistently had higher lesion densities than the frontal, parietal, and cingulate cortex, whereas the visual cortex was practically devoid of lesions. Also, most of the neurofibrillary tangles were located in the supragranular layers of the neocortex, with relatively low densities in the infragranular layers, in both brain groups. Interestingly, the primary motor cortex contained more neurofibrillary tangles in parkinsonism-dementia than in amyotrophic lateral sclerosis cases. It is possible that the differences in regional neurofibrillary tangle densities reflect the variable severity of the dementing process observed between the two groups of patients. Several studies on Alzheimer's disease and related disorders indicate that the regional and laminar cortical localization of neurofibrillary tangles may parallel the degeneration of specific corticocortical projections. The present data suggest that the population of corticocortical projections involved in Guamanian cases differs substantially from that affected in Alzheimer's disease. The differential distribution and densities of the lesions may contribute to the differences in symptomatology and severity of dementia among Alzheimer's disease and Guamanian cases, although these neurodegenerative disorders as well as related illnesses may share certain etiopathogenetic mechanisms.

Adult↗
PubMed1994

Amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam: quantitative neuropathology, immunohistochemical analysis of neuronal vulnerability, and comparison with related neurodegenerative disorders.

Amyotrophic lateral sclerosis/parkinsonism-dementia complex (lytico-bodig) is a chronic neurodegenerative disorder with high prevalence among the native Chamorro population of Guam. Neuropathological, biochemical, and immunohistochemical analyses were performed on a relatively large series of Guamanian cases and compared to Alzheimer's disease cases. Thioflavin S and antibodies to amyloid beta A4 and tau proteins were used for analysis of pathological changes, and antibodies to the calcium-binding proteins parvalbumin and calretinin, and to a nonphosphorylated epitope on neurofilament protein to study select neuronal populations. A differential distribution of neurofibrillary tangles was observed in the neocortex of Guamanian cases compared to Alzheimer's disease cases, with much higher lesion counts in supragranular than in infragranular layers. Also, Guamanian cases with predominant parkinsonism had generally higher neurofibrillary tangle densities than cases with predominant amyotrophic lateral sclerosis. In addition, there was a certain degree of heterogeneity, qualitatively and quantitatively, in the biochemical distribution of tau proteins among Guamanian and Alzheimer's disease cases as revealed by Western blot analysis. Previous studies have suggested that the clinical symptomatology observed in patients suffering from Alzheimer's disease is related to the dramatic loss of specific corticocortically projecting neurons in the neocortex. Interestingly, a subset of neurofilament-rich pyramidal neurons known to be dramatically affected in Alzheimer's disease appears to be resistant in lytico-bodig. Finally, as in Alzheimer's disease, calcium-binding protein-containing interneurons are not affected. These data suggest that the set of projection neurons affected in Guamanian cases may not correspond to those involved in Alzheimer's disease, and that both disorders are characterized by specific patterns of neuronal vulnerability.

Adult↗
PubMed1994

Progressive supranuclear palsy. Historical notes.

Progressive supranuclear palsy (PSP) is the name Dr. J. Clifford Richardson chose to designate an unusual clinical syndrome he first identified in the 1950s. Neurofibrillary degeneration is the hallmark of this fatal brain disease, and during our study of Richardson's patients, Professor Jerzy Olszewski and I also observed granulovacuolar degeneration, and widespread nerve cell loss and gliosis in subcortical and brain stem nuclei. The histopathological features bear a striking resemblance to those seen in postencephalitic parkinsonism after von Economo's epidemic encephalitis, and in the parkinsonism-dementia complex of Guam (PDC). During the past 30 years, neurologists confirm that progressive supranuclear palsy is a universal, sporadic and not uncommon neurodegeneration of middle and late life. Many fine studies, as reported here, have advanced our understanding of PSP but its cause, and thereby its cure, is still to be revealed. These historical notes tell of our observations from 1955 to 1975. We are pleased that colleagues remember these early descriptions and honor us by calling this disease, the Steele-Richardson-Olszewski (SRO) syndrome.

Canada↗
PubMed1993

Pathologic findings in the retinal pigment epitheliopathy associated with the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam.

BACKGROUND: A pigment epitheliopathy that resembles ophthalmomyiasis interna occurs in approximately 10% of a large sample of the Chamorro population of Guam age 39 years or older; the rate is approximately 50% among those who have amyotrophic lateral sclerosis or Parkinsonism-dementia complex (lytico bodig). METHODS: Since publication of an earlier clinical report of affected patients, several of them have died of their neurologic disease, and their eyes were obtained for pathologic study. This is the first pathologic report of the retinal pigment epitheliopathy seen in the setting of amyotrophic lateral sclerosis/Parkinsonism-dementia complex of Guam and is based on examination of 13 eyes from 7 patients. RESULTS/CONCLUSION: Focal areas of attenuation of the retinal pigment epithelium in association with a reduced amount of intracellular pigment correlated with the funduscopic and gross appearance. No larvae were seen, and there was no evidence of inflammation. The pathogenesis of this pigment epitheliopathy remains undetermined.

Amyotrophic Lateral Sclerosis↗
PubMed1993

An unusual retinal pigment epitheliopathy endemic to the island of Guam.

An unusual retinal pigment epitheliopathy resembling ophthalmomyiasis interna posterior (OMI) is endemic to Guam. Sixteen percent of a sample of the indigenous population were found to have the retinopathy. Fifty-two percent of a group of individuals suffering from amyotrophic lateral sclerosis/Parkinsonism-dementia complex (ALS/PDC) were found to have the same retinopathy. Although the retinal appearance is similar to that caused by a subretinal parasite, a definite etiology has not been identified. Three case reports are presented as samples of the clinical presentation of the condition.

Adult↗
PubMed1993

Cross-cultural cognitive examination: validation of a dementia screening instrument for neuroepidemiological research.

OBJECTIVE: Validation of a new instrument for screening dementia, the Cross Cultural Cognitive Examination (CCCE), is described. DESIGN: Criterion and concurrent validation and cross-cultural comparison of a new instrument. PARTICIPANTS: All individuals over the age of 40 in a village in southern Guam participated in a door-to-door survey. Alzheimer's and Parkinson's Disease patients and healthy controls aged 40-90 participated in the US mainland study. MEASUREMENTS: The CCCE was administered to all subjects. Effects of age, language, education, and gender on test performances and social-cultural differences were assessed. Concurrent validation of the test with respect to other well accepted screening instruments was determined. RESULTS: High specificity (> 94%) and sensitivity (> 99%) for detecting dementia were found in Guam and US mainland samples, and these were not biased by differences in gender, linguistic preference, education, or cultural background. Sensitivity and specificity of the CCCE matched or exceeded that of already accepted dementia screening instruments. CONCLUSIONS: These validation studies support the usefulness of the CCCE for identifying patients with generalized dementia, rather than focal types of cognitive impairment, quickly and reliably in cross-cultural neuroepidemiological research.

Adult↗
PubMed1993

Production and characterization of human proliferative T-cell clones specific for human papillomavirus type 1 E4 protein.

Human papillomavirus type 1 (HPV1) virions and E4 protein purified from cutaneous warts were tested in lymphocyte proliferation assays using normal individuals. Both antigens were found to be capable of eliciting good lymphoproliferative responses. Several T-cell clones specific for wart E4 protein were obtained from a donor who had consistently responded very well to E4 in these initial assays. They were maintained in culture by repeated stimulation with antigen and interleukin-2, using an autologous mitomycin-treated lymphoblastoid cell line as a source of antigen-presenting cells. Two of these clones (3F5 and 4A8), which behaved identically, have been studied in more detail. A series of overlapping synthetic peptides covering the entire E1 E4 protein sequence was used to identify a single T-cell epitope which maps to a strongly hydrophilic region spanning amino acid residues 38 to 50. We have also tested the ability of a panel of major histocompatibility complex class II-matched and -mismatched lymphoblastoid cell lines to present this peptide to the T-cell clones in proliferation assays. The study reports that the epitope is restricted through HLA-DQ7 and that it can be recognized by T cells with different T-cell receptor gene rearrangements.

Amino Acid Sequence↗
PubMed1991

Odor identification deficit of the parkinsonism-dementia complex of Guam: equivalence to that of Alzheimer's and idiopathic Parkinson's disease.

Olfactory dysfunction is among the first signs of Alzheimer's disease (AD), idiopathic Parkinson's disease (PD), and the parkinsonism-dementia complex (PDC) of Guam. We have recently demonstrated that the odor identification and detection deficits of patients with PD are equivalent to those of patients with mild AD when subtle differences in cognitive function are statistically controlled for by analysis of covariance. In contrast, patients with progressive supranuclear palsy (PSP) and patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism evidence olfactory function much more similar to that of normal controls. In the present study, we administered the University of Pennsylvania Smell Identification Test and the Picture Identification Test to 24 patients with early signs of the PDC of Guam and statistically compared their test scores to those of 24 early-stage AD and 24 early-stage PD patients of similar age and gender from the United States mainland. Although the PDC group evidenced slightly more difficulty in identifying pictures than did the other 2 groups, the odor identification deficit associated with this disorder was of the same magnitude as that observed in AD and PD, suggesting that olfactory testing cannot be used to distinguish among these 3 diseases and that the olfactory dysfunction of these disorders may reflect a common neurologic substrate.

Adult↗
PubMed1991

Noninvasive detection of Chlamydia trachomatis urethritis in men by a rapid enzyme immunoassay test.

BACKGROUND: The purpose of this investigation was to evaluate the ability of a rapid enzyme immunoassay test to noninvasively detect Chlamydia trachomatis urethritis in men from a urine specimen. METHODS: Urethral samples and urine from 207 patients were evaluated. Urethral and urine sediment Gram stains, leukocyte esterase dipstick tests, and enzyme immunoassay analyses of centrifuged and uncentrifuged urine were compared with urethral C trachomatis culture. RESULTS: The prevalence of infection in this population was 10.3%. Sensitivity and specificity of the enzyme immunoassay on the centrifuged urine specimen were 70% and 96%, respectively. The positive and negative predictive values were 67% and 97%, respectively. The uncentrifuged urine enzyme immunoassay sensitivity was 35.7% and specificity was 98.9%. Leukocyte esterase test sensitivity compared with that of the Neisseria gonorrhoeae and/or C trachomatis cultures was 83.3%, and specificity was 52%. CONCLUSIONS: The rapid enzyme immunoassay clinically complemented the screening urine sediment Gram stain and the leukocyte esterase test. The judicious use of a noninvasive C trachomatis rapid enzyme immunoassay test to identify organism-specific urethritis may improve patient management of sexually transmitted disease.

Adult↗
PubMed1991

Olfactory dysfunction in three neurodegenerative diseases.

Olfactory dysfunction is among the first signs of Alzheimer's disease (AD), idiopathic Parkinson's disease (PD), and the parkinsonism-dementia complex (PDC) of Guam. We have recently demonstrated that the odor identification and detection deficits of patients with PD are equivalent to those of patients with mild AD when subtle differences in cognitive function are statistically controlled for by analysis of covariance. In contrast, patients with progressive supranuclear palsy (PSP) and patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism evidence olfactory function much more similar to that of normal controls. In the present study, we administered the University of Pennsylvania Smell Identification Test and the Picture Identification Test to 24 patients with early signs of the PDC of Guam and statistically compared their test scores to those of 24 early-stage AD and 24 early-stage PD patients of similar age and gender from the United States mainland. Although the PDC group evidenced slightly more difficulty in identifying pictures than did the other 2 groups, the odor identification deficit associated with this disorder was of the same magnitude as that observed in AD and PD, suggesting that olfactory testing cannot be used to distinguish among these 3 diseases and that the olfactory dysfunction of these disorders may reflect a common neurologic substrate.

Adult↗
PubMed1991

Polymicrobial bacteremia during long-term hemodialysis.

A review of hospital epidemiologic data disclosed five cases of polymicrobial bacteremia on a nephrology inpatient service over a period of 30 months. All five cases occurred in patients receiving long-term hemodialysis; four of them had indwelling silicone rubber vascular access devices. Although all patients had risk factors other than uremia and dialysis predisposing to an increased likelihood of infection, no patient had either obvious skin infection at the site of the vascular access or documented visceral infection. One patient died, and the other four recovered after removal of the vascular access device and appropriate antibiotic therapy. The increased risk of polymicrobial bacteremia associated with long-term hemodialysis should be taken into account when empiric antibiotic therapy is undertaken.

Adult↗