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Biomedical subjects

C A Miller

Publications and source records attributed to C A Miller.

At least 19 recordsLinked to original sources
PubMed1992

Platelet and fibrinogen survival in calves implanted with artificial heart and ventricular assist device--correlation with autopsy findings.

The two main ingredients of blood clots formed on artificial surface are platelets and fibrinogen. In this study, we measured platelet and fibrinogen survival in calves implanted with total artificial heart (TAH) and left ventricular assist device (LVAD), and correlate these data with autopsy findings. Platelet survival with autologous 111In-labeled platelets was performed on nine calves implanted with TAH and five with LVAD. Fibrinogen survival with 131I-labeled homologous fibrinogen was performed on six calves with TAH and three with LVAD. Platelet survival was significantly shortened in both groups of animals: 5.89 +/- 0.52 days, control 6.46 +/- 0.31 days, p = 0.0013; fibrinogen survival was normal: 8.79 +/- 1.20 days, control 8.64 +/- 1.16 days. At autopsy two calves with TAH had multiorgan thromboembolism. Two other animals with TAH and four with LVAD had focal renal infarcts. Most animals had minor clot formation within the prosthetic device. Major septic complications occurred in four calves with TAH and one with LVAD. Continuous platelet activation by artificial surface probably explains the shortened platelet survival and thromboembolic complications.

Animals↗
PubMed1992

Surgical treatment of the spontaneous spinal epidural abscess.

Seven cases of spontaneous epidural abscess are reviewed. Three patients had posterior abscesses and no evidence of vertebral body osteomyelitis. These patients had excellent outcomes with laminectomies and antibiotics. Because of significant vertebral destruction, two patients with vertebral osteomyelitis required posterior fixation after laminectomy. Two other patients with vertebral osteomyelitis had complete destruction of the vertebral body and required anterior decompression and fusion in addition to posterior fixation. In the four patients with vertebral osteomyelitis, morbidity was high, reflecting their age and significant medical problems. This review supports the contention that medically stable patients with posterior epidural abscesses can be treated with laminectomy and antibiotics with little risk of progressive instability. The proper surgical treatment of anterior epidural abscesses secondary to osteomyelitis requires knowledge about the amount of destruction of the supporting columns, the amount of neural compression secondary to the purulence, and the patient's general medical condition.

Abscess↗
PubMed1992

Magnetic resonance imaging of trauma to the thoracic and lumbar spine. The importance of the posterior longitudinal ligament.

Magnetic resonance imaging was used to evaluate 24 patients with injuries to the thoracic, thoracolumbar (T12-L1), or lumbar spine. Correlation of the magnetic resonance imaging findings to surgical therapy and outcome was evaluated, with particular attention to the longitudinal ligaments. The ability of the magnetic resonance imaging to detect the extent of trauma to the spinal cord parenchyma and to the anterior and posterior longitudinal ligaments was found to be important in guiding the surgical approach to these spine fractures.

Adolescent↗
PubMed1992

Characterization of neutral proteinases from Alzheimer-affected and control brain specimens: identification of calcium-dependent metalloproteinases from the hippocampus.

Three neutral proteinases from human hippocampal tissue have been identified and partially characterized using substrate gel electrophoresis. The proteinases showed activity when gelatin was used as the substrate, but had no detectable activity against casein. Based on the results of inhibition studies and the calcium requirements, it was concluded that the activities were due to calcium-dependent metalloproteinases. The apparent molecular weights were 130,000 (MP-130), 100,000 (MP-100), and 70,000 (MP-70). Half-maximal activities were observed with 20 microM Ca2+ for MP-130, 40 microM Ca2+ for MP-100, and 800 microM Ca2+ for MP-70. In the presence of Ca2+, Zn2+ reestablished the activities of the three metalloproteinases at a lower concentration than did either Co2+ or Mn2+. One millimolar Al3+ inhibited 67% of the MP-70 activity, but did not affect the MP-100 and MP-130 activities. An analysis of Alzheimer-affected hippocampal and control samples showed that the specific activity (in units per milligram of sodium dodecyl sulfate-soluble protein) of MP-70 varied less than the activities of MP-100 and MP-130 between the two groups. Although p-amino-phenylmercuric acetate (p-APMA) increased the activities of MP-70 by 70% in both groups of specimens, the resulting activities from Alzheimer samples were greater than those from control samples (p less than 0.01). A wide range of MP-100 specific activity was observed in both groups, and its mean activity was higher in Alzheimer-affected samples (p less than 0.05). Treatment with p-APMA increased the activity of MP-100 only 25% in both groups of tissue samples. MP-130 activity was detected predominantly in Alzheimer-affected hippocampal specimens, and treatment with p-APMA failed to increase its activity in both the control and the Alzheimer-affected specimens. The results demonstrate an elevated level of metalloproteinase activities, capable of degrading tissue matrix components, in the hippocampus from postmortem Alzheimer patients.

Aged↗
PubMed1992

Glucocorticoids exacerbate kainic acid-induced extracellular accumulation of excitatory amino acids in the rat hippocampus.

Glucocorticoids (GCs) compromise the ability of hippocampal neurons to survive various insults, and do so, at least in part, by exacerbating steps in the glutamate/N-methyl-D-aspartate (NMDA)/calcium cascade of damage. As evidence, GCs impair uptake of glutamate by hippocampal astrocytes, the GC endangerment of the hippocampus is NMDA receptor dependent, and GCs exacerbate kainic acid (KA)-induced calcium mobilization. These observations predict that GCs should also exacerbate KA-induced accumulation of extracellular glutamate and aspartate. To test this, adrenalectomized rats were given replacement GCs in either the low or high physiological range. Three days later, rats were anesthetized and 1 mM KA was infused through a dialysis probe placed in the dorsal hippocampus. Extracellular amino acid concentrations in the dialysate were then assessed by HPLC. After KA infusion, high-GC rats (30 +/- 3 micrograms/dl) had significantly elevated concentrations of glutamate and aspartate compared with low-GC rats (all less than 0.95 micrograms/dl). The glutamate accumulation was due to GCs raising pre-KA concentrations, whereas the aspartate accumulation was due to GCs exacerbating the KA-induced rise. Glutamine concentrations were unaffected by KA, whereas the high-GC regimen elevated glutamine concentrations both before and after KA. Taurine concentrations rose after infusion of KA, but were unaffected by GC regime, whereas alanine concentrations were unaffected by either manipulation. Serine concentrations were unaffected by KA, but were depressed both before and after KA in high-GC rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

Radionecrosis secondary to interstitial brachytherapy: correlation of magnetic resonance imaging and histopathology.

Radiation-induced tissue damage in the central nervous system is a well-known complication of interstitial brachytherapy for brain tumors, yet imaging correlates have historically been based upon computed tomographic scans. We now present magnetic resonance imaging (MRI) to correlate radiation changes after interstitial brachytherapy with the histopathology. The central nervous system of a 38-year-old man with a left frontal cerebral glioma diagnosed by stereotactic biopsy was treated with interstitial brachytherapy (iridium-192, 47 Gy), followed by limited-field irradiation (45 Gy). With progressive deterioration, a second biopsy demonstrated radiation changes. Despite aggressive medical management, the patient died 9 months after completion of radiation therapy. Postmortem evaluation compared MRI scans of the intact, fixed brain with the histopathology. Axial sections (10 mm) obtained by MRI scan and autopsy brain slices were cut in the identical plane. Neuroimaging and histopathological findings of the lesion correlated within 2 to 3 mm resolution. In the peripheral white matter, MRI scan did not indicate the extent of radiation effect histologically. We suggest that MRI has limited utility in assessing the extent of impact of radiation on surrounding brain.

Adult↗
PubMed1992

Magnetic resonance imaging and pathological correlates of meningiomas.

We examined the relationships between specific magnetic resonance imaging features and certain gross and microscopic characteristics of meningiomas, including vascularity, gross texture (consistency), and venous sinus involvement. Magnetic resonance imaging scans, surgery reports, and the histopathological findings of tumors were examined retrospectively in 54 patients. Sinus involvement was accurately predicted on T1-weighted images in 9 of 10 cases (P = 0.001) and tumors with cystic changes in 3 of 3 cases. T1-weighted images were not useful for predicting vascularity unless actual flow voids could be visualized (five of six cases). There was no correlation between T1 signal intensity, tumor consistency, or histological findings. In tumors without detectable vascularity on T1-weighted images, hyperintensity relative to gray matter on T2-weighted images was correlated with increased vascularity (P = 0.004). Tumors with soft consistency (P = 0.007), cellular atypia, invasion, angioblastic, or melanocytic components were also hyperintense, compared with gray matter on T2-weighted images (P = 0.0266). Aggressive meningiomas were found to be more vascular (P = 0.045). No correlation was found between the degree of surrounding edema or contrast enhancement with histopathological findings, vascularity, or consistency.

Brain↗
PubMed1992

Ventricular assist devices for postcardiotomy cardiogenic shock. A combined registry experience.

Data submitted voluntarily to the combined registry since its inception in 1985 to December 31, 1990, on the use of ventricular assist devices for postcardiotomy cardiogenic shock in 965 patients were analyzed. Approximately 45% of patients were weaned from temporary circulatory assistance and 24.6% reached hospital discharge regardless of the original operation. In 90% of patients who were discharged from the hospital, circulatory support was able to be discontinued by 1 week. Rates of weaning and discharge were statistically different and favored those patients requiring univentricular support only. Results were equal whether nonpulsatile centrifugal or pulsatile pneumatic devices were used for support. Although complications were frequent and multiple during assist pumping, patient variables including age greater than 70 years rather than direct complications caused by circulatory support were likely to affect overall outcome. In patients achieving hospital discharge, 2-year actuarial survival was 82% with 86% of patients being in New York Heart Association functional class I or II. In rare instances of device dependency in 43 patients (4.5%) with no contraindications to transplantation, 32 (74.4%) underwent bridge to cardiac transplant and 20 (62.5%) were discharged. This multi-institutional experience would continue to support the use of ventricular assist devices in postcardiotomy cardiogenic shock.

Adolescent↗
PubMed1992

American Academy of Pediatrics. Preventive health care for young children: Findings from a 10-country study and directions for United States policy.

Infant health and survival in the US compare unfavorably with other Western industrial democracies. Circumstances that contribute to favorable pregnancy outcomes in other countries include nearly complete participation of pregnant women in early prenatal care and linkage of care to extensive support benefits. The study reported here extends these earlier observations to preventive health services for children from infancy through adolescence and to the social benefit programs that support their families. This report looks at the condition of children in 10 European countries: Belgium, Denmark, France, the Federal Republic of Germany, Ireland, the Netherlands, Norway, Spain, Switzerland, and the United Kingdom. All of these countries have better infant survival rates than the US, and they all share elements of pluralism in their systems of health care.

Adolescent↗
PubMed1991

Identification of an allatostatin from the tobacco hornworm Manduca sexta.

A peptide (Manduca sexta allatostatin) that strongly inhibits juvenile hormone biosynthesis in vitro by the corpora allata from fifth-stadium larvae and adult females has been purified from extracts of heads of pharate adult M. sexta by a nine-step purification procedure. The primary structure of this 15-residue peptide has been determined: pGlu-Val-Arg-Phe-Arg-Gln-Cys- Tyr-Phe-Asn-Pro-Ile-Ser-Cys-Phe-OH, where pGlu is pyroglutamate). To our knowledge, this neuro-hormone has no sequence similarity with any known neuropeptide from other organisms. The synthetic free acid and amide forms showed in vitro activity indistinguishable from that of native M. sexta allatostatin. The ED50 of synthetic M. sexta allatostatin on early fifth stadium larval corpora allata in vitro was approximately 2 nM. This inhibition was reversible. In a cross-species study, M. sexta allatostatin also inhibited the corpora allata of adult female Heliothis virescens but had no effect on the activity of corpora allata of adult females of the beetle Tenebrio molitor, the grasshopper Melanoplus sanguinipes, or the cockroach Periplaneta americana.

Amino Acid Sequence↗
PubMed1991

Gyrase-dependent stabilization of pSC101 plasmid inheritance by transcriptionally active promoters.

The pSC101 plasmid encodes a cis-acting genetic locus termed par that ensures the stable inheritance of plasmids in a population of dividing cells. In the absence of selection, par-defective plasmids are lost rapidly from the bacterial population. We report here that the stability of par-deleted pSC101 derivatives is restored by introducing certain adventitious bacterial promoters onto the plasmid. Stabilization requires active transcription from the inserted promoter and is affected by the site and orientation of the insertion, the length of the nascent transcript and DNA gyrase activity. While a promotor-associated overall increase in negative superhelicity of plasmid DNA was observed, stabilized inheritance appeared to be dependent on localized rather than generalized supercoiling. Our demonstration that promoter-induced DNA supercoiling can mimic the effects of the pSC101 par locus provides evidence that the previously reported superhelicity-generating effects of par are intrinsic to its function.

DNA Topoisomerases, Type II↗
PubMed1991

Alzheimer's and Parkinson's disease. Brain levels of glutathione, glutathione disulfide, and vitamin E.

Human brain levels of glutathione (GSH), glutathione disulfide (GSSG), and vitamin E were measured in neurologically normal control patients and two groups of patients with neurodegeneration: those with Alzheimer's disease (AD), and AD with some features of Parkinson's disease (AD-PD). Control brain samples contained GSH levels more than 50 times higher than GSSG. The levels of GSH were highest in the caudate nucleus and lowest in the medulla. In patients with AD or AD-PD, hippocampal levels of GSH were significantly higher than controls. Patients with AD also demonstrated high GSH levels in the midbrain compared to normal. In contrast, patients with AD-PD did not have significantly elevated GSH levels in this site. GSSG levels were not significantly different in any brain region between controls and diseased patients. In control brains, the medulla had higher levels of vitamin E than any other brain region. The caudate nucleus had the lowest levels, which were about half the levels in the medulla. Control levels of vitamin E in the midbrain were about 18.8 micrograms/g. In AD patients the midbrain levels of vitamin E doubled to 42.3 micrograms/g. This doubling also occurred in AD-PD patients where midbrain vitamin E levels increased to 44.0 micrograms/g. These results may indicate that compensatory increases in GSH and vitamin E levels occur following damage to specific brain regions in patients with AD or AD-PD.

Aged↗
PubMed1991

Broken agreement.

The subjects and verbs of English sentences agree in number. This superficially simple syntactic operation is regularly implemented by speakers, but occasionally derails in sentences such as The cost of the improvements have not yet been estimated. We examined whether the incidence of such errors was related to the presence of subject-like semantic features in the immediate preverbal nouns, in light of current questions about the semantic versus syntactic nature of sentence subjects and the interactivity of language processing. In three experiments, speakers completed sentence fragments designed to elicit erroneous agreement. We varied the number and animacy of the head noun and the immediate preverbal (local) noun, as well as the amount of material separating the head noun from the verb. The plurality of the local noun phrase had a large and reliable effect on the incidence of agreement errors, but neither its animacy nor its length affected their occurrence. The latter findings suggest, respectively, that the semantic features of sentence subjects are of minimal relevance to the syntactic and morphological processes that implement agreement, and that agreement features are specified at a point in processing where the eventual length of sentential constituents has little effect on syntactic planning. Both results follow naturally from explanations of language production that emphasize the segregation of sentence formulation processes into relatively autonomous components.

Adult↗
PubMed1991

Complexing of actin and other nuclear proteins to DNA by cis-diamminedichloroplatinum(II) and chromium compounds.

Actin was found to be the major protein crosslinked to the DNA of intact Chinese hamster ovary cells that were treated with either potassium chromate (hexavalent) or cis-diamminedichloroplatinum(II) (cis-platinum). This protein was identified as actin by its mol. wt (45 kd), its isoelectric point (pI = 5.4), positive reactivity with an actin antibody, and by protease mapping. Additionally, a purified actin standard migrated to the same location in a two-dimensional gel system as p45. Actin comprised approximately 20% of the protein component in chromate-induced DNA-protein crosslinks. In addition, to actin, several other major proteins (e.g. 53 kd, pI = 5.2, 50 kd, pI = 9) were crosslinked to DNA following exposure to cis-platinum or chromate. These proteins were abundant in the nuclear matrix fraction. Hexavalent chromate is the toxicologically active form because it is readily taken up into cells by an anion transport system. In contrast, trivalent chromium is considerably less toxic because it cannot enter the cell; however, most of the hexavalent form is eventually reduced to the trivalent form inside the cell. Previous studies have suggested that the trivalent form of chromium participates in complexing DNA with proteins. DNA-protein crosslinks were formed in isolated nuclei or in mixtures of purified DNA and protein incubated with trivalent chromium. However, the formation of these complexes required at least 16 h of incubation to exchange the parent compound ligands. Hexavalent chromate did not form these complexes in vitro under similar conditions. Incubation of trivalent chromium with purified actin and DNA resulted in DNA-actin crosslinks as detected by an electrophoretic mobility different from that of either free actin or DNA when the complex was transferred from a gel to nitrocellulose and stained for protein. These studies describe a new technique for detecting DNA-protein complexes and demonstrate that actin-DNA structures in intact cells create sites that selectively react with metal DNA-protein crosslinking agents.

Actins↗
PubMed1991

Severity of dementia in Alzheimer disease and neurofibrillary tangles in multiple brain regions.

We studied the relationship of numbers of neurofibrillary tangles (NFTs) in selected cortical and subcortical sites to the duration of clinical disease and severity of dementia. Sixteen patients with a clinical diagnosis of "probable" Alzheimer disease were screened with standardized neuropsychological instruments to estimate the severity of dementia. Tissues were obtained at autopsy from the subiculum, four neocortical areas, and the nucleus basalis of Meynert: NFT counts were assessed with the thioflavin S stain. Overall, the subiculum showed the most NFTs, followed by visual association and premotor cortices, primary cortex (motor and visual), and the nucleus basalis. NFT counts were significantly positively correlated with the duration of disease in the nucleus basalis and less strongly in the motor cortex. Neuropsychological impairment was significantly correlated with NFT counts only in the nucleus basalis. In turn, counts in the nucleus basalis were reliably correlated with those in all other brain regions except the subiculum. Counts in the subiculum showed no correlation with any other area. Numbers of NFTs within functionally related sites, the primary motor and premotor cortices or primary and visual association cortices, were significantly or near-significantly correlated, whereas motor and visual cortical counts showed no intercorrelation. Our results indicate that although there is less NFT accumulation in the nucleus basalis than in many other brain regions, counts in this structure bear a close relationship to disease severity and duration and to NFT accumulation in other regions.

Aged↗
PubMed1990

Role of DNA superhelicity in partitioning of the pSC101 plasmid.

Previous work has shown that a cis-acting locus (termed par for partitioning) on the pSC101 plasmid accomplishes its stable inheritance in dividing cell populations. We report here that the DNA of pSC101 derivatives lacking the par region shows a decrease in overall superhelical density as compared with DNA of wild-type pSC101. Chemicals and bacterial mutations that reduce negative DNA supercoiling increase the rate of loss of par plasmids and convert normally stable plasmids that have minimal par region deletions into unstable replicons. topA gene mutations, which increase negative DNA supercoiling, reverse the instability of partition-defective plasmids that utilize the pSC101, p15A, F, or oriC replication systems. Our observations show that the extent of negative supercoiling of plasmid DNA has major effects on the plasmid's inheritance and suggest a mechanism by which the pSC101 par region may exert its stabilizing effects.

DNA Topoisomerases, Type I↗
PubMed1990

Degeneration of spinocerebellar neurons in amyotrophic lateral sclerosis.

The selective involvement of spinocerebellar neurons in sporadic amyotrophic lateral sclerosis was investigated using two monoclonal antibodies that have neuronal subset specificity in human spinal cord. In normal control subjects, monoclonal antibody 6A2 showed specificity for neurons of the dorsal nucleus of Clarke, the cells of origin of the dorsal spinocerebellar tract. Immunoreactive neurons were also observed in locations corresponding to the central cervical nucleus and spinal border region, containing neurons of the cervicospinocerebellar and ventral spinocerebellar tracts, respectively. The latter two neuronal subsets are indistinguishable from surrounding neurons when conventional histological stains are used. Antigen 6A2 was distributed on surfaces of neuronal somas and proximal neurites and extended into the extracellular space. A second antibody, monoclonal antibody 44.1, labeled the cytoplasm of neuronal somas and neurites, including all monoclonal antibody 6A2-reactive cells and alpha motoneurons. In spinal cords of all 5 patients with amyotrophic lateral sclerosis, monoclonal antibody 6A2 reactivity in the majority of spinocerebellar neurons was absent or localized to the somal cytoplasm, which still stained with monoclonal antibody 44.1. In more severely involved tissues, there was loss of some spinocerebellar neurons and a corresponding loss of monoclonal antibody 44.1 reactivity. These findings confirm involvement of the spinal cord components of the spinocerebellar system at all levels in sporadic amyotrophic lateral sclerosis and suggest that some surface molecules are modified during the degenerative process.

Adult↗