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Biomedical subjects

J Miller

Publications and source records attributed to J Miller.

At least 487 records · Page 27Linked to original sources

The fate of the aortofemoral graft.

OBJECTIVE: To determine the incidence and cause for reoperation following aortofemoral bypass surgery. DESIGN: This paper describes the results of all aortofemoral grafts performed in the years 1978-1991, 251 of these patients underwent an aortobifemoral graft (ABF) whilst the remaining 50 had an aortounifemoral graft (AUF). RESULTS: The aortofemoral bypass was the only operation performed in fewer than half of the patients. Sixteen per cent of ABF and 50% of the AUF patients had surgery before the index operation. Subsequently 33% of the ABF patients and 60% of the AUF group had one or more additional vascular procedures. Graft infections and false aneurysms continued to present in about 1% patients per year at least up to 10 years following surgery. The 5 year actuarial survival was 73% in the ABF group and 38% in the AUF patients. The primary patency at 5 years was 85% in the ABF patients and 81% in the AUF group. Amputation was performed in 6% of the ABF patients and in 20% of the AUF patients. CONCLUSIONS: The frequent need for later surgery (1:3 for the ABF patients) should be considered in the decision to undertake the initial aortofemoral operation when the patient presents with intermittent claudication.

Aneurysm, False↗

Does mental rotation require central mechanisms?

Four reaction time experiments examined the mental rotation process using a psychological refractory period paradigm. On each trial, participants made speeded responses to both a tone (S1) and a rotated letter (S2), presented with varying stimulus onset asynchronies (SOAs). If mental rotation of the stimulus letter can proceed while central mechanisms are busy with S1, then the effect of orientation should decrease substantially with decreasing SOA. Contrary to these predictions, the effect of orientation was nearly constant across SOAs, suggesting that mental rotation cannot effectively proceed without help from central mechanisms. These results support the conclusion that mental rotation requires access to a single-channel mechanism and must therefore be performed serially with other operations requiring the same mechanism.

Adult↗

Neuropsychological detection of dementia: an overview of the neuropsychological component of the Canadian Study of Health and Aging.

As part of the Canadian Study of Health and Aging (CSHA), a battery of neuropsychological measures was administered to 1879 participants. Participants who received neuropsychological evaluations were selected from an age-stratified random sample on the basis of scores on a cognitive screening tool, the Modified Mini-Mental State Examination (3MS). Seventy-five percent of the sample seen for neuropsychological evaluation scored between 50 and 77 on the 3MS and 25% of the sample scored 78 or over. This paper provides a descriptive summary of the methodological basis of the neuropsychological component of the CSHA. The findings indicated that differences existed between participants administered the battery in English or French in terms of refusal rates and diagnoses of dementia. Cursory examination of the utility of the battery indicated that the battery was tolerated well by both the participants and the psychologists involved with the study and that measures of memory functioning were central to diagnostic decision-making. The relations between neuropsychological, preliminary medical and consensus diagnoses were examined and indicated that neuropsychological information influenced diagnostic decision-making. The neuropsychology component of the CSHA is a rich source of information on persons aged 65 years and older in Canada.

Aged↗

Efficient endosomal localization of major histocompatibility complex class II-invariant chain complexes requires multimerization of the invariant chain targeting sequence.

During biosynthesis, MHC class II-invariant chain complexes are transported into endosomal compartments where invariant chain (Ii) is degraded and class II encounters antigenic peptides. One of the signals that determines this intracellular transport route has been localized to the cytosolic domain of Ii. Deletion of this signal disrupts endosomal targeting and results in the stable expression of class II-Ii complexes at the surface. In this paper we have examined the role of Ii trimerization on the generation of this endosomal localization signal. In L cell transfectants expressing class II and both wild type Ii and a truncated form of Ii that lacks this endosomal localization signal, Ii was found to form multimers which could contain both wild type and truncated Ii. The multimers were not large aggregates but were found to be discrete complexes, probably the nine molecule class II-Ii complex that has been observed in human B cells. The co-expression of truncated Ii allowed for cell surface expression of a subset of wild type Ii. This surface-expressed wild type Ii associated with truncated Ii in multimers at a 2:1 ratio, indicating that these trimers contain two truncated and one wild type Ii molecule. These data suggest a division in trafficking of Ii trimers: if two wild type Ii molecules are present, the complex is transported to and rapidly degraded in endosomes, whereas the presence of only one wild type Ii results in trafficking and expression of the heterotrimer on the cell surface. Following surface arrival, complexes containing only a single wild type Ii molecule are internalized more rapidly and have a shorter half-life than complexes containing only truncated Ii molecules. These data suggest that although a single Ii cytosolic domain can function as a plasma membrane internalization signal, multimerization of Ii is required for efficient Golgi complex to endosome targeting of class II-Ii complexes.

Animals↗

Cloning and expression of canine interleukin-10.

We describe here the cloning of canine IL-10 cDNA (GenBank accession No. U33843) and the expression of recombinant IL-10 in a dog kidney cell line (DK6247) and Chinese hamster ovary cells (CHO). Canine IL-10 exhibits strong sequence homology to the known sequences of human, mouse, rat, and bovine genes at nucleotide and amino acid levels. The IL-10 gene, when introduced into DK and CHO cell lines, produces recombinant IL-10 that causes an inhibitory effect on allogeneic MHC-driven lymphoproliferative responses.

Amino Acid Sequence↗

Mechanisms of immune tolerance induction through the thymic expression of a peripheral tissue-specific protein.

A major process through which the immune system becomes tolerant to self proteins involves the deletion of self reactive cells in the thymus. However, T cells reactive to peripheral tissue-specific proteins can escape this deletion and become tolerized in the periphery by a variety of mechanisms. We report here, contrary to expectation, that the pancreas-specific protein, elastase I, is also expressed at a low level in the thymus, and that this thymic expression contributes to tolerance induction. To study the mechanism of this tolerance induction, we utilized a double transgenic mouse model. In these mice the expression of a model protein, SV40 T antigen, is directed by the elastase I promoter and hence parallels elastase I expression in the pancreas and thymus. These mice were crossed with mice transgenic for a TCR specific for T antigen, so the majority of thymocytes and T cells in these mice express the transgene. In double transgenic mice we find that thymic expression of T antigen results in anergic thymocytes which also show a reduction of Th1 activity with no decrease in Th2 activity. These functional characteristics persist in peripheral T cells, but there is also a depletion in the number of T antigen reactive T cells in lymph nodes. Chimeras were constructed which directly demonstrated that the thymus is the site of tolerance induction and that the tolerizing element is thymic epithelium. We propose that the loss of Th1 activity as a consequence of the thymic epithelium being encountered by tissue-specific proteins results in the functional tolerization of CTL in vivo, despite the fact that CTL are fully functional in vitro. In this way autoimmune destruction is contained. Thymic expression of peripheral proteins may therefore be an additional way in which tolerance to peripheral proteins can be achieved.

Animals↗

Relationship between blood lactate concentrations and ionized calcium, glucose, and acid-base status in critically ill and noncritically ill patients.

OBJECTIVE: To determine the relationships between circulating blood lactate concentrations and several biochemical variables including ionized calcium, glucose, pH, and acid-base status in critically ill and noncritically ill patients. DESIGN: A prospective, cohort study. SETTING: The critical care research laboratory, intensive care unit (ICU), emergency room (ER), and general ward of a 466 bed university-affiliated hospital. PATIENTS: Three-hundred thirty-four critically ill and noncritically ill patients. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Circulating blood lactate concentrations, ionized calcium concentrations, blood glucose, pH, and base deficit values were simultaneously determined in blood samples from various patient populations. Descriptive data and physiologic parameters were also recorded. Circulating lactate and ionized calcium determinations were performed simultaneously in 334 whole blood samples from 334 subjects. There was neither a statistically significant nor clinically relevant correlation between circulating lactate concentrations and ionized calcium concentrations when lactate values were < or = 2 mmol/L (p = 0.8962, r2 = .01) or when lactate values were > 2 mmol/L (p = .3697, r2 = .09) in a heterogeneous patient population. Our study populations included five subject groups: a) nonhypotensive ICU patients (n = 93), b) nonhypotensive ER patients (n = 85), c) nonhypotensive general ward patients (n = 44), d) hypotensive patients from the ICU, ER, and general wards (n = 39), and e) normal controls (n = 73). There was neither a statistically significant nor clinically relevant correlation between circulating lactate concentrations and ionized calcium concentrations in each of the five populations studied for lactate values either < or = 2 mmol/L or > 2 mmol/L. We studied the relationship between circulating lactate concentrations and blood glucose concentrations (n = 334 patients), arterial pH and base deficit (n = 163 patients), and venous pH and base deficit (n = 171 patients). Statistically significant, but perhaps not clinically relevant correlations were observed when comparing circulating lactate values with blood glucose values (p = .0330, r2 = .12), arterial pH (p = .0007, r2 = .26) and base deficit from arterial specimens (p = .0014, r2 = .25). There were neither statistically significant nor clinically relevant correlations when comparing circulating lactate concentrations with venous pH (p = .9098, r2 = .01) or base deficit determined from venous blood specimens (p = .1365, r2 = .11). CONCLUSIONS: a) There is neither a statistically significant nor clinically relevant relationship between whole blood lactate concentrations and ionized calcium concentrations when studying patients with or without hyperlactatemia. b) Although there is a statistically significant correlation between circulating lactate concentrations and blood glucose concentrations, arterial pH or arterial base deficit, such associations do not appear to be clinically important.

Acid-Base Equilibrium↗

Permethrin resistance in the head louse Pediculus capitis from Israel.

Head lice, Pediculus capitis, were collected from children aged 3-12 years in Maale Adumin, a town near Jerusalem, after reports of control failure with the pyrethroid insecticide permethrin. A total of 1516 children were examined: living lice and eggs were found on 12.1% of the children; or another 22.8% of the children only nits were found. Twice as many girls as boys (8.1% v 4%) were infested with lice and or nits. Head lice collected from infested children were exposed to permethrin impregnated filter-papers. Log time probit mortality (ltp) regression lines were calculated for mortality data and compared to ltp lines for a similar collection of head lice made in 1989. The regression lines for the two years were significantly different, with a 4-fold decrease in susceptibility at the LT50 level between 1989 and 1994. The slopes of the lines also suggested that the 1994 population was more heterogenous in its response to permethrin than the 1989 population. In contrast, a laboratory population of body lice (Pediculus humanus) tested with the same batch of permethrin-impregnated papers showed a slight but non-significant increase in susceptibility between 1989 and 1994. The results suggest that resistance to pyrethroids has developed rapidly among head lice since permethrin was introduced in 1991 as a pediculicide in Israel.

Animals↗

Response complexity and precue interval effects on the lateralized readiness potential.

Fundamental properties of an important new tool in cognitive electrophysiology, the lateralized readiness potential (LRP), were examined in two experiments. Experiment 1 resolved an apparent inconsistency in the literature by demonstrating that this response-specific lateralization is larger preceding complex then preceding simple finger movements. In Experiment 2, the foveally presented precue, which indicated hand of response, preceded the go/no-go stimulus by 0, 100, 300, or 1,400 ms. Analyses of LRP latency indicated that hand-specific preparation began earlier with longer foreperiods but was temporally linked to the reaction stimulus as well as the precue. Although the degree of lateralization did not predict reaction speed in either study, a nonlateralized, response-locked negativity was larger prior to faster reactions.

Adult↗

Bicarbonate diffusion through mucus.

The mucus layer overlying duodenal epithelium maintains a pH gradient against high luminal acid concentrations. Despite these adverse conditions, epithelial surface pH remains close to neutrality. The exact nature of the gradient-forming barrier remains unknown. The barrier consists of mucus into which HCO3- is secreted. Quantification of the ability of HCO3- to establish and maintain the gradient depends on accurate measurement of this ion's diffusion coefficient through mucus. We describe new experimental and mathematical methods for diffusion measurement and report diffusion coefficients for HCO3- diffusion through saline, 5% mucin solutions, and rat duodenal mucus. The diffusion coefficients were 20.2 +/- 0.10, 3.02 +/- 0.31, and 1.81 +/- 0.12 x 10(-6) cm2/s, respectively. Modeling of the mucobicarbonate layer with this latter value suggests that for conditions of high luminal acid strength the neutralization of acid by HCO3- occurs just above the epithelial surface. Under these conditions the model predicts that fluid convection toward the lumen could be important in maintaining the pH gradient. In support of this hypothesis we were able to demonstrate a net luminal fluid flux of 5 microliters.min-1.cm-2 after perfusion of 0.15 N HCl in the rat duodenum.

Animals↗

Transurethral laser urethrotomy with argon laser: experience with 900 urethrotomies in 450 patients from 1978 to 1993.

From April 1978 to September 1993, the Department of Urology of Giessen Medical School used laser urethrotomy as standard endoscopic treatment in benign urethral strictures. In this period, 900 urethrotomies were performed in 450 patients. The majority of strictures treated were iatrogenic (65%), located in the posterior urethra (62.8%) and classified as short (< or = 1 cm) (71%). Argon laser urethrotomy was carried out in the 12 degrees position according to the technique of internal optical urethrotomy. An indwelling transurethral catheter was left for 48 h after urethrotomy. Uroflowmetry after argon laser urethrotomy revealed the efficacy of the method. A retrospective analysis of the operations was performed. Analysis showed that recurrence appeared on average after 15.2 months (range 1-39) in up to 70.1%. Nearly 50% of recurrence was evident within 1 year following surgery. Recurrence was independent of location, length and etiology of the stricture. We conclude according to our data that argon laser urethrotomy is technically feasible. Due to the high recurrence rate the method offers no advantage over conventional internal optical urethrotomy.

Humans↗

Dynamics of thin filopodia during sea urchin gastrulation.

At gastrulation in the sea urchin embryo, a dramatic rearrangement of cells establishes the three germ layers of the organism. Experiments have revealed a number of cell interactions at this stage that transfer patterning information from cell to cell. Of particular significance, primary mesenchyme cells, which are responsible for production of the embryonic skeleton, have been shown to obtain extensive positional information from the embryonic ectoderm. In the present study, high resolution Nomarski imaging reveals the presence of very thin filopodia (02-0.4 micron in diameter) extending from primary mesenchyme cells as well as from ectodermal and secondary mesenchyme cells. These thin filopodia sometimes extend to more than 80 microns in length and show average growth and retraction rates of nearly 10 microns/minute. The filopodia are highly dynamic, rapidly changing from extension to resorption; frequently, the resorption changes to resumption of assembly. The behavior, location and timing of active thin filopodial movements does not correlate with cell locomotion; instead, there is a strong correlation suggesting their involvement in cell-cell interactions associated with signaling and patterning at gastrulation. Nickel-treatment, which is known to create a patterning defect in skeletogenesis due to alterations in the ectoderm, alters the normal position-dependent differences in the thin filopodia. The effect is present in recombinant embryos in which the ectoderm alone was treated with nickel, and is absent in recombinant embryos in which only the primary mesenchyme cells were treated, suggesting that the filopodial length is substratum dependent rather than being primary mesenchyme cell autonomous. The thin filopodia provide a means by which cells can contact others several cell diameters away, suggesting that some of the signaling previously thought to be mediated by diffusible signals may instead by the result of direct receptor-ligand interactions between cell membranes.

Animals↗

Early development of acute myelogenous leukemia following kidney transplantation: possible role of multiple serum cytokines.

We report a patient who at the time of kidney transplantation for polycystic kidney disease was found to have an enlarged inguinal lymph node which later demonstrated evidence of extra medullary granulopoiesis. During the first two weeks following kidney transplantation, a striking leukemoid pattern developed and 2 months after transplant the patient was diagnosed with acute myelogenous leukemia (AML). Retrospective analysis of peripheral blood cytokines over this time revealed elevated levels of GMCSF and gamma IFN at the time of peak peripheral blood WBC with subsequent peaks in IL-4, IL-6 and IL-2 as the peripheral blood WBC fell. A rise in levels of TNF alpha also preceded the peripheral blood WBC rise (although these concentrations were at or below those following uncomplicated kidney transplants). The clinical course of AML in this patient was marked by relentless relapse despite chemotherapy. The possibility of cytokine facilitated tumor growth is discussed.

Adult↗

Can mental rotation begin before perception finishes?

We conducted six experiments to determine if mental rotation can begin before perception finishes, as allowed by continuous flow models but not discrete state models of information processing. The results of Experiments 1-3 showed that the effect of shape discriminability on RT was underadditive with the effect of stimulus orientation, suggesting that mental rotation began before shape discrimination had finished and that the two processes overlapped in time. The results of experiments 4-6 indicated that mental rotation can overlap with color discriminations as well. In both sets of experiments, however, the amount of underadditivity tended to be much less than predicted by models allowing interference-free overlap. This suggests that mental rotation can overlap with perceptual analysis, contrary to fully discrete models, but that little rotation is carried out during this overlap due to interference between simultaneous discrimination and rotation processes.

Adult↗

Negative priming depends on ease of selection.

Negative priming effects have been offered as evidence that distractor stimuli are identified. We conducted two experiments to determine if such effects occur even when it is easy to discriminate target from distractor stimuli. In Experiment 1, we found the usual negative priming effect when target and distractor positions varied from trial to trail, but not when these positions remained fixed. Experiment 2 extended these results to a situation where the ease of selection varied only in the prime display. These findings argue that irrelevant inputs can be filtered out prior to stimulus identification under certain circumstances and therefore pose problems for strict late selection theories.

Adolescent↗