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Biomedical subjects

M Haas

Publications and source records attributed to M Haas.

At least 199 records · Page 11Linked to original sources

The rationing of health care: should Oregon be transported to Australia?

The Oregon Plan is an ambitious attempt to address the widespread problem in the United States of a growing number of individuals who are without private health insurance and are not eligible for federal assistance programs. Its aim is to provide universal access for all Oregonians, without increasing total health care expenditure, by restricting the cover of some treatments. It has aroused interest in Australia and elsewhere. The appeal of the Oregon Plan lies in its explicit approach to rationing, in community participation in setting priorities, and the use of a cost-effectiveness framework. This paper describes the beginnings and the development of the Oregon Plan, and compares the actual development of the Plan with the rhetoric. There is a gap between the rhetoric of the Plan and its reality. The Oregon plan should be considered in the context of the United States health care system. We compare the American problems with those facing the Australian health care system and conclude that the answer to the question of whether Oregon should be transported to Australia is no. Nevertheless there are elements of the rhetoric of the Plan which could be applied in rationing health care in Australia.

Health Care Rationing↗

Na-K-Cl cotransport in the shark rectal gland. I. Regulation in the intact perfused gland.

To investigate regulation of the Na-K-Cl cotransport system in the rectal gland of the dogfish shark Squalus acanthias, we examined binding of the loop diuretic [3H]benzmetanide to the intact gland. Glands were perfused with a shark Ringer solution, either in a basal state or stimulated with vasoactive intestinal peptide (VIP). [3H]benzmetanide was added to the perfusion solution for the last 25 min of perfusion, after which the gland was homogenized and the amount of bound [3H]benzmetanide was determined in the membrane fraction. Most of the membrane-associated [3H]-benzmetanide appeared to be associated with the Na-K-Cl cotransporter as judged by the dissociation rates at 0 degree C and 20 degrees C, by labeling with a photosensitive analogue, and by continued association of [3H]benzmetanide with membrane protein on solubilization. With the use of [3H]4-benzoyl-5-sulfamoyl-3-(3- thenyloxy)benzoic acid, a photosensitive analogue of benzmetanide, a 200-kDa protein was selectively labeled on exposure to ultraviolet light. It was also possible to detect [3H]-benzmetanide binding during the perfusion period as an arterial-venous difference, thereby providing a time course of the binding process. In comparing two groups of five glands each, VIP stimulated NaCl secretion 20-fold and [3H]benzmetanide binding 16-fold, providing strong evidence that the Na-K-Cl cotransport system is activated as part of the process of stimulation of secretion. The VIP-stimulated increase in [3H]benzmetanide binding was completely inhibited when Ba was added to the perfusate to block K channel-mediated K exit across the basolateral membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Deposition and removal of cutaneous beta 2-microglobulin.

These studies were designed to track the cutaneous deposition of beta 2-microglobulin (beta 2M) in patients on chronic hemodialysis, patients with chronic renal insufficiency and patients with successful renal transplants. Immunoperoxidase staining of skin biopsies from dialysis patients demonstrated significantly increased amounts of beta 2M compared to controls (p < 0.01). There was a strong positive correlation between the skin beta 2M content and the years of dialysis treatment. Renal transplant recipients had decreased skin content of beta 2M compared to hemodialysis patients. There was no difference in the skin beta 2M content in patients with chronic renal insufficiency not on hemodialysis and controls. No dialysis patient had amyloid in the skin by Congo red stain. We conclude that beta 2M accumulates in the skin of patients on chronic hemodialysis. This beta 2M is not in the form of amyloid. Successful renal transplantation allows for the removal of beta 2M from the skin indicating that beta 2M not in the form of amyloid can be mobilized from tissue sites.

Adult↗

Lumbar motion trends and correlation with low back pain. Part II. A roentgenological evaluation of quantitative segmental motion in lateral bending.

OBJECTIVE: A radiographic study was undertaken to describe the relationship between the magnitude of coupled lumbar motion in lateral bending and the presence of low back pain: correlation between pain and motion, relationship between motion category and motion and symmetry of lumbar motion. DESIGN: Survey. SETTING: Chiropractic college student health center and private chiropractic clinic. PARTICIPANTS: 249 subjects: 114 with low back pain, 29 asymptomatic with no history and 106 asymptomatic with history. Of these, 194 were freshman volunteers and 55 were new private clinic low back pain patients. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Net lumbar segmental tilt and rotation in lateral bending: corrected and uncorrected for segmental malposition with the patient standing in the upright neutral position. RESULTS: Statistical analysis demonstrated no significant relationship between coupled lumbar motion and low back pain (p greater than .01). The presence of type II motion could account for, on average, less than 5% loss of segmental tilt in the lumbar spine. Asymmetries between left and right side motion averaged 45 to 100% of unilateral range of motion. CONCLUSIONS: This study suggests that back pain is not an indication for the routine use of lateral bending films for the identification of alterations in the magnitude of lumbar segmental motion in lateral bending. It further indicates that type II motion cannot be ruled out as a normal variant. The paucity of symmetrical lumbar motion suggests that segmental tilt or coupled rotation asymmetry, in and of itself, should not be considered an indication for spinal manipulation.

Adolescent↗

Diagnostic utility of the McGill Pain Questionnaire and the Oswestry Disability Questionnaire for classification of low back pain syndromes.

Verbal pain description and assessment of functional limitations are key components in the clinical evaluation of patients with low back pain syndromes. Using the McGill Pain Questionnaire (MPQ) to quantify the pain experience and the Oswestry Disability Questionnaire (ODQ) to quantify functional disability, a study was undertaken to determine the efficiency with which the MPQ and ODQ were capable of enhancing the differential diagnosis of three broad categories of low back syndromes. Three discriminative models were employed. The combined discriminant model (MPQ/ODQ) yielded the highest accuracy, 0.90, and it was the only model with acceptable predictive power. The greatest utility of the discriminant models was found to be ruling out nonspecific low back pain and ruling in radiculopathy, with and without neurological deficits. Subjective pain and disability appear to have the potential for successfully differentiating broad categories of low back pain. Further studies need to be performed to assess the discriminant power of the MPQ and ODQ for specific diagnostic entities.

Activities of Daily Living↗

Role of the p53 tumor suppressor gene in the pathogenesis and in the suppression of acute lymphoblastic T-cell leukemia.

The tumor suppressor gene p53 has been shown to be mutated in 50% of acute lymphoblastic T-cell-leukemia (T-ALL) cell lines, all of which were established from T-ALL cases in relapse. In these lines both alleles of the p53 gene were independently affected by point mutation. In contrast, in human solid tumors possessing a mutated p53 allele, the second wild-type p53 suppressor allele is often lost by deletion rather than altered by mutation. This suggests that in T-ALL cell lines, the product encoded by the second mutated allele provides the cells with an additional oncogenic stimulus, beyond the loss of suppressive activity. While different p53 mutations have been shown to possess differential oncogenic potential in the p53 plus ras cotransformation assay, in T-ALL cells different mutations may in addition possess distinct functions, further contributing to the tumorigenic phenotype.

Animals↗

[Clinical results and material behavior of composite, ceramic and gold inlays].

Laboratory-manufactured gold, ceramic and composite inlays were compared with the CAD/CAM produced CEREC inlay experimentally and clinically. The following systems were examined: Dicor, Optec, Hi-Ceram, Du-Ceram, Cerec, Kulzer, Coltene, SR-Isosit composite inlays, and gold inlays (Degulor C) with adhesive fixation (group I) and with zinc oxide phosphate cement (group II). In the clinical trial inlays in 270 teeth were re-evaluated in a total of 73 patients after 2.3 to 5 years. After 3 years the results obtained with Optec, Hi-Ceram and the Coltene composite inlay were less favorable than those of other systems--statistically however, this difference was of rather low significance (p less than 0.05). Fractures of ceramic inlays occurred in 6 cases within 8 months. 10 failures of ceramic and composite inlays were due to secondary caries.

Composite Resins↗

[3H]bumetanide binding to mouse kidney membranes: identification of corresponding membrane proteins.

Crude plasma membranes from whole mouse kidneys have two classes of [3H]bumetanide binding sites. High-affinity sites (K1/2 approximately equal to 0.04 microM; Bmax = 1-2 pmol/mg protein) are similar to those identified on dog kidney membranes (B. Forbush and H.C. Palfrey. J. Biol. Chem. 258: 11787-11792, 1983) both with respect to affinity and in that Na, K, and Cl are required for [3H]bumetanide binding. Low-affinity sites (K1/2 approximately equal to 1 microM; Bmax = 7-14 pmol/mg) are unaffected by removal of these ions; such sites are not seen with dog kidney. When mouse kidney membranes are photolabeled with 4-[3H]benzoyl-5-sulfamoyl-3-(3-thenyloxy)benzoic acid [( 3H]BSTBA), a photoreactive bumetanide analogue, specific incorporation of the label is seen in two regions. As with dog kidney [M. Haas and B. Forbush. Am. J. Physiol. 253 (Cell Physiol. 22): C243-C252, 1987], an approximately 150-kDa protein is labeled with high affinity (K1/2 approximately equal to 0.05 microM). This labeling also requires Na, K, and Cl and appears to correspond to the high-affinity [3H]bumetanide binding sites and to the Na-K-Cl cotransport system. A second peak of [3H]BSTBA photolabeling, centered at approximately 75 kDa, incorporates the label with lower affinity (K1/2 = 2-3 microM). The photolabeling at approximately 75 kDa is unaffected by Na, K, and Cl concentrations and thus may correspond, at least in part, to the low-affinity [3H]bumetanide binding sites. Western blot analysis of [3H]BSTBA-labeled mouse kidney membranes was performed using an antiserum raised to proteins of approximately 82 and approximately 39 kDa isolated from mouse Ehrlich ascites tumor cells using a bumetanide affinity gel (P. B. Dunham, F. Jessen, and E. K. Hoffmann. Proc. Natl. Acad. Sci. USA 87: 6828-6832, 1990). This antiserum cross-reacts with a approximately 150-kDa mouse kidney protein, the staining profile of which on Western blot corresponds very closely to the peak of specific [3H]BSTBA incorporation in this region. The antiserum also reacts with proteins in the range of 65-85 kDa, overlapping the low-affinity peak of [3H]BSTBA incorporation.

Affinity Labels↗

Intrabacterial sodium-to-potassium ratios and ATP contents of Mycobacterium leprae from ofloxacin-treated patients.

In a clinical trial including 17 multibacillary leprosy patients the in vivo effectiveness of ofloxacin on Mycobacterium leprae was tested via mass spectrometric determination of intrabacterial ratios of the concentrations of the sodium and potassium ions of individual organisms and of the ATP content per 10(6) bacteria isolated from skin biopsies. After 3 months of treatment, the in vivo drug effect could be determined with at least one of the two methods in 14 cases. Both methods revealed that in two cases the bacteria definitely did not respond to a 3-month ofloxacin monotherapy (200 mg twice daily). In three further cases a nonresponse of the M. leprae organisms was suspected from the mass spectrometric measurements. In the responder cases, the M. leprae were severely impaired. From the intrabacterial cation ratios the percentage of viable organisms averaged over all untreated biopsies was determined to be 58% and the percentage-killing during the first 3 months of treatment was 72%.

Adenosine Triphosphate↗

[Caries status and periodontal health in 6- to 10-year old elementary school children in Graz compared to Swiss, Swedish and WHO principles].

In a complete survey, 7500 primary pupils in Graz aged between six and ten years were examined for caries and periodontal health. Comparison with the DMF-T values of primary school pupils in Switzerland and Sweden indicated that considerable efforts are required in Austria if preventive dental health education is to achieve the standard status it has enjoyed for years in the other countries mentioned.

Austria↗

Statistical methodology for reliability studies.

Although a considerable number of reliability studies have appeared in the chiropractic literature in the last 10 yr, there is still no consensus on the definition of reliability, appropriate statistics for reliability testing or interpretation of results. This paper offers suggestions for the standardization of experimental design, analysis and evaluation for reliability studies. The primary focus is on appropriate concordance statistics, i.e., Kappa and intraclass correlation. These are presented in detail, together with a discussion of their limitations. Less suitable, but often used indices such as Pearson's r are also discussed. A measure of precision, the interexaminer measurement error, is introduced and a methodology for evaluating precision is presented. Clinical issues which must be considered in reliability studies are discussed; specifically, those issues relevant to studies of diagnostic indicators for spinal manipulation.

Analysis of Variance↗

Interexaminer reliability for multiple diagnostic test regimens.

A methodology is presented for conducting interexaminer reliability studies when indication for adjustment is based on the outcomes of multiple diagnostic procedures. The adjustment decision-making process is simulated by defining multitest scores to be computed from test battery results and defining threshold values of these scores to demarcate the selection/rejection decision made by the clinician. A probability analysis of random chance agreement suggests that intermediate values of the threshold multitest scores must be used to ensure moderate agreement between observers and the viability of concordance statistics.

Chiropractic↗

Determination of in vivo and in vitro drug effects of mycobacteria from the mass spectrometric analysis of single organisms.

Laser microprobe mass analysis of single bacterial organisms allows the determination of their intrabacterial ratio of sodium-to-potassium ions and the registration of fragment ions originating from their organic bacterial cell matrices as mass fingerprint spectra. It has been established previously that the intrabacterial cation ratio provides information on the physiological state of an individual bacterial cell. In the present experiments it is also shown, with different cultivable mycobacterial species and strains (drug sensitive and resistant) exposed to various drugs, that data derived from the evaluation of the mass fingerprint spectra reflect changes in the degree of impairment. The analysis of Mycobacterium leprae derived from a limited number of skin biopsies of lepromatous/borderline lepromatous leprosy patients under World Health Organization-recommended multiple-drug therapy (WHO/MDT) showed impairment of the organisms with both of the methods of measurement in proportion to the duration of treatment except in one case. In one M. leprae population from a patient who had been treated for 19 months, the fingerprint evaluation gave the first evidence for an insufficient response to treatment. This was further confirmed by the unusual frequency distribution of the Na+,K+ ratios which revealed the existence of two subpopulations, one impaired and one unimpaired.

Anti-Bacterial Agents↗

The regulation of Na/K/2Cl cotransport and bumetanide binding in avian erythrocytes by protein phosphorylation and dephosphorylation. Effects of kinase inhibitors and okadaic acid.

The Na/K/2Cl cotransport system in the avian erythrocyte can be activated by agents that raise intracellular cAMP suggesting the involvement of cAMP-dependent protein kinase (cAMP-PK) in its regulation. Another group of stimuli including fluoride and hypertonicity stimulate cotransport via cAMP-independent means. To further investigate the role of phosphorylation in these processes, we examined the effects of protein kinase inhibitors of 8 (p-Cl-phenylthio)-cAMP (cpt-cAMP), fluoride and hypertonic activation of cotransport in duck red cells, and [3H]bumetanide binding to isolated membranes. Preincubation of cells with the kinase inhibitors K-252a (Ki approximately 1.6 microM) and H-9 (Ki approximately 100 microM) blocked cpt-cAMP activation of bumetanide-sensitive 86Rb influx and bumetanide binding. These inhibitors also led to a rapid deactivation of cotransport and decrease in bumetanide binding when added to cells maximally stimulated by cpt-cAMP. K-252a and H-9 inhibited cotransport activation by cAMP-independent stimuli, but 10-fold higher concentrations were required, implying the involvement of a cAMP-independent phosphorylation process in the mechanism of action of these agents. Removal of stimuli that elevate cAMP leads to a rapid reversal of cotransport indicating the presence of active protein phosphatases in these cells. The protein phosphatase inhibitor okadaic acid (OA, EC50: 630 nM) stimulated both Na/K/2Cl cotransport and bumetanide binding to membranes. As with fluoride and hypertonic stimulation, the OA effect was inhibited only at relatively high concentrations of K-252a. Phosphorylation of the membrane skeletal protein goblin (Mr 230,000) at specific cAMP-dependent sites was used as an in situ marker for the state of activation of cAMP-PK. Goblin phosphorylation at these sites was increased by norepinephrine and cpt-cAMP and rapidly reversed by K-252a and H-9, confirming that both inhibitors do block cAMP-PK activity. While OA markedly increased overall phosphorylation of many erythrocyte membrane proteins, including goblin, it did not affect goblin phosphorylation at specific cAMP-dependent sites. These results implicate a cAMP-independent protein kinase in the mediation of the OA effect on cotransport and bumetanide binding. The bumetanide-binding component of the avian erythrocyte cotransporter, an Mr approximately 150,000 protein that can be photolabeled with the bumetanide analog [3H]4-benzoyl-5-sulfamoyl-3-(3-thenyloxy)-benzoic acid was found to be a phosphoprotein. These results strongly support the hypothesis that phosphorylation and dephosphorylation, possibly of the Na/K/2Cl cotransporter itself, regulates the activity of

Animals↗

Insulin-like growth factor-I supports proliferation of autocrine thymic lymphoma cells with a pre-T cell phenotype.

We have studied the phenotypic characteristics and growth properties of murine T lymphoma cell lines derived from primary x-ray-induced thymic lymphomas at the earliest stage at which they can be detected, and well before spreading to other organs has occurred. These cell lines serve as model systems for the earliest events in T cell lymphoma induction, before tumor cell progression and spreading to other organs. We find that primary x-ray-induced T cell lymphoma lines have phenotypic characteristics of thymic pre-T cells and show no proliferative response to any of the IL tested nor to other hematopoietic growth factors. However, they do proliferate in response to insulin-like growth factor I (IGF-I) and to a small autocrine peptide distinct from IGF-I, which we term lymphoma growth factor. One of the earliest lesions in T cell lymphoma induction may therefore be an inhibition of differentiation at one of several specific points. In its early stages, T lymphoma cell growth may be restricted to an environment where local concentrations of specific growth factors such as IGF-I or lymphoma growth factor are sufficiently high.

Animals↗

Homozygous deletion of the retinoblastoma gene in an acute lymphoblastic leukemia (T) cell line.

Human leukemia cell lines were examined for the status of the retinoblastoma (RB) protein by immunoblotting analysis using antibodies raised against the TrpE-RB fusion protein. One of 16 cell lines examined, the T-cell acute lymphoblastic leukemia (ALL) line HSB-2, lacked the 110-Kd RB protein. Southern blot analysis of genomic DNA extracted from HSB-2 cells showed a large homozygous deletion of the RB gene, stretching from exon 18 beyond exon 27. Northern blot analysis showed multiple, abnormal RB transcripts in HSB-2. A truncated protein (72 Kd) was detected with 35S-methionine labeling but not with 32P-orthophosphate labeling of the HSB-2 cells. The genomic deletion of greater than 85 kb DNA at the RB locus (13q14) was not detectable in the karyotype of the HSB-2 cells. Among the 16 human leukemia cell lines examined for the status of the RB gene, only one, the HSB-2 line, showed an abnormal RB protein. Further study of primary leukemia and lymphoma samples appears to be warranted.

Blotting, Northern↗

Establishment of continuous cultures of T-cell acute lymphoblastic leukemia cells at diagnosis.

We have devised methods facilitating the establishment of continuous cultures of T-cell blasts from patients with acute lymphoblastic leukemia of T-cell type at diagnosis. The cultured cells closely resemble those of the patients at the time of diagnosis with respect to surface markers, karyotype, and T-cell receptor gene rearrangements. Cultured T-cell acute lymphoblastic leukemia (diagnosis) cells (a) are lymphocytes with a convoluted nucleus; (b) have doubling times of 24-48 h; (c) are dependent for growth on interleukin 2; (d) are reverse transcriptase negative; (e) do not form colonies in methyl cellulose; and (f) are clonal with respect to T-cell receptor beta chain rearrangements. Three T-cell acute lymphoblastic leukemia cultures had a normal diploid karyotype, and one had a 6q- deletion which was also present at the time of diagnosis.

Adolescent↗