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Biomedical subjects

M J Weiss

Publications and source records attributed to M J Weiss.

At least 19 recordsLinked to original sources
PubMed1992

Simultaneous assessment of bolus transport and contraction parameters in multiple-swallow investigations.

A better understanding of scintigraphic findings may lead to a wider acceptance of esophageal transit studies. The purpose of this study, therefore, was to correlate standard manometric parameters with the quantitative and qualitative characteristics of liquid and semi-solid bolus transport. Twenty-nine patients were simultaneously investigated with esophageal scintigraphy and manometry. Single-swallow and sum-image data of six consecutive swallows were analyzed. No significant relationship between transit time and the velocity of the peristaltic wave could be identified, which suggests that factors other than peristaltic velocity (e.g., pharyngeal pump) essentially modulate esophageal transit. There was also no linear correlation between esophageal emptying and peristaltic amplitudes. Emptying was normal in patients with amplitudes greater than 30 mmHg and reduced in those with amplitudes less than 30 mmHg. This suggests that a threshold pressure greater than 30 mmHg is necessary to propel a test bolus adequately. Patterns in condensed images have been shown to specifically reflect the events in corresponding manometric recordings. Normal and different pathologic types of peristalsis presented analogous findings in both modalities. Thus, an analysis of the relationship between bolus transport and contraction parameters in simultaneous studies increases understanding of quantitative and qualitative scintigraphic results.

Adult↗
PubMed1991

Enhanced in vitro uptake and retention of 3H-tetraphenylphosphonium by nervous system tumor cells.

Photodynamic therapy is a promising treatment for human brain tumors because of the selective retention of certain compounds by tumor cells. Certain lipophilic cationic compounds, such as tetraphenylphosphonium (TPP), are selectively taken up by a variety of carcinomas. Although preferential retention of TPP has been demonstrated for the breast carcinoma cell line MCF-7, this compound had not been tested previously on cells derived from nervous system tumors. In the present study, tritiated-TPP (3H-TPP) uptake and retention for eight different cell cultures of three histologically different types of nervous system tumors was measured and the data were compared to a positive control (MCF-7) and negative controls (normal African Green monkey kidney epithelium (CV-1) and the normal human fibroblast (WI-38) cell lines). Uptake and retention characteristics could be grouped by specific pathological tumor types, but individual tumor variability was notable. Malignant astrocytoma (grade III/III glioblastoma) and malignant neurofibrosarcoma cells showed preferential uptake and retention of 3H-TPP relative to meningioma cells and normal controls. A clonogenic assay utilizing the cytotoxic lipophilic cationic compound dequalinium showed strong retainers of 3H-TPP to be more susceptible to the effects of dequalinium than weak retainers. These data demonstrate that certain human and experimental animal nervous system tumor cell lines retain lipophilic compounds possessing a delocalized positive charge. Lipophilic cationic compounds may be useful in the intraoperative delineation of tumor margins and in the photodynamic therapy of certain nervous system tumors.

Animals↗
PubMed1990

Serologic tests in the diagnosis of presumed toxoplasmic retinochoroiditis.

We treated three patients who had documented Toxoplasma retinochoroiditis and negative immunofluorescent antibody toxoplasmosis titers (titer less than 1:16), positive Sabin-Feldman dye titers of 1:64, 1:16, and 1:64 in the three patients, respectively, and a positive enzyme-linked immunoassay titer of 1:256 in the one patient tested. In patients with negative immunofluorescent antibody toxoplasmosis titers, we recommend obtaining Sabin-Feldman or enzyme-linked immunoassay titers, or both, before excluding the diagnosis of ocular toxoplasmosis.

Adolescent↗
PubMed1990

Cardiopulmonary resuscitation policies and practices. A statewide nursing home study.

We determined the prevalence of written cardiopulmonary resuscitation policies in North Carolina nursing homes and evaluated their content according to predetermined criteria. Questionnaires were mailed to 236 state-registered facilities. Two hundred nine nursing homes (88.5%) responded to the questionnaire; 83% reported having a written policy, and half (86 nursing homes) provided copies. Nine of ten nursing homes reported that cardiopulmonary resuscitation was performed at their institution, and a similar number (92%) permitted physician orders restricting cardiopulmonary resuscitation. Written policies were systematically compared with 10 model criteria. Policy content varied substantially. More than half of the policies contained provisions for authorization, informed consent, documentation, competency, review, and applicability of do not resuscitate orders. Less than half contained criteria for autonomy, treatment alternatives, dignity and quality of care, and patient identification. Nursing homes that had written policies were newer, larger, and for-profit; had a greater proportion of skilled nursing care beds; and were more likely to have both Medicare and Medicaid certification. The variations in these policies place nursing home residents at risk for having important personal rights limited or ignored. Inclusion of these 10 policy criteria in a comprehensive cardiopulmonary resuscitation policy would represent an important step toward enhancing the quality of decision making by nursing home residents.

Aged↗
PubMed1989

First identification of a gene defect for hypophosphatasia: evidence that alkaline phosphatase acts in skeletal mineralization.

Hypophosphatasia is a heritable disorder characterized by defective osteogenesis and deficient liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. Severe forms of the disease are inherited in an autosomal recessive fashion. We examined cultured skin fibroblasts from twelve patients with severe hypophosphatasia. All were deficient in L/B/K ALP activity, yet produced normal levels of the corresponding mRNA. Sequence analysis of L/B/K ALP cDNA isolated from one of the patient-derived fibroblast lines revealed a point mutation that converted amino acid 162 of mature L/B/K ALP from alanine to threonine. The patient was homozygous and the parents, who are second cousins, heterozygous for this mutation. Introduction of the mutation into an otherwise normal cDNA disrupted the expression of active enzyme, demonstrating that a defect in the L/B/K ALP gene resulted in hypophosphatasia and that the enzyme is, therefore, essential for normal skeletal mineralization.

Alkaline Phosphatase↗
PubMed1989

Analysis of liver/bone/kidney alkaline phosphatase mRNA, DNA, and enzymatic activity in cultured skin fibroblasts from 14 unrelated patients with severe hypophosphatasia.

Hypophosphatasia is a heritable disorder characterized by defective bone mineralization and a deficiency of liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity in serum and tissues. Severe forms of the disease, which are generally lethal in infancy, are inherited in an autosomal recessive fashion. The gene defects that produce hypophosphatasia are poorly understood, but many are likely to occur at the L/B/K ALP locus. To investigate these gene defects, we analyzed L/B/K ALP DNA, RNA, and enzyme activity in cultured dermal fibroblasts from 14 patients with perinatal or infantile hypophosphatasia and from 12 normal individuals. Southern blot analyses of the L/B/K ALP genes from patients and controls revealed identical restriction patterns. Control fibroblast ALP activity correlated with the corresponding L/B/K ALP mRNA levels estimated by blot hybridization analysis and densitometry (r = .94, P less than .0001). In contrast, fibroblasts from the hypophosphatasia patients were deficient in ALP enzyme activity but expressed apparently full-sized L/B/K ALP mRNA at normal levels. Bone specimens from one of the patients were examined and found to be deficient in histochemical ALP but contained immunologic cross-reactive material detected by anti-human liver ALP antiserum. Our results demonstrate that the deficiency of ALP activity in fibroblasts from 14 patients with severe hypophosphatasia is not due to decreased steady-state levels of the corresponding mRNA. The presence of enzymatically inactive L/B/K ALP protein in one of these patients is consistent with a point mutation or small in-frame deletion in the coding region of L/B/K ALP gene.

Alkaline Phosphatase↗
PubMed1988

Sequence and characterization of the human intestinal alkaline phosphatase gene.

At least four genes encode the human alkaline phosphatases (ALPs). The genes encoding three of these proteins (intestinal, placental, and placental-like ALPs), are linked on the long arm of chromosome 2, while the fourth gene (encoding liver/bone/kidney ALP) is located on chromosome 1. One of the linked genes, intestinal alkaline phosphatase, has been isolated on two overlapping phage clones and sequenced in its entirety. The gene is composed of 11 exons interrupted by 10 introns. Introns in intestinal, placental, and liver/bone/kidney ALPs occur at analogous positions (see accompanying articles), confirming that these genes arose from a single ancestral ALP gene. Multiple intestinal ALP mRNA species can be detected in RNA isolated from adult and fetal intestine and from cell line RNAs. In cell line RNA, the various species are the result of differential use of at least three of the four polyadenylation signals present in the intestinal ALP gene. A 125-base pair fragment located 5' to the first exon can function as a promoter in mammalian cells. This region contains two putative transcription signals, a TATA-like sequence and a consensus binding site for the transcription factor Sp1.

Alkaline Phosphatase↗
PubMed1988

Structure of the human liver/bone/kidney alkaline phosphatase gene.

In man, there are multiple forms of alkaline phosphatase encoded by at least three homologous genes: placental, intestinal, and liver/bone/kidney. This report describes the characterization of the human liver/bone/kidney alkaline phosphatase locus. The gene appears to exist as a single copy in the haploid genome and is comprised of 12 exons distributed over more than 50 kilobases. In liver, kidney, SAOS-2 human osteosarcoma cells, and cultured fibroblasts, there is a single major start for transcription situated about 25 nucleotides downstream of an A/T-rich motif. The promoter region is extremely G/C-rich, is relatively abundant in the dinucleotide CpG, and contains four copies of the consensus sequence for SP1 binding (GGGCGG). The liver/bone/kidney alkaline phosphatase gene is at least five times larger than the intestinal and placental alkaline phosphatase genes, mainly due to intron size differences. Intron-exon junctions occur at analogous positions in all three genes, but there is an extra non-coding exon at the 5' end of the liver/bone/kidney alkaline phosphatase gene. The relevance of our findings with respect to the evolution of the human alkaline phosphatase multigene family is discussed.

Alkaline Phosphatase↗
PubMed1988

Regional assignment of the gene for human liver/bone/kidney alkaline phosphatase to chromosome 1p36.1-p34.

We have used three different methods to map the human liver/bone/kidney alkaline phosphatase (ALPL) locus: (1) Southern blot analysis of DNA derived from a panel of human-rodent somatic cell hybrids; (2) in situ hybridization to human chromosomes; and (3) genetic linkage analysis. Our results indicate that the ALPL locus maps to human chromosome bands 1p36.1-p34 and is genetically linked to the Rh (maximum lod score of 15.66 at a recombination value of 0.10) and fucosidase A (maximum lod score of 8.24 at a recombination value of 0.02) loci. These results, combined with restriction fragment length polymorphisms identified by ALPL DNA probes, provide a useful marker for gene mapping studies involving the short arm of chromosome 1. In addition, our results help to elucidate further the structure and evolution of the human alkaline phosphatase multigene enzyme family.

Alkaline Phosphatase↗
PubMed1988

Levobunolol and betaxolol. A double-masked controlled comparison of efficacy and safety in patients with elevated intraocular pressure.

In a double-masked, randomized, controlled clinical trial, the authors evaluated the ocular hypotensive efficacy of twice-daily treatment with levobunolol (0.25 and 0.5%) and betaxolol (0.5%) in 85 patients with open-angle glaucoma or ocular hypertension. During the 3-month study, intraocular pressure (IOP) reductions in the two levobunolol groups were significantly greater than in the betaxolol group. From a mean baseline IOP of approximately 25 mmHg, overall mean reductions were 6.2 and 6.0 mmHg for the 0.25 and 0.5% levobunolol groups, respectively, and 3.7 mmHg for the betaxolol group. No clinically or statistically significant among-group differences were noted in the systemic safety variables evaluated. These data suggest that although all three treatments are effective, levobunolol provides a greater reduction in IOP than betaxolol.

Betaxolol↗
PubMed1988

A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia.

Hypophosphatasia is an inherited disorder characterized by defective bone mineralization and a deficiency of serum and tissue liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. Clinical severity is variable, ranging from death in utero (due to severe rickets) to pathologic fractures first presenting in adult life. Affected siblings, however, are phenotypically similar. Severe forms of the disease are inherited in an autosomal recessive fashion; heterozygotes often show reduced serum ALP activity. The specific gene defects in hypophosphatasia are unknown but are thought to occur either at the L/B/K ALP locus or within another gene that regulates L/B/K ALP expression. We used the polymerase chain reaction to examine L/B/K ALP cDNA from a patient with a perinatal (lethal) form of the disease. We observed a guanine-to-adenine transition in nucleotide 711 of the cDNA that converts alanine-162 of the mature enzyme to threonine. The affected individual, whose parents are second cousins, is homozygous for the mutant allele. Introduction of this mutation into an otherwise normal cDNA by site-directed mutagenesis abolishes the expression of active enzyme, demonstrating that a defect in the L/B/K ALP gene results in hypophosphatasia and that the enzyme is, therefore, essential for normal skeletal mineralization.

Alkaline Phosphatase↗
PubMed1988

Newborn response to auditory stimulus discrepancy.

Newborns were assessed for their recovery of head turning toward laterally presented auditory stimuli (titi) that varied from a familiar standard on 1 of 5 levels of fundamental frequency. Following habituation to repeated standard trials, newborns recovered to 14% and 21%, but not to 0%, 7%, or 28% discrepancies, indicating that recovery was a quadratic function of the degree of stimulus-schema discrepancy. Moreover, newborns reliably turned away from the standard stimulus during posthabituation no-change control trials, indicating that the neural network associated with that stimulus was not fatigued. Infants in every condition showed recovery of head turning to a novel posttest stimulus (papa). These data are interpreted with a dual processing model postulated to include both reflexive (context-independent) orientation and stimulus-schema comparison process (context-dependent) orientation.

Arousal↗
PubMed1987

Dequalinium, a topical antimicrobial agent, displays anticarcinoma activity based on selective mitochondrial accumulation.

Positively charged lipophilic compounds, such as rhodamine 123, localize in mitochondria and are selectively accumulated and retained by carcinoma cells. It has been suggested that this phenotype may be exploited for selective killing of carcinoma cells by lipophilic cations. Here we report that doubly positively charged dequalinium, which has been used for 30 years as an antimicrobial agent in over-the-counter mouthwashes, lozenges, ointments, and paints, exhibits significant anticarcinoma activity. Dequalinium is more effective than seven of eight established anticancer drugs in prolonging the survival of mice with intraperitoneally implanted mouse bladder carcinoma MB49. Dequalinium also inhibits the growth of subcutaneously implanted human colon carcinoma CX-1 in nude mice and recurrent rat colon carcinoma W163 in rats. Lipophilic cationic compounds, such as dequalinium, could comprise a unique class of anticarcinoma agents.

Animals↗
PubMed1987

Nucleotide and amino acid sequences of human intestinal alkaline phosphatase: close homology to placental alkaline phosphatase.

A cDNA clone for human adult intestinal alkaline phosphatase (ALP) [orthophosphoric-monoester phosphohydrolase (alkaline optimum); EC 3.1.3.1] was isolated from a lambda gt11 expression library. The cDNA insert of this clone is 2513 base pairs in length and contains an open reading frame that encodes a 528-amino acid polypeptide. This deduced polypeptide contains the first 40 amino acids of human intestinal ALP, as determined by direct protein sequencing. Intestinal ALP shows 86.5% amino acid identity to placental (type 1) ALP and 56.6% amino acid identity to liver/bone/kidney ALP. In the 3'-untranslated regions, intestinal and placental ALP cDNAs are 73.5% identical (excluding gaps). The evolution of this multigene enzyme family is discussed.

Alkaline Phosphatase↗
PubMed1987

Cloning and characterization of platelet factor 4 cDNA derived from a human erythroleukemic cell line.

We report the isolation of a platelet factor 4 (PF4) cDNA clone from a lambda gt11 expression cDNA library which was derived from a human erythroleukemic (HEL) cell line. The sequence of the DNA insert includes the 3'-untranslated region, the entire amino acid coding region for the mature PF4 protein, and a 5' region containing coding information for an additional 18 amino acids. In addition, supplemental genomic DNA sequencing shows that the full-length leader sequence is 30 amino acids long plus an initial methionine and codes for a hydrophobic signal-like sequence which is probably involved in transmembrane transport. A single species mRNA of approximately 800 nucleotides was detected on blots of HEL cell poly(A) + RNA using a labeled PF4 cDNA probe. The human PF4 leader sequence shares some DNA, but no amino acid, homology with the 15 amino acids at the N-terminus of mature bovine PF4, suggesting rapid divergence in this region of PF4 between these two species. Sequence comparison of the coding regions of mature PF4 and gamma IP-10, a protein induced in a variety of cells following treatment with gamma-interferon, shows a corrected divergence of 76%. The divergence of a common ancestor protein into PF4 and gamma IP-10 may have accompanied the development of sophisticated immune and coagulation systems in vertebrates. The availability of cDNA and genomic DNA information for these genes in other species will be useful in studying the evolution of the coagulation and immune systems.

Amino Acid Sequence↗